NCBI Conserved Domain Search

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 208.27 E-value: 1.17e-62

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  319 QFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQAL 398
Cdd:cd05726     1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQAL 80

                          90
                  ....*....|....*...
gi 568997560  399 TVAGSILAKAQLEVTDVL 416
Cdd:cd05726    81 NVAGSILAKAQLEVTDVL 98

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 204.32 E-value: 2.54e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRMLLPSGSLFFLRIVHGRRSKPDEGSYVC 110
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRVVHGRKGRSDEGVYVC 80

                          90
                  ....*....|....*....
gi 568997560  111 VARNYLGEAVSRNASLEVA 129
Cdd:cd07693    81 VAHNSLGEAVSRNASLEVA 99

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 152.65 E-value: 2.35e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  423 IILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd20952     1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80


                  ....*..
gi 568997560  503 WSAVLDV 509
Cdd:cd20952    81 WSAVLDV 87

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 135.22 E-value: 2.48e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  136 RQNPTDVVVAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERISIR-GGKLMISNTRKSDAGMYTCVGTNMVGERDS 214
Cdd:cd05724     1 RVEPSDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERVRIVdDGNLLIAEARKSDEGTYKCVATNMVGERES 80


                  ....*..
gi 568997560  215 DPAELTV 221
Cdd:cd05724    81 RAARLSV 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 132.13 E-value: 2.92e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  228 LRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASAT 307
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                  ...
gi 568997560  308 LTV 310
Cdd:cd05725    81 LTV 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 108.88 E-value: 5.05e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRGRYDIK---DDYTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrSSDRFKVTyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 568997560   301 KVEASATLTV 310
Cdd:pfam07679   81 EAEASAELTV 90

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 93.31 E-value: 1.69e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDprsHRMLLPSGSLFFLRIVHGRRSKPDEGSYVCVARNY- 115
Cdd:cd05722     8 PSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDE---RRQQLPNGSLLITSVVHSKHNKPDEGFYQCVAQNEs 84

                          90
                  ....*....|...
gi 568997560  116 LGEAVSRNASLEV 128
Cdd:cd05722    85 LGSIVSRTARVTV 97

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 83.60 E-value: 3.21e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDG-TALLKCKATGEPLPVISWLKEGFTFLGRDPRATIqDQGTLQIKNLRISDTGTYTCVATSSSGE 500
Cdd:cd20978     1 PKFIQKPEKNVVVKGGqDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATV-EDGTLTIINVQPEDTGYYGCVATNEIGD 79


                  ....*....
gi 568997560  501 TSWSAVLDV 509
Cdd:cd20978    80 IYTETLLHV 88

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 82.93 E-value: 6.63e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  526 PGPPSKPQVTDVSKNSVTLSWQPGTPGVLPASAYIIEaFSQSVSNSWQTVANH-VKTTLYTVRGLRPNTIYLFMVRAINP 604
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVE-YREKGSGDWKEVEVTpGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....*
gi 568997560  605 QGLSDPSPmSDPVRT 619
Cdd:cd00063    80 GGESPPSE-SVTVTT 93

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 91.22 E-value: 1.93e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  487 TGTYTCVATSSSGETSWSAVLDVTesgatisknyDMNDLPGPPSKPQVTDVSKNSVTLSWQPGTpgVLPASAYIIEAfSQ 566
Cdd:COG3401   204 TYYYRVAATDTGGESAPSNEVSVT----------TPTTPPSAPTGLTATADTPGSVTLSWDPVT--ESDATGYRVYR-SN 270

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  567 SVSNSWQTVANhVKTTLYTVRGLRPNTIYLFMVRAINPQGLsdPSPMSDPVRTQ-DISPPA--QGVDHrqvqkelgdvvv 643
Cdd:COG3401   271 SGDGPFTKVAT-VTTTSYTDTGLTNGTTYYYRVTAVDAAGN--ESAPSNVVSVTtDLTPPAapSGLTA------------ 335

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  644 rlhnpVVLTPTTVQVTWTvDRQPQFIQGYRVmYRQTSGlqaSTVWQNLdAKVPTERSAVLVNLKKGVTYEIKVRPYFNEf 723
Cdd:COG3401   336 -----TAVGSSSITLSWT-ASSDADVTGYNV-YRSTSG---GGTYTKI-AETVTTTSYTDTGLTPGTTYYYKVTAVDAA- 403

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  724 qGMDSE-SKTVRTTEEAPSAPPQS-----VTVLTVGSHNSTSISVSWDPPPADHQNGIIQEYKIWCLGNETRFHINKT-- 795
Cdd:COG3401   404 -GNESApSEEVSATTASAASGESLtasvdAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATtt 482

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  796 -VDAAIRSVVIGGLFPGIQYrVEVAASTSAGVGVKSEPQPIIIGGrNEVVITENNNSITEQITDV 859
Cdd:COG3401   483 dTTTANLSVTTGSLVGGSGA-SSVTNSVSVIGASAAAAVGGAPDG-TPNVTGASPVTVGASTGDV 545

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 80.63 E-value: 3.52e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    428 PINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQG---TLQIKNLRISDTGTYTCVATSSSGETSWS 504
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 568997560    505 AVLDV 509
Cdd:smart00410   81 TTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 80.76 E-value: 4.18e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCSVSPTGD---LTITNIQRSDAGYYI 394
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG--------QPLRSSDRFKVTYEGGtytLTISNVQPDDSGKYT 72

                           90
                   ....*....|....*...
gi 568997560   395 CQALTVAGSILAKAQLEV 412
Cdd:pfam07679   73 CVATNSAGEAEASAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 79.22 E-value: 1.17e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDkddprSHRMLLPSGSLFFLRIvhgRRSKP-DEGSYV 109
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSS-----DRFKVTYEGGTYTLTI---SNVQPdDSGKYT 72

                           90
                   ....*....|....*....
gi 568997560   110 CVARNYLGEAVSRnASLEV 128
Cdd:pfam07679   73 CVATNSAGEAEAS-AELTV 90

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 77.16 E-value: 5.60e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    231 PINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL--PRGRYDI---KDDYTLRIKKAMSTDEGTYVCIAENRVGKVEAS 305
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaESGRFSVsrsGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 568997560    306 ATLTV 310
Cdd:smart00410   81 TTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 75.29 E-value: 1.93e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdKDDPRSHRMLLPSGSLFFLRIVhgrrSKPDEGSYV 109
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI---SSGSTRSRSLSGSNSTLTISNV----TRSDAGTYT 73


                   ....*
gi 568997560   110 CVARN 114
Cdd:pfam13927   74 CVASN 78

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 75.23 E-value: 3.11e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    324 PRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPnqpqqpnSRCSVSPTGD---LTITNIQRSDAGYYICQALTV 400
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES-------GRFSVSRSGStstLTISNVTPEDSGTYTCAATNS 73

                            90
                    ....*....|..
gi 568997560    401 AGSILAKAQLEV 412
Cdd:smart00410   74 SGSASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 74.96 E-value: 3.75e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    526 PGPPSKPQVTDVSKNSVTLSWQPGTPGvlPASAYIIE--AFSQSVSNSWQTVANHVKTTLYTVRGLRPNTIYLFMVRAIN 603
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDD--GITGYIVGyrVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 568997560    604 PQGLS 608
Cdd:smart00060   79 GAGEG 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 74.52 E-value: 4.21e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQ 396
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGE-----PISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75


                   .
gi 568997560   397 A 397
Cdd:pfam13927   76 A 76

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 74.15 E-value: 6.43e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  228 LRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKD-DADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASA 306
Cdd:cd05723     1 LKKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNgDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASA 80


                  ....
gi 568997560  307 TLTV 310
Cdd:cd05723    81 QLII 84

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 73.50 E-value: 1.45e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKD-GERVETDKD---DPRSHrmLLPSGSLFFLRIvhgrrSKPDE 105
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAtGSTPGEYKDllyDPNVR--ILPNGTLVFGHV-----QKENE 73

                          90       100
                  ....*....|....*....|...
gi 568997560  106 GSYVCVARNYLGEAVSRNASLEV 128
Cdd:cd20954    74 GHYLCEAKNGIGSGLSKVIFLKV 96

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 72.81 E-value: 1.61e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  425 LQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGftflGRDP--RATIQDQGTLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKED----GELPkgRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 568997560  503 WSAVLDV 509
Cdd:cd05725    77 ASATLTV 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 72.29 E-value: 3.52e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRI-DDKEERISIRGGK--LMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTV-TGTPDPEVSWFKDGQPLrSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVATNSAGE 81

                           90
                   ....*....|
gi 568997560   212 RDSDpAELTV 221
Cdd:pfam07679   82 AEAS-AELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 72.29 E-value: 3.77e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDQG---TLQIKNLRISDTGTYTCVATSSS 498
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 568997560   499 GETSWSAVLDV 509
Cdd:pfam07679   80 GEAEASAELTV 90

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 80.05 E-value: 6.50e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  468 RATIQDQGTLQI---KNLRISDTG-------TYTCVATSSSGETS-WSAVLDVTESGAtisknydmndLPGPPSKPQVTD 536
Cdd:COG3401   268 RSNSGDGPFTKVatvTTTSYTDTGltngttyYYRVTAVDAAGNESaPSNVVSVTTDLT----------PPAAPSGLTATA 337

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  537 VSKNSVTLSWQPGTPGvlPASAYIIEAfSQSVSNSWQTVANHVKTTLYTVRGLRPNTIYLFMVRAINPQGLSdpSPMSDP 616
Cdd:COG3401   338 VGSSSITLSWTASSDA--DVTGYNVYR-STSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNE--SAPSEE 412

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  617 VRTQDISPPAQGVDHRQVQKELGDVVVRLHNPVVLTPTTVQVTWTVDrqPQFIQGYRVMYRQTSGLQASTVWQNLDAKVP 696
Cdd:COG3401   413 VSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLA--DGGDTGNAVPFTTTSSTVTATTTDTTTANLS 490

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  697 TER-SAVLVNLKKGVTYEIKVRPYFNEFQGM----DSESKTVRTTEEAPSAPPQSVTVLTVGSHNSTSISVSW 764
Cdd:COG3401   491 VTTgSLVGGSGASSVTNSVSVIGASAAAAVGgapdGTPNVTGASPVTVGASTGDVLITDLVSLTTSASSSVSG 563

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 70.89 E-value: 1.02e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  323 RPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfpnqpQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAG 402
Cdd:cd05725     3 RPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG---------ELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVG 73

                          90
                  ....*....|
gi 568997560  403 SILAKAQLEV 412
Cdd:cd05725    74 KIEASATLTV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.29 E-value: 1.09e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560   421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEG--FTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVAT 495
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 70.51 E-value: 1.23e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   35 EHPSDVIVSKGEPTTLNCKA-EGRPTPTIEWYKDGERVetdkDDPRSHRMLLPSGSLFflrIVHGRRSkpDEGSYVCVAR 113
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPL----NLDNERVRIVDDGNLL---IAEARKS--DEGTYKCVAT 72

                          90
                  ....*....|....*
gi 568997560  114 NYLGEAVSRNASLEV 128
Cdd:cd05724    73 NMVGERESRAARLSV 87

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 70.50 E-value: 1.31e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEE-EAVEFRCQVQGDPQPTVRWKKDDADL--PRGRYDIkDDYTLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd20978     1 PKFIQKPEKNVVVKGgQDVTLPCQVTGVPQPKITWLHNGKPLqgPMERATV-EDGTLTIINVQPEDTGYYGCVATNEIGD 79


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd20978    80 IYTETLLHV 88

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 70.60 E-value: 1.45e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISI-RGGKLMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQA-TGEPVPTISWLKDGVPLLGKDERITTlENGSLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 69.67 E-value: 1.86e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  242 VEFRCQVQGDPQPTVRWKKDDADLP----RGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASAT 307
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPpssrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 69.96 E-value: 2.08e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNllFPNQPQQpnsRCSVSPTGD-LTITNIQRSDAGYYICQAL 398
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTD--FPAARER---RMHVMPEDDvFFIVDVKIEDTGVYSCTAQ 76

                          90
                  ....*....|....
gi 568997560  399 TVAGSILAKAQLEV 412
Cdd:cd05763    77 NSAGSISANATLTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 68.36 E-value: 6.08e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560   224 RPTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLP----RGRYDIKDDYTLRIKKAMSTDEGTYVCIAEN 297
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISsgstRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 68.29 E-value: 7.46e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   33 IVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETdkDDPRShrMLLPSGSlffLRIVHGRRSkpDEGSYVCVA 112
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLG--KDERI--TTLENGS---LQIKGAEKS--DTGEYTCVA 72

                          90
                  ....*....|....*.
gi 568997560  113 RNYLGEAVSRnASLEV 128
Cdd:cd20952    73 LNLSGEATWS-AVLDV 87

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 68.21 E-value: 8.38e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   527 GPPSKPQVTDVSKNSVTLSWQPGTPGVLPASAYIIEAFSQSVSNSWQTVANHVKTTLYTVRGLRPNTIYLFMVRAINPQG 606
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 568997560   607 LSDPS 611
Cdd:pfam00041   81 EGPPS 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 67.35 E-value: 1.11e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  439 ALLKCKATGEPLPVISWLKEGFTFL--GRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAV 506
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPpsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 67.87 E-value: 1.41e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  433 LAVDGTALLKCKATGEPLPVISWlKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISW-SKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 67.15 E-value: 1.80e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    139 PTDVVVAAGEPAILECQPPrGHPEPTIYWKKDKVRIDDKEERISIRGGK----LMISNTRKSDAGMYTCVGTNMVGERDS 214
Cdd:smart00410    1 PPSVTVKEGESVTLSCEAS-GSPPPEVTWYKQGGKLLAESGRFSVSRSGststLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*..
gi 568997560    215 dPAELTV 221
Cdd:smart00410   80 -GTTLTV 85

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 66.71 E-value: 3.46e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  134 DFRQNPTD--VVVAAGEPAILECQPpRGHPEPTIYWKKDKvRIDDKEERISI-RGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd04969     2 DFELNPVKkkILAAKGGDVIIECKP-KASPKPTISWSKGT-ELLTNSSRICIlPDGSLKIKNVTKSDEGKYTCFAVNFFG 79


                  ....
gi 568997560  211 ERDS 214
Cdd:cd04969    80 KANS 83

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 66.37 E-value: 3.86e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCS--VSPTG--DLTITNIQRSDAGYY 393
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNG--------KPVRPDSAHKmlVRENGrhSLIIEPVTKRDAGIY 72

                          90
                  ....*....|....*....
gi 568997560  394 ICQALTVAGSILAKAQLEV 412
Cdd:cd05744    73 TCIARNRAGENSFNAELVV 91

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 65.99 E-value: 4.74e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560     37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRmllpSGSLFFLRIVHGRRSkpDEGSYVCVARNYL 116
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSR----SGSTSTLTISNVTPE--DSGTYTCAATNSS 74

                            90
                    ....*....|..
gi 568997560    117 GEaVSRNASLEV 128
Cdd:smart00410   75 GS-ASSGTTLTV 85

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 65.94 E-value: 6.39e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRP--RDQIVAQGRTVTFPCETKGNPQPAVFWQKeGSQNLlfpnqpqQPNSRCSVSPTGDLTITNIQRSDAGYYIC 395
Cdd:cd04969     1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSK-GTELL-------TNSSRICILPDGSLKIKNVTKSDEGKYTC 72

                          90
                  ....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEV 412
Cdd:cd04969    73 FAVNFFGKANSTGSLSV 89

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 65.51 E-value: 7.00e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  233 NQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYdIKDDY--TLRIKKAMSTDEGTYVCIAENRVGKveASATLTV 310
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRT-KFENFnkTLKIENVSEADSGEYQCTASNTMGS--ARHTISV 80


                  ...
gi 568997560  311 RVR 313
Cdd:cd05731    81 TVE 83

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 65.73 E-value: 7.29e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIV---SKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprsHRMLLPSGSLfflrIVHGRRSKPDEGS 107
Cdd:cd05848     2 PVFVQEPDDAIFptdSDEKKVILNCEARGNPVPTYRWLRNGTEIDTESD----YRYSLIDGNL----IISNPSEVKDSGR 73

                          90       100
                  ....*....|....*....|..
gi 568997560  108 YVCVARNYLGEAVSRNASLEVA 129
Cdd:cd05848    74 YQCLATNSIGSILSREALLQFA 95

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 65.61 E-value: 7.70e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  137 QNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIR--GGKLMISNTRKSDAGMYTCVGTNMVGERDS 214
Cdd:cd20970     7 QPSFTVTAREGENATFMCRA-EGSPEPEISWTRNGNLIIEFNTRYIVRenGTTLTIRNIRRSDMGIYLCIASNGVPGSVE 85


                  ....*..
gi 568997560  215 DPAELTV 221
Cdd:cd20970    86 KRITLQV 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 65.50 E-value: 7.72e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  426 QGPINQTLAVDGTALLKCKA-TGEPLPVISWLKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGE 500
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 65.60 E-value: 7.97e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  227 FLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRG--RYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEA 304
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKdeRITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81


                  ....*.
gi 568997560  305 SATLTV 310
Cdd:cd20952    82 SAVLDV 87

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 65.41 E-value: 1.08e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEgsqnllFPNQPQQ-----PNSRCSVSPTGDLTITNIQRSDAG 391
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKA------TGSTPGEykdllYDPNVRILPNGTLVFGHVQKENEG 74

                          90
                  ....*....|....*.
gi 568997560  392 YYICQALTVAGSILAK 407
Cdd:cd20954    75 HYLCEAKNGIGSGLSK 90

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 65.27 E-value: 1.22e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTfLGRDPRATIQDQGT--------LQIKNLRISDTGTYTC 492
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFP-IPESPRFRVGDYVTsdgdvvsyVNISSVRVEDGGEYTC 79

                          90
                  ....*....|....*..
gi 568997560  493 VATSSSGETSWSAVLDV 509
Cdd:cd20956    80 TATNDVGSVSHSARINV 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 64.51 E-value: 1.30e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560   135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEER---ISIRGGKLMISNTRKSDAGMYTCVGTN 207
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRsrsLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 64.27 E-value: 1.49e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560   49 TLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHrmLLPSGSLFFLRIvhgrrSKPDEGSYVCVARNYLGEAVSRNA 124
Cdd:cd00096     2 TLTCSASGNPPPTITWYKNGKPLPPSSRDSRRS--ELGNGTLTISNV-----TLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 64.75 E-value: 1.71e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKD----DADLPRGRYDIKDDY---TLRIKKAMSTDEGTYVCIAEN 297
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNgvpiDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 568997560  298 RVGKVEASATLTVR 311
Cdd:cd20951    81 IHGEASSSASVVVE 94

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 64.40 E-value: 1.92e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEA--VEFRCQVQGDPQPTVRWKKDDADLPR-GRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd04969     1 PDFELNPVKKKILAAKGgdVIIECKPKASPKPTISWSKGTELLTNsSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd04969    81 ANSTGSLSV 89

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 63.76 E-value: 2.84e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  235 VVLEEEAVEFRCQVQGDPQPTVRWKKDDADL---PRGRYDIKDDYT-LRIKKAMSTDEGTYVCIAENRVGkvEASATLTV 310
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPLketGRVQIETTASSTsLVIKNAKRSDSGKYTLTLKNSAG--EKSATINV 80


                  ..
gi 568997560  311 RV 312
Cdd:cd05748    81 KV 82

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 64.05 E-value: 3.22e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  744 PQSVTVLTVGSHNSTSISVSWDPPPADhqNGIIQEYKI-WCLGNETRFHINKTVDAAIRSVVIGGLFPGIQYRVEVAAST 822
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVeYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|....
gi 568997560  823 SAGVGVKSEPQPII 836
Cdd:cd00063    79 GGGESPPSESVTVT 92

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 63.42 E-value: 3.23e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  331 QGRTVTFPCETKGNPQPAVFWQKEGSQNLLfpnqpqqpNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGSILAKAQL 410
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSV--------DRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQL 72


                  ..
gi 568997560  411 EV 412
Cdd:cd05745    73 TV 74

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 64.07 E-value: 3.29e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  230 RPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRG--RYDIKDD-YTLRIKKAMSTDEGTYVCIAENRV-GKVEAS 305
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFntRYIVRENgTTLTIRNIRRSDMGIYLCIASNGVpGSVEKR 87


                  ....*
gi 568997560  306 ATLTV 310
Cdd:cd20970    88 ITLQV 92

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 63.34 E-value: 5.94e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQK--EGSQNLLFpnQPQQPNSRCSVSPTGDLTITNIQRSDAGYYIC 395
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvPGKENLIM--RPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTC 78

                          90
                  ....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEV 412
Cdd:cd05765    79 TARNSGGLLRANFPLSV 95

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 70.42 E-value: 6.03e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  426 QGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSA 505
Cdd:COG3401    33 GKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPTATGLTTLTGSGSVGGATNTGLT 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  506 VLDVTESGATISKNYDMN-DLPGPPSKPQVTDVSKNSVTLSWQPGTPGVLPASAYIIEAFSQSVSNSWQTVANHVKTTLY 584
Cdd:COG3401   113 SSDEVPSPAVGTATTATAvAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTL 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  585 TVRGLR--PNTIYLFMVRAINPQGLSDPSPMSDPvrTQDISPPAQGvdhrqvqkelGDVVVrlhnpVVLTPTTVQVTWTv 662
Cdd:COG3401   193 VDGGGDiePGTTYYYRVAATDTGGESAPSNEVSV--TTPTTPPSAP----------TGLTA-----TADTPGSVTLSWD- 254

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  663 DRQPQFIQGYRVmYRQTSGLQASTvwqnldaKVPTERSAVLV--NLKKGVTYEIKVRPY-FNEFQGMDSESKTVRTTEEA 739
Cdd:COG3401   255 PVTESDATGYRV-YRSNSGDGPFT-------KVATVTTTSYTdtGLTNGTTYYYRVTAVdAAGNESAPSNVVSVTTDLTP 326

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  740 PSAPpqsvTVLTVGSHNSTSISVSWDPPPadhqNGIIQEYKIW-CLGNETRFH-INKTVDAAirSVVIGGLFPGIQYRVE 817
Cdd:COG3401   327 PAAP----SGLTATAVGSSSITLSWTASS----DADVTGYNVYrSTSGGGTYTkIAETVTTT--SYTDTGLTPGTTYYYK 396

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  818 VAASTSAgvGVKSEPQPIIIGGRNEVVITEnnnsITEQITDVVKQPAFIAGIGGACWVILMGFSIWLYWRRKKRKGLSNY 897
Cdd:COG3401   397 VTAVDAA--GNESAPSEEVSATTASAASGE----SLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPF 470

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  898 AVTFQRGDGGLMSNGsrpgllNAGDPNYPWLADSWPATSLPVNNSNSGPNEIGNFGRG--DVLPPVPGQGDKTATMLSDG 975
Cdd:COG3401   471 TTTSSTVTATTTDTT------TANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGapDGTPNVTGASPVTVGASTGD 544

                         570       580       590
                  ....*....|....*....|....*....|....*.
gi 568997560  976 AIYSSIDFTTKTTYNSSSQITQATPYATTQILHSNS 1011
Cdd:COG3401   545 VLITDLVSLTTSASSSVSGAGLGSGNLYLITTLGGS 580

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 62.35 E-value: 6.44e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  335 VTFPCETKGNPQPAVFWQKEGSqnllfPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAG 402
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGK-----PLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 63.28 E-value: 7.19e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQ-KEGSQNLLFpNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYIC 395
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKhSKGSGVPQF-QHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLC 79

                          90
                  ....*....|...
gi 568997560  396 QALTVAGSILAKA 408
Cdd:cd05734    80 KVSNDVGADISKS 92

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 62.41 E-value: 9.51e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGR-TVTFPCETKGNPQPAVFWQKEGsqnllfpNQPQQPNSRCSVSpTGDLTITNIQRSDAGYYICQ 396
Cdd:cd20978     1 PKFIQKPEKNVVVKGGqDVTLPCQVTGVPQPKITWLHNG-------KPLQGPMERATVE-DGTLTIINVQPEDTGYYGCV 72

                          90
                  ....*....|....*.
gi 568997560  397 ALTVAGSILAKAQLEV 412
Cdd:cd20978    73 ATNEIGDIYTETLLHV 88

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 61.74 E-value: 1.72e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLfpnqpqqPNSRCSVSPTGDLTITNIQRSDAGYYICQALT 399
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLG-------KDERITTLENGSLQIKGAEKSDTGEYTCVALN 74

                          90
                  ....*....|...
gi 568997560  400 VAGSILAKAQLEV 412
Cdd:cd20952    75 LSGEATWSAVLDV 87

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 61.89 E-value: 1.74e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRA-TIQDQGT-LQIKNLRISDTGTYTCVATSSSG 499
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQlTLIANGSeLHISNVRYEDTGAYTCIAKNEGG 80

                          90
                  ....*....|...
gi 568997560  500 ETSWSAVLDVTES 512
Cdd:cd05736    81 VDEDISSLFVEDS 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 61.66 E-value: 1.76e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   743 PPQSVTVLTVgshNSTSISVSWDPPPadHQNGIIQEYKI-WCLGNETRFHINKTVDAAIRSVVIGGLFPGIQYRVEVAAS 821
Cdd:pfam00041    2 APSNLTVTDV---TSTSLTVSWTPPP--DGNGPITGYEVeYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 568997560   822 TSAGVGVKS 830
Cdd:pfam00041   77 NGGGEGPPS 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 60.81 E-value: 1.98e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  150 AILECQPpRGHPEPTIYWKKDKVRIDDK---EERISIRGGKLMISNTRKSDAGMYTCVGTNMVGERDS 214
Cdd:cd00096     1 VTLTCSA-SGNPPPTITWYKNGKPLPPSsrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 61.74 E-value: 2.08e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRGRYDIKDD----YTLRIKKAMSTDEGTYVCIAENRV 299
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrPDSAHKMLVRengrHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 568997560  300 GKVEASATLTV 310
Cdd:cd05744    81 GENSFNAELVV 91

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 61.37 E-value: 2.20e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  323 RPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpNQPQQPNSRCSVSPTGD-LTITNIQRSDAGYYICQALT-V 400
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNG-------NLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgV 80

                          90
                  ....*....|..
gi 568997560  401 AGSILAKAQLEV 412
Cdd:cd20970    81 PGSVEKRITLQV 92

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 60.71 E-value: 3.35e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    740 PSAPPQsvtvLTVGSHNSTSISVSWDPPPADHQNGIIQEYKIWCLGNETRFHiNKTVDAAIRSVVIGGLFPGIQYRVEVA 819
Cdd:smart00060    1 PSPPSN----LRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWK-EVNVTPSSTSYTLTGLKPGTEYEFRVR 75


                    ....*...
gi 568997560    820 ASTSAGVG 827
Cdd:smart00060   76 AVNGAGEG 83

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 60.88 E-value: 3.47e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEH-PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKdDPR--SHRmllPSGSLfflrIVHGRRSKPD--E 105
Cdd:cd05733     1 PTITEQsPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAK-DPRvsMRR---RSGTL----VIDNHNGGPEdyQ 72

                          90       100
                  ....*....|....*....|.
gi 568997560  106 GSYVCVARNYLGEAVSRNASL 126
Cdd:cd05733    73 GEYQCYASNELGTAISNEIRL 93

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 61.10 E-value: 3.49e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  428 PINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFL--GRDPRATIQ-DQGTLQIKNLRISDTGTYTCVATSSSGETSWS 504
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFpaARERRMHVMpEDDVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                  ....*
gi 568997560  505 AVLDV 509
Cdd:cd05763    86 ATLTV 90

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 61.15 E-value: 3.56e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   35 EHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprSHRMLLPSGSLFFLRIVHGRRSKPDEGSYVCVARN 114
Cdd:cd05874     6 QSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDIDKD---PKVTMKPNTGTLVINIMNGEKAEAYEGVYQCTARN 82


                  ....*....
gi 568997560  115 YLGEAVSRN 123
Cdd:cd05874    83 ERGAAVSNN 91

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 60.33 E-value: 6.77e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGervETDKDDPRSHRM-LLPSGSLFFLRIVhgrrSKPDEGSYVCVARNY 115
Cdd:cd05763     6 PHDITIRAGSTARLECAATGHPTPQIAWQKDG---GTDFPAARERRMhVMPEDDVFFIVDV----KIEDTGVYSCTAQNS 78

                          90
                  ....*....|...
gi 568997560  116 LGeAVSRNASLEV 128
Cdd:cd05763    79 AG-SISANATLTV 90

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 60.33 E-value: 6.82e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  136 RQNPTDVVVAAGEPAILECQPPrGHPEPTIYWKKDKVRIDDKEERISIR--GGKLMISNTRKSDAGMYTCVGTNMVGERD 213
Cdd:cd05730     7 RQSEVNATANLGQSVTLACDAD-GFPEPTMTWTKDGEPIESGEEKYSFNedGSEMTILDVDKLDEAEYTCIAENKAGEQE 85


                  ....*....
gi 568997560  214 SDpAELTVF 222
Cdd:cd05730    86 AE-IHLKVF 93

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 59.83 E-value: 8.59e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  228 LRRPINQVVLEEEAVEFRCQVQGD-PQPTVRWKKDDADLPRGR-----YDIKDDYT-LRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd05750     3 LKEMKSQTVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRpknikIRNKKKNSeLQINKAKLEDSGEYTCVVENILG 82

                          90
                  ....*....|
gi 568997560  301 KVEASATLTV 310
Cdd:cd05750    83 KDTVTGNVTV 92

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 59.80 E-value: 9.32e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  431 QTLAVDG-TALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd05764     9 ELRVLEGqRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEAT 81

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 59.40 E-value: 1.11e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   40 VIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdKDDPRSHrmLLPSGSLFFLRIvhgrrSKPDEGSYVCVARNYLGEA 119
Cdd:cd04969    12 ILAAKGGDVIIECKPKASPKPTISWSKGTELL---TNSSRIC--ILPDGSLKIKNV-----TKSDEGKYTCFAVNFFGKA 81


                  ....*....
gi 568997560  120 VSrNASLEV 128
Cdd:cd04969    82 NS-TGSLSV 89

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 59.29 E-value: 1.37e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  226 TFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRW-KKDDADLPRGRYDI---KDDYTLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd05747     5 TILTKPRSLTVSEGESARFSCDVDGEPAPTVTWmREGQIIVSSQRHQItstEYKSTFEISKVQMSDEGNYTVVVENSEGK 84


                  ....*...
gi 568997560  302 VEASATLT 309
Cdd:cd05747    85 QEAQFTLT 92

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 58.94 E-value: 1.46e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVGERDSDPA 217
Cdd:cd20978     8 EKNVVVKGGQDVTLPCQV-TGVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETL 85

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 59.26 E-value: 1.49e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPPrGHPEPTIYWKKDKVRID--DKEERIS-IRGGKLMISNTRKSDAGMYTCVGTNMVGERDSD 215
Cdd:cd05738     6 PQLKVVEKARTATMLCAAS-GNPDPEISWFKDFLPVDtaTSNGRIKqLRSGALQIENSEESDQGKYECVATNSAGTRYSA 84


                  ....*.
gi 568997560  216 PAELTV 221
Cdd:cd05738    85 PANLYV 90

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 58.75 E-value: 1.86e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLpRGRYDIK-----DDYTLRIKKAMSTDEGTYVCIAENRV 299
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL-QNSPDIQihqegDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 568997560  300 GKVEASATLTV 310
Cdd:cd20972    81 GSDTTSAEIFV 91

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 59.10 E-value: 2.14e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  137 QNPTDVVVAAGEPAILECQpPRGHPEPTIYWKKDKVRI-----DDKEERISIRGGKL----MISNTR-KSDAGMYTCVGT 206
Cdd:cd07693     5 EHPSDLIVSKGDPATLNCK-AEGRPTPTIQWLKNGQPLetdkdDPRSHRIVLPSGSLfflrVVHGRKgRSDEGVYVCVAH 83

                          90
                  ....*....|....*
gi 568997560  207 NMVGERDSDPAELTV 221
Cdd:cd07693    84 NSLGEAVSRNASLEV 98

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 58.69 E-value: 2.35e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  430 NQTLAVDGTALLKCKATGEPLPVISWLK--EGFTFLGRDPRATIQDQG-----TLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd05732    10 NQTAVELEQITLTCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGharvsSLTLKDVQLTDAGRYDCEASNRIGGDQ 89


                  ....*..
gi 568997560  503 WSAVLDV 509
Cdd:cd05732    90 QSMYLEV 96

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 58.23 E-value: 2.69e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  319 QFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfPNQPQQPNSRCSVSPTgDLTITNIQRSDAGYYICQAL 398
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGV-----PIEPAPEDMRRTVDGR-TLIFSNLQPNDTAVYQCNAS 74

                          90
                  ....*....|....
gi 568997560  399 TVAGSILAKAQLEV 412
Cdd:cd04978    75 NVHGYLLANAFLHV 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 58.41 E-value: 2.76e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  424 ILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSG 499
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGD-DLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 58.29 E-value: 2.94e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKddpRSHRMlLPSGSLffLRIVHGRRSkpDEGSYVCVARNYL 116
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFN---TRYIV-RENGTT--LTIRNIRRS--DMGIYLCIASNGV 80

                          90
                  ....*....|..
gi 568997560  117 GEAVSRNASLEV 128
Cdd:cd20970    81 PGSVEKRITLQV 92

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 57.89 E-value: 4.68e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  650 VLTPTTVQVTWTVDRQPQ-FIQGYRVMYRQTSGLQastvWQNLDAKVPTERSAVLVNLKKGVTYEIKVRPYFNEFQGMDS 728
Cdd:cd00063    11 DVTSTSVTLSWTPPEDDGgPITGYVVEYREKGSGD----WKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPS 86


                  ....*..
gi 568997560  729 ESKTVRT 735
Cdd:cd00063    87 ESVTVTT 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 58.06 E-value: 5.08e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  430 NQTLAVDGTALLKCKATGEPLPVISWLK--EGFTFLGRD--PRATIQDQG-----TLQIKNLRISDTGTYTCVATSSSGE 500
Cdd:cd05870    10 NETTVENGAATLSCKAEGEPIPEITWKRasDGHTFSEGDksPDGRIEVKGqhgesSLHIKDVKLSDSGRYDCEAASRIGG 89


                  ....*....
gi 568997560  501 TSWSAVLDV 509
Cdd:cd05870    90 HQKSMYLDI 98

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 57.56 E-value: 5.81e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  441 LKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05856    24 LKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 57.33 E-value: 6.01e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  423 IILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEgftFLGRDP-----RATIQDQGTLQIKNLRISDTGTYTCVATSS 497
Cdd:cd05738     1 IIDMGPQLKVVEKARTATMLCAASGNPDPEISWFKD---FLPVDTatsngRIKQLRSGALQIENSEESDQGKYECVATNS 77


                  ....*...
gi 568997560  498 SGeTSWSA 505
Cdd:cd05738    78 AG-TRYSA 84

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 57.63 E-value: 6.05e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  240 EAVEFRCQVQGDPQPTVRWKKDDADLPRG--RYDIKDDYT-LRIKKAMSTDEGTYVCIAENRVGKVEASATLTVRVR 313
Cdd:cd05730    19 QSVTLACDADGFPEPTMTWTKDGEPIESGeeKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVFAK 95

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 57.16 E-value: 7.52e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  231 PINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPR-GRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATL 308
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHsSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 56.84 E-value: 7.73e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  246 CQVQGDPQPTVRWKKDDADLP-RGRYDIKDDyTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLAsENRIEVEAG-DLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 56.63 E-value: 7.88e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKeeRISIRGGK-LMISNTRKSDAGMYTCVGTNMVGERDSDpA 217
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEV-GGDPVPTVRWRKEDGELPKG--RYEILDDHsLKIRKVTAGDMGSYTCVAENMVGKIEAS-A 79


                  ....
gi 568997560  218 ELTV 221
Cdd:cd05725    80 TLTV 83

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 56.87 E-value: 8.72e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQnllfpnqpQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGS 403
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDL--------IKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGI 77

                          90
                  ....*....|
gi 568997560  404 ILAK-AQLEV 412
Cdd:cd20968    78 AYSKpVTIEV 87

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 56.10 E-value: 1.14e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  238 EEEAVEFRCQVQGDPQPTVRWKKDDADLPRG-RYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 56.48 E-value: 1.33e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKG---EPTTLNCKAEGRPTPTIEWYKDGERVETDKDDprshRMLLPSGSLfflrIVHGRRSKPDEGS 107
Cdd:cd04967     2 PVFEEQPDDTIFPEDsdeKKVALNCRARANPVPSYRWLMNGTEIDLESDY----RYSLVDGTL----VISNPSKAKDAGH 73

                          90       100
                  ....*....|....*....|..
gi 568997560  108 YVCVARNYLGEAVSRNASLEVA 129
Cdd:cd04967    74 YQCLATNTVGSVLSREATLQFG 95

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 56.33 E-value: 1.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRI--DDKEERISIRGGKLMISN-----TRKSDAGMYTCVGTN 207
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSA-ESDPPPKIEWKKDGVLLnlVSDERRQQLPNGSLLITSvvhskHNKPDEGFYQCVAQN 82

                          90
                  ....*....|....*
gi 568997560  208 -MVGERDSDPAELTV 221
Cdd:cd05722    83 eSLGSIVSRTARVTV 97

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 56.27 E-value: 1.82e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllFPNQPQQPNSRCSVSPTGDLTITNIQR---SDAGYYI 394
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNG-----VPIDPSSIPGKYKIESEYGVHVLHIRRvtvEDSAVYS 75

                          90
                  ....*....|....*...
gi 568997560  395 CQALTVAGSILAKAQLEV 412
Cdd:cd20951    76 AVAKNIHGEASSSASVVV 93

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 55.96 E-value: 2.20e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKddprSHRMLLPSGSLFFLRIVHgrRSKPDEGSYVC 110
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDS----AHKMLVRENGRHSLIIEP--VTKRDAGIYTC 74

                          90
                  ....*....|....*...
gi 568997560  111 VARNYLGEaVSRNASLEV 128
Cdd:cd05744    75 IARNRAGE-NSFNAELVV 91

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 55.49 E-value: 2.54e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   38 SDVIVSKGEPTTLNCKAEGRPTPTIEWYK-DGErvetdkddprshrmlLPSGSLFF------LRIVhgRRSKPDEGSYVC 110
Cdd:cd05731     3 SSTMVLRGGVLLLECIAEGLPTPDIRWIKlGGE---------------LPKGRTKFenfnktLKIE--NVSEADSGEYQC 65


                  ....*....
gi 568997560  111 VARNYLGEA 119
Cdd:cd05731    66 TASNTMGSA 74

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 55.27 E-value: 2.95e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  229 RRPI-NQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYdIKDDY------TLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd20973     1 IQTLrDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRR-FQIDQdedglcSLIISDVCGDDSGKYTCKAVNSLGE 79


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd20973    80 ATCSAELTV 88

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.48 E-value: 3.00e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHP-SDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkdDPRSHRMLLPSGSLFFLRIVhgrrsKPDEGSYV 109
Cdd:cd20978     1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPL-----QGPMERATVEDGTLTIINVQ-----PEDTGYYG 70

                          90
                  ....*....|....*....
gi 568997560  110 CVARNYLGEaVSRNASLEV 128
Cdd:cd20978    71 CVATNEIGD-IYTETLLHV 88

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 55.30 E-value: 3.12e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  134 DFRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDdKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVGERD 213
Cdd:cd05728     1 EWLKVISDTEADIGSSLRWECKA-SGNPRPAYRWLKNGQPLA-SENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIY 78


                  ....*...
gi 568997560  214 SDpAELTV 221
Cdd:cd05728    79 AS-AELAV 85

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 55.35 E-value: 3.38e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  158 RGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKS-DAGMYTCVGTNMVGERDSDPAELT 220
Cdd:cd05849    29 RANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNPDKYkDAGRYVCIVSNIYGKVRSREATLS 92

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 54.50 E-value: 3.94e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  441 LKCKATGEPLPVISWLKEGFTfLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVL 507
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQ-VTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 54.94 E-value: 4.12e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   32 RIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDkddprSHRMLLPSGSLFFLRIvhgrrSKPDEGSYVCV 111
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKEN-----NRIAVLESGSLRIHNV-----QKEDAGQYRCV 70

                          90
                  ....*....|....*..
gi 568997560  112 ARNYLGEAVSRNASLEV 128
Cdd:cd20968    71 AKNSLGIAYSKPVTIEV 87

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 55.19 E-value: 4.22e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKD--KVRIDDKEERISIRGGK--LMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd05744     3 FLQAPGDLEVQEGRLCRFDCKV-SGLPTPDLFWQLNgkPVRPDSAHKMLVRENGRhsLIIEPVTKRDAGIYTCIARNRAG 81

                          90
                  ....*....|.
gi 568997560  211 ERDSDpAELTV 221
Cdd:cd05744    82 ENSFN-AELVV 91

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.90 E-value: 4.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDQG---TLQIKNLRISDTGTYTCVATSS 497
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEG-KELQNSPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNS 79


                  ....*...
gi 568997560  498 SGETSWSA 505
Cdd:cd20972    80 VGSDTTSA 87

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 54.88 E-value: 4.88e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   45 GEPTTLNCKAEGRPTPTIEWYKDGERVetdkddPRSHR-MLLPSGSLfflrIVHGRRSKPDEGSYVCVARNYLGEAVSRN 123
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDGRRL------PLNHRqRVFPNGTL----VIENVQRSSDEGEYTCTARNQQGQSASRS 84


                  ....*
gi 568997560  124 ASLEV 128
Cdd:cd20958    85 VFVKV 89

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 54.53 E-value: 4.89e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  319 QFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCSVSpTGDLTITNIQRSDAGYYICQAL 398
Cdd:cd05728     1 EWLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNG--------QPLASENRIEVE-AGDLRITKLSLSDSGMYQCVAE 71

                          90
                  ....*....|....
gi 568997560  399 TVAGSILAKAQLEV 412
Cdd:cd05728    72 NKHGTIYASAELAV 85

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 54.11 E-value: 5.39e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  242 VEFRCQVQGDPQPTVRWKKDDADLPR-GRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLT 309
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTEsGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 54.58 E-value: 6.43e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEA---VEFRCQVQGDPQPTVRWKKD--DADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRV 299
Cdd:cd05849     2 PVFEEQPIDTIYPEESTegkVSVNCRARANPFPIYKWRKNnlDIDLTNDRYSMVGGNLVINNPDKYKDAGRYVCIVSNIY 81

                          90
                  ....*....|.
gi 568997560  300 GKVEAS-ATLT 309
Cdd:cd05849    82 GKVRSReATLS 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 54.47 E-value: 6.57e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  242 VEFRCQVQGDPQPTVRWKKDDADLPR----GRYDIKD-DYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05857    22 VKFRCPAAGNPTPTMRWLKNGKEFKQehriGGYKVRNqHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 54.26 E-value: 7.57e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  226 TFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIK----DDYTLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSkyriLADGLLINKVTQDDTGEYTCRAYQVNSI 80


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd20949    81 ASDMQERTV 89

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 54.18 E-value: 7.68e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDY---TLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAgvgELHIQDVLPEDHGTYTCLAKNAAGQ 81


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd20976    82 VSCSAWVTV 90

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 54.40 E-value: 7.77e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEgsqnllfpNQPQQPNSRCSVSPTGD----LTITNIQRSDAGYY 393
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRN--------RQPVRPDQRRFAEEAEGglcrLRILAAERGDAGFY 72

                          90
                  ....*....|....*....
gi 568997560  394 ICQALTVAGSILAKAQLEV 412
Cdd:cd20975    73 TCKAVNEYGARQCEARLEV 91

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 54.05 E-value: 8.25e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  143 VVAAGEPAILECQPPRGHPEPTIYWKKDKVRID-DKEERISIRGGK----LMISNTRKSDAGMYTCVGTNMVGeRDSDPA 217
Cdd:cd05750    10 TVQEGSKLVLKCEATSENPSPRYRWFKDGKELNrKRPKNIKIRNKKknseLQINKAKLEDSGEYTCVVENILG-KDTVTG 88


                  ....
gi 568997560  218 ELTV 221
Cdd:cd05750    89 NVTV 92

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 54.48 E-value: 8.33e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKD------DADLPRGRYDIKDD---YTLRI--KKAMSTDEGTYVC 293
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNgqpletDKDDPRSHRIVLPSgslFFLRVvhGRKGRSDEGVYVC 80

                          90
                  ....*....|....*...
gi 568997560  294 IAENRVGK-VEASATLTV 310
Cdd:cd07693    81 VAHNSLGEaVSRNASLEV 98

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 53.76 E-value: 8.64e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  235 VVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKD-DYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05876     6 VALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNhNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 53.94 E-value: 8.79e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDgervetDKDDPRSHRMLLPSGSLFFLRIVHGrrskpDEGSYVCVARNYL 116
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKE------DGELPKGRYEILDDHSLKIRKVTAG-----DMGSYTCVAENMV 72

                          90
                  ....*....|..
gi 568997560  117 GEAVSRnASLEV 128
Cdd:cd05725    73 GKIEAS-ATLTV 83

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 54.25 E-value: 9.41e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKGNPQPAVFWQKEgsqnlLFPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGS 403
Cdd:cd05738     6 PQLKVVEKARTATMLCAASGNPDPEISWFKD-----FLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGT 80

                          90
                  ....*....|
gi 568997560  404 -ILAKAQLEV 412
Cdd:cd05738    81 rYSAPANLYV 90

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 54.24 E-value: 9.55e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  139 PTDVVVAAGEPAILECQpPRGHPEPTIYWKKDKVRIDD------KEERISI-RGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd20954     8 PVDANVAAGQDVMLHCQ-ADGFPTPTVTWKKATGSTPGeykdllYDPNVRIlPNGTLVFGHVQKENEGHYLCEAKNGIG 85

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 53.79 E-value: 1.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVGERDSDPAE 218
Cdd:cd20968     6 PTNVTIIEGLKAVLPCTT-MGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVT 84


                  ...
gi 568997560  219 LTV 221
Cdd:cd20968    85 IEV 87

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 53.93 E-value: 1.14e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVI-VSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRsHRMlLPSGSLFFLRIVhgrrsKPDEGSY 108
Cdd:cd20969     1 RAAIRDRKAQQVfVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGR-LTV-FPDGTLEVRYAQ-----VQDNGTY 73

                          90       100
                  ....*....|....*....|
gi 568997560  109 VCVARNYLGEAvSRNASLEV 128
Cdd:cd20969    74 LCIAANAGGND-SMPAHLHV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 53.61 E-value: 1.14e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   32 RIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVEtdkDDPRSHRMLLPSGSLFFLRIVHGrrskpDEGSYVCV 111
Cdd:cd04978     1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIE---PAPEDMRRTVDGRTLIFSNLQPN-----DTAVYQCN 72

                          90
                  ....*....|....*..
gi 568997560  112 ARNYLGEAVSrNASLEV 128
Cdd:cd04978    73 ASNVHGYLLA-NAFLHV 88

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 53.93 E-value: 1.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDG--TALLKCKATGEPLPVISWLKEGFTFLGRDP--RATIQDQGTLQIKNLRISDTGTYTCVATSS 497
Cdd:cd20969     1 RAAIRDRKAQQVFVDEghTVQFVCRADGDPPPAILWLSPRKHLVSAKSngRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                          90
                  ....*....|..
gi 568997560  498 SGETSWSAVLDV 509
Cdd:cd20969    81 GGNDSMPAHLHV 92

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 53.74 E-value: 1.35e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQnllFPNQPQqpnsrCSVSPTGD---LTITNIQRSDAGYY 393
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKE---LQNSPD-----IQIHQEGDlhsLIIAEAFEEDTGRY 72

                          90
                  ....*....|....*....
gi 568997560  394 ICQALTVAGSILAKAQLEV 412
Cdd:cd20972    73 SCLATNSVGSDTTSAEIFV 91

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 58.10 E-value: 1.53e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  258 WKKDDADLPRgRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTVRVRPVAPPQFVVRPrdQIVAQGRTVTF 337
Cdd:PHA02785   65 WEKRGADNDR-IIPIDNGSNMLILNPTQSDSGIYICITKNETYCDMMSLNLTIVSVSESNIDLISYP--QIVNERSTGEM 141

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  338 PCetkgnPQPAVFWQKEGSQNLLFPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICqaltVAGSILAKAQLEVTDVLT 417
Cdd:PHA02785  142 VC-----PNINAFIASNVNADIIWSGHRRLRNKRLKQRTPGIITIEDVRKNDAGYYTC----VLKYIYGDKTYNVTRIVK 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  418 ----DRPPPIILQGPINQTLAVDGTALLKCKATGEPlPVIS----WLKEGFTFL-------GR----------DPRATIQ 472
Cdd:PHA02785  213 levrDRIIPPTMQLPEGVVTSIGSNLTIACRVSLRP-PTTDadvfWISNGMYYEeddedgdGRisvankiyttDKRRVIT 291

                         250       260
                  ....*....|....*....|..
gi 568997560  473 DQgtLQIKNLRISDTGTYTCVA 494
Cdd:PHA02785  292 SR--LNINPVKEEDATTFTCMA 311

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 53.22 E-value: 1.74e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  228 LRRPINQVVLEEEAVEFRCQVQGDPQPTVRW---KKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEA 304
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWrlnGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLA 82


                  ....*..
gi 568997560  305 SATLTVR 311
Cdd:cd04978    83 NAFLHVL 89

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 53.40 E-value: 1.78e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560   45 GEPTTLNCKAEGRPTPTIEWYKDGERVEtdkDDPRSHRMLLPSGSLFFLRIvhgrrSKPDEGSYVCVARNYLGEA 119
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIE---SGEEKYSFNEDGSEMTILDV-----DKLDEAEYTCIAENKAGEQ 84

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 53.16 E-value: 1.91e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEA--VEFRCQVQGDPQPTVRW----KKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENR 298
Cdd:cd20969     1 RAAIRDRKAQQVFVDEGhtVQFVCRADGDPPPAILWlsprKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANA 80

                          90
                  ....*....|..
gi 568997560  299 VGKVEASATLTV 310
Cdd:cd20969    81 GGNDSMPAHLHV 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 52.99 E-value: 2.18e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  222 FERPTFLRRPInQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRGRYDI----KDDYTLRIKKAMSTDEGTYVCIAE 296
Cdd:cd05729     3 FTDTEKMEERE-HALPAANKVRLECGAGGNPMPNITWLKDGKEFkKEHRIGGtkveEKGWSLIIERAIPRDKGKYTCIVE 81

                          90
                  ....*....|....
gi 568997560  297 NRVGKVEASATLTV 310
Cdd:cd05729    82 NEYGSINHTYDVDV 95

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 53.01 E-value: 2.19e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  420 PPPI-ILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGT-LQIKNLRISDTGTYTCVATSS 497
Cdd:cd05730     1 PPTIrARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENK 80

                          90
                  ....*....|..
gi 568997560  498 SGETSWSAVLDV 509
Cdd:cd05730    81 AGEQEAEIHLKV 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 52.79 E-value: 2.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  322 VRPRDQIVAQGRTVTFPCET-KGNPQPAVFWQKEGSQ-NLLfpnqpqqpNSRCSVSPTGDLTITNIQRSDAGYYICQALT 399
Cdd:cd05724     2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPlNLD--------NERVRIVDDGNLLIAEARKSDEGTYKCVATN 73


                  ...
gi 568997560  400 VAG 402
Cdd:cd05724    74 MVG 76

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 52.80 E-value: 2.85e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKddprSHRMLLPSGSLFFLrIVHGRRSKpDEGSYVC 110
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDS----AHKMLVRENGVHSL-IIEPVTSR-DAGIYTC 74


                  ....*...
gi 568997560  111 VARNYLGE 118
Cdd:cd20990    75 IATNRAGQ 82

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 52.69 E-value: 2.88e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEA--VEFRCQVQGDPQPTVRWKKDDADLPRG-RYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd05852     1 PTFEFNPMKKKILAAKGgrVIIECKPKAAPKPKFSWSKGTELLVNNsRISIWDDGSLEILNITKLDEGSYTCFAENNRGK 80


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd05852    81 ANSTGVLSV 89

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 52.71 E-value: 2.92e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   28 DFPPRIVehpsdvIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRmlLPSGSLFFlrivhGRRSKPDEGS 107
Cdd:cd05738     3 DMGPQLK------VVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQ--LRSGALQI-----ENSEESDQGK 69

                          90       100
                  ....*....|....*....|.
gi 568997560  108 YVCVARNYLGEAVSRNASLEV 128
Cdd:cd05738    70 YECVATNSAGTRYSAPANLYV 90

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 52.53 E-value: 3.01e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  428 PINQTLAVDGTALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVA 494
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG-KPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFV 73

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 3.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTlAVDGTAL-LKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQ-GTLQIKNLRISDTGTYTCVATSSS 498
Cdd:cd20976     1 APSFSSVPKDLE-AVEGQDFvAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 568997560  499 GETSWSAVLDV 509
Cdd:cd20976    80 GQVSCSAWVTV 90

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 52.22 E-value: 3.29e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  425 LQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDqGTLQIKNLRISDTGTYTCVATSSSGETSWS 504
Cdd:cd05728     3 LKVISDTEADIGSSLRWECKASGNPRPAYRWLKNG-QPLASENRIEVEA-GDLRITKLSLSDSGMYQCVAENKHGTIYAS 80


                  ....*
gi 568997560  505 AVLDV 509
Cdd:cd05728    81 AELAV 85

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 52.31 E-value: 4.25e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  434 AVDGTALLKCKATGEPLPVISWLKeGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05852    15 AKGGRVIIECKPKAAPKPKFSWSK-GTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 52.29 E-value: 4.72e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHP-SDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKdDPRShRMLLPSGSLfFLRIVHGRRSKPDEGSYV 109
Cdd:cd05875     1 PTITKQSaKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKFFNVAK-DPRV-SMRRRSGTL-VIDFRGGGRPEDYEGEYQ 77

                          90
                  ....*....|....*...
gi 568997560  110 CVARNYLGEAVSRNASLE 127
Cdd:cd05875    78 CFARNKFGTALSNKIRLQ 95

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 51.85 E-value: 4.99e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  226 TFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDA-DLPRGR----YDIKDDYTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGtDFPAARerrmHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                          90
                  ....*....|
gi 568997560  301 KVEASATLTV 310
Cdd:cd05763    81 SISANATLTV 90

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 51.69 E-value: 5.56e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLprgRYDI------KDDY---TLRIKKAMSTDEGTYVCIA 295
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEML---QYNTdrislyQDNCgriCLLIQNANKKDAGWYTVSA 77

                          90
                  ....*....|....*
gi 568997560  296 ENRVGKVEASATLTV 310
Cdd:cd05892    78 VNEAGVVSCNARLDV 92

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 51.65 E-value: 6.08e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGF--TFLGRDPRATIQDQG---TLQIKNLRISDTGTYTCVATS 496
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVpiDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 568997560  497 SSGETSWSAVLDV 509
Cdd:cd20951    81 IHGEASSSASVVV 93

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 51.43 E-value: 6.09e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   231 PINQVVLEEEAVEFRCQV-QGDPQPTVRWKKDDADLPRGRYDIKDDY-----TLRIKKAMSTDEGTYVCIAENRVGKVEA 304
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNNPGGSATL 82


                   ....
gi 568997560   305 SATL 308
Cdd:pfam00047   83 STSL 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 51.24 E-value: 6.15e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprshrmllpsgslFFLRIVhgrrSKPDEGSYVCVARNYL 116
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN--------------FFTLSV----SAEDSGTYTCVARNGR 67

                           90
                   ....*....|..
gi 568997560   117 GEAVSRNASLEV 128
Cdd:pfam13895   68 GGKVSNPVELTV 79

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 51.59 E-value: 6.26e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLG--RDPRATIQDQGTLQIKNLRISDTGTYTCVATSSS 498
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSsqRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSE 82


                  ..
gi 568997560  499 GE 500
Cdd:cd05747    83 GK 84

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 51.47 E-value: 6.69e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKvRID---DKEERISIR--GGKLMISNTRKSDAGMYTCVGTNMV 209
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAA-TGHPTPQIAWQKDG-GTDfpaARERRMHVMpeDDVFFIVDVKIEDTGVYSCTAQNSA 79

                          90
                  ....*....|..
gi 568997560  210 GERDSDpAELTV 221
Cdd:cd05763    80 GSISAN-ATLTV 90

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 51.38 E-value: 7.46e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQ 396
Cdd:cd20957     1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG--------KPLGHSSRVQILSEDVLVIPSVKREDKGMYQCF 72

                          90
                  ....*....|....*.
gi 568997560  397 ALTVAGSILAKAQLEV 412
Cdd:cd20957    73 VRNDGDSAQATAELKL 88

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 51.38 E-value: 8.72e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkddPRSHRMLLPSGSlfflRIVHGRRSKPDEGSYVCVARN 114
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPL------GHSSRVQILSED----VLVIPSVKREDKGMYQCFVRN 75

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 51.34 E-value: 9.49e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEG--FTFLGRDPRatIQDQG---TLQIKNLRISDTGTYTCVATS 496
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGkpVRPDSAHKM--LVRENgrhSLIIEPVTKRDAGIYTCIARN 78

                          90
                  ....*....|...
gi 568997560  497 SSGETSWSAVLDV 509
Cdd:cd05744    79 RAGENSFNAELVV 91

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 51.27 E-value: 9.81e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRshrmlLPSGSLFFLRIVHGRRSKP-DEGSYV 109
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGK-----YKIESEYGVHVLHIRRVTVeDSAVYS 75

                          90
                  ....*....|....*....
gi 568997560  110 CVARNYLGEAVSrNASLEV 128
Cdd:cd20951    76 AVAKNIHGEASS-SASVVV 93

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 50.92 E-value: 1.40e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIRGGK-----LMISNTRKSDAGMYTCVGTNMV 209
Cdd:cd05892     3 FIQKPQNKKVLEGDPVRLECQI-SAIPPPQIFWKKNNEMLQYNTDRISLYQDNcgricLLIQNANKKDAGWYTVSAVNEA 81


                  .
gi 568997560  210 G 210
Cdd:cd05892    82 G 82

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 50.55 E-value: 1.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWykdgeRVETDKDDPRSHRMLL-PSGSLFFLRIvhgrrSKPDEGSYV 109
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHW-----ISPEGKLISNSSRTLVyDNGTLDILIT-----TVKDTGAFT 70

                          90
                  ....*....|...
gi 568997560  110 CVARNYLGEAVSR 122
Cdd:cd05764    71 CIASNPAGEATAR 83

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 50.29 E-value: 1.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   34 VEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkddPRSHRMLLPSGSLFFLRIvhgrrSKPDEGSYVCVAR 113
Cdd:cd05728     3 LKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPL------ASENRIEVEAGDLRITKL-----SLSDSGMYQCVAE 71

                          90
                  ....*....|....*
gi 568997560  114 NYLGeAVSRNASLEV 128
Cdd:cd05728    72 NKHG-TIYASAELAV 85

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 50.71 E-value: 1.52e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprshRMLLPSGslffLRIVHGRRSKP-DEGSY 108
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAD-----RSTCEAG----VGELHIQDVLPeDHGTY 71

                          90
                  ....*....|.
gi 568997560  109 VCVARNYLGEA 119
Cdd:cd20976    72 TCLAKNAAGQV 82

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 50.60 E-value: 1.57e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  226 TFLRrpiNQVVLEEEAVEFRCQVQGDPQPTVRWKK------DDADLPRGRYDIKDDY---TLRIKKAMSTDEGTYVCIAE 296
Cdd:cd05732     6 TYLE---NQTAVELEQITLTCEAEGDPIPEITWRRatrgisFEEGDLDGRIVVRGHArvsSLTLKDVQLTDAGRYDCEAS 82

                          90
                  ....*....|....
gi 568997560  297 NRVGKVEASATLTV 310
Cdd:cd05732    83 NRIGGDQQSMYLEV 96

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 50.24 E-value: 1.64e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  242 VEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd04968    19 VTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 50.70 E-value: 1.65e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAG---EPAILECQPpRGHPEPTIYWKKDKVRID-DKEERISIRGGKLMISNTRKS-DAGMYTCVGTNMV 209
Cdd:cd04967     4 FEEQPDDTIFPEDsdeKKVALNCRA-RANPVPSYRWLMNGTEIDlESDYRYSLVDGTLVISNPSKAkDAGHYQCLATNTV 82

                          90
                  ....*....|
gi 568997560  210 GERDSDPAEL 219
Cdd:cd04967    83 GSVLSREATL 92

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 50.63 E-value: 1.71e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQnllFPNQPQQPNSRCSVSPTGDLTITNI-----QRSDAGY 392
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQP---LETDKDDPRSHRIVLPSGSLFFLRVvhgrkGRSDEGV 77

                          90       100
                  ....*....|....*....|...
gi 568997560  393 YICQA---LTVAGSilAKAQLEV 412
Cdd:cd07693    78 YVCVAhnsLGEAVS--RNASLEV 98

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 50.54 E-value: 1.83e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEgsqnllfpNQPQQPN-SRCSVSPTGD----LTITNIQRSDAGY 392
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKN--------NEMLQYNtDRISLYQDNCgricLLIQNANKKDAGW 72

                          90       100
                  ....*....|....*....|
gi 568997560  393 YICQALTVAGSILAKAQLEV 412
Cdd:cd05892    73 YTVSAVNEAGVVSCNARLDV 92

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 50.27 E-value: 1.89e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   426 QGPINQTLAVDGTALLKCKA-TGEPLPVISWLKEGFTFLGRDPRATIQD---QGTLQIKNLRISDTGTYTCVATSSSGET 501
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGrttQSSLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....*.
gi 568997560   502 SWSAVL 507
Cdd:pfam00047   81 TLSTSL 86

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409363 Cd Length: 102 Bit Score: 50.50 E-value: 2.02e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQG-PINQTLAVDGTALLKCKATGEPLPVISWLK--------EGF------TFLGRDPRATIQDQGTLQIKNLRISD 486
Cdd:cd04974     1 PILQAGlPANQTVVLGSDVEFHCKVYSDAQPHIQWLKhvevngskYGPdglpyvTVLKVAGVNTTGEENTLTISNVTFDD 80

                          90
                  ....*....|...
gi 568997560  487 TGTYTCVATSSSG 499
Cdd:cd04974    81 AGEYICLAGNSIG 93

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 50.31 E-value: 2.18e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   29 FPPRIVEHPSDVIVSKGEP---TTLNCKAEGRPTPTIEWYKDGERVetdKDDPRSHRMLLpSGSLFFLRIVHGRrskpDE 105
Cdd:cd05850     1 YGPVFEEQPSSTLFPEGSAeekVTLACRARASPPATYRWKMNGTEL---KMEPDSRYRLV-AGNLVISNPVKAK----DA 72

                          90       100
                  ....*....|....*....|.
gi 568997560  106 GSYVCVARNYLGEAVSRNASL 126
Cdd:cd05850    73 GSYQCLASNRRGTVVSREASL 93

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 50.30 E-value: 2.24e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  433 LAVDGTALLKCKATGEPLPVISWLKEGFTFL--GRDPRATIQDQG-TLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05729    16 LPAANKVRLECGAGGNPMPNITWLKDGKEFKkeHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 49.93 E-value: 2.83e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLE---EEAVEFRCQVQGDPQPTVRWKKDDADL---PRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENR 298
Cdd:cd04967     2 PVFEEQPDDTIFPEdsdEKKVALNCRARANPVPSYRWLMNGTEIdleSDYRYSLVDGTLVISNPSKAKDAGHYQCLATNT 81

                          90
                  ....*....|.
gi 568997560  299 VGKVEAS-ATL 308
Cdd:cd04967    82 VGSVLSReATL 92

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 49.51 E-value: 3.25e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  323 RPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfPNQPQQPNSRCSVSpTGDLTITNIQRSDAGYYICQALTVAG 402
Cdd:cd05867     5 RPQSHLYGPGETARLDCQVEGIPTPNITWSINGA-----PIEGTDPDPRRHVS-SGALILTDVQPSDTAVYQCEARNRHG 78

                          90
                  ....*....|
gi 568997560  403 SILAKAQLEV 412
Cdd:cd05867    79 NLLANAHVHV 88

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 49.94 E-value: 3.26e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAG---EPAILECQPpRGHPEPTIYWKKDKVRID-DKEERISIRGGKLMISNTRKS-DAGMYTCVGTNMV 209
Cdd:cd05848     4 FVQEPDDAIFPTDsdeKKVILNCEA-RGNPVPTYRWLRNGTEIDtESDYRYSLIDGNLIISNPSEVkDSGRYQCLATNSI 82


                  .
gi 568997560  210 G 210
Cdd:cd05848    83 G 83

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.81 E-value: 3.30e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  426 QGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQGT-LQIKNLRISDTGTYTCVATS-SSGETSW 503
Cdd:cd20970     7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgVPGSVEK 86


                  ....*.
gi 568997560  504 SAVLDV 509
Cdd:cd20970    87 RITLQV 92

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 49.40 E-value: 3.63e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL--PRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGkv 302
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLisNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAG-- 78

                          90
                  ....*....|
gi 568997560  303 EASATLTVRV 312
Cdd:cd05764    79 EATARVELHI 88

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 49.49 E-value: 3.79e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPqfVVRPRDQIVA-QGRTVTFPCETKGNPQPAVFWQKEGSQnllFPNqpqqpNSRCSVSPTGDLTITNIQR-SDAGYYI 394
Cdd:cd20958     1 PP--FIRPMGNLTAvAGQTLRLHCPVAGYPISSITWEKDGRR---LPL-----NHRQRVFPNGTLVIENVQRsSDEGEYT 70


                  ...
gi 568997560  395 CQA 397
Cdd:cd20958    71 CTA 73

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 49.55 E-value: 3.93e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  229 RRPINQVVLEEEAVEFRCQVQGDPQPTVRW-KKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd20968     4 RPPTNVTIIEGLKAVLPCTTMGNPKPSVSWiKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 49.78 E-value: 3.99e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  227 FLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRG---RYDIKDDYTLRIK-----KAMSTDEGTYVCIAEN 297
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVsdeRRQQLPNGSLLITsvvhsKHNKPDEGFYQCVAQN 82

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 49.56 E-value: 4.08e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfpnQPQQPNSRCSVSP-TGDLTITNIQRSDAGYYIC 395
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQ-------PLQYAADRSTCEAgVGELHIQDVLPEDHGTYTC 73

                          90
                  ....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEV 412
Cdd:cd20976    74 LAKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 49.41 E-value: 4.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEW-YKDGERVETDKDD-PRSHRM-LLPSGSLFFLRIVhgrrsKPDEG 106
Cdd:cd05734     1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkHSKGSGVPQFQHIvPLNGRIqLLSNGSLLIKHVL-----EEDSG 75

                          90       100
                  ....*....|....*....|..
gi 568997560  107 SYVCVARNYLGEAVSRNASLEV 128
Cdd:cd05734    76 YYLCKVSNDVGADISKSMYLTV 97

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 49.47 E-value: 4.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  222 FERPTFLR-----RPINQvvleeeAVEFRCQVQGDPQPTVRWKKDDADLPR---GRyDIKDDYTLRIKKAMSTDEGTYVC 293
Cdd:cd05856     3 FTQPAKMRrrviaRPVGS------SVRLKCVASGNPRPDITWLKDNKPLTPpeiGE-NKKKKWTLSLKNLKPEDSGKYTC 75

                          90
                  ....*....|....*..
gi 568997560  294 IAENRVGKVEASATLTV 310
Cdd:cd05856    76 HVSNRAGEINATYKVDV 92

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 49.48 E-value: 4.70e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPR-GRYDIKDDYT--------LRIKKAMSTDEGTYVCIA 295
Cdd:cd20956     2 PVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPEsPRFRVGDYVTsdgdvvsyVNISSVRVEDGGEYTCTA 81

                          90
                  ....*....|....*
gi 568997560  296 ENRVGKVEASATLTV 310
Cdd:cd20956    82 TNDVGSVSHSARINV 96

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 49.23 E-value: 4.90e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  246 CQVQGDPQPTVRWKKDDADLPrGRY-DIKDDY--------TLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd20954    23 CQADGFPTPTVTWKKATGSTP-GEYkDLLYDPnvrilpngTLVFGHVQKENEGHYLCEAKNGIG 85

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 49.08 E-value: 5.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  138 NPTDVVVAAGEPAILECQPPrGHPEPTIYWKKdkvRIDDKEERI----SIRG-------GKLMISNTRKSDAGMYTCVGT 206
Cdd:cd05765     6 SPTHQTVKVGETASFHCDVT-GRPQPEITWEK---QVPGKENLImrpnHVRGnvvvtniGQLVIYNAQPQDAGLYTCTAR 81


                  ....
gi 568997560  207 NMVG 210
Cdd:cd05765    82 NSGG 85

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 49.57 E-value: 5.10e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQG-PINQTLAVDGTALLKCKATGEPLPVISWLK-----------EGFTFLGRDPRA----TIQDQGTLQIKNLRIS 485
Cdd:cd05858     1 PILQAGlPANTSVVVGTDAEFVCKVYSDAQPHIQWLKhvekngskygpDGLPYVEVLKTAgvntTDKEIEVLYLRNVTFE 80

                          90       100
                  ....*....|....*....|....*
gi 568997560  486 DTGTYTCVATSSSG---ETSWSAVL 507
Cdd:cd05858    81 DAGEYTCLAGNSIGishHSAWLTVL 105

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 48.86 E-value: 5.32e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEgsqnllfpNQPQQPNSRCSVSpTGDLTITNIQRSDAGYYICQ 396
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKI--------LEPMPATAEISMS-GAVLKIFNIQPEDEGTYECE 71

                          90
                  ....*....|....*.
gi 568997560  397 ALTVAGSILAKAQLEV 412
Cdd:cd05851    72 AENIKGKDKHQARVYV 87

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 48.98 E-value: 5.34e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  138 NPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDD--KEERISIRGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd04978     5 EPPSLVLSPGETGELICEA-EGNPQPTITWRLNGVPIEPapEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 48.72 E-value: 5.63e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   39 DVIVSKGEPTTLNCKAEGRPTPTIEWYKDGE------RVETDKDDPRSHRMLL--PSGSlfflrivhgrrskpDEGSYVC 110
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDDNpivesrRFQIDQDEDGLCSLIIsdVCGD--------------DSGKYTC 71


                  ....*....
gi 568997560  111 VARNYLGEA 119
Cdd:cd20973    72 KAVNSLGEA 80

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 48.87 E-value: 6.01e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsQNLlfpNQPQQPNSRCSVSPTGdLTITNIQRSDAGYYICQALT 399
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNG-QPI---SASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQ 76


                  ...
gi 568997560  400 VAG 402
Cdd:cd20949    77 VNS 79

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 48.73 E-value: 6.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprshRMLLPSGSLFFLRIVHGrrSKPDEGSYV 109
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPD-----IQIHQEGDLHSLIIAEA--FEEDTGRYS 73

                          90
                  ....*....|..
gi 568997560  110 CVARNYLGEAVS 121
Cdd:cd20972    74 CLATNSVGSDTT 85

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 49.64 E-value: 6.24e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKG-NPQPAVFW--QKEG-------SQNLLFPNQPQQPNSRCSVSPTGD----LTITNIQRSD 389
Cdd:cd00099     5 PRSLSVQEGESVTLSCEVSSsFSSTYIYWyrQKPGqgpefliYLSSSKGKTKGGVPGRFSGSRDGTssfsLTISNLQPED 84


                  ....*...
gi 568997560  390 AGYYICQA 397
Cdd:cd00099    85 SGTYYCAV 92

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 48.79 E-value: 7.12e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIRG--GKLMISNTRKSDAGMYTCVGTNMVGERDSDp 216
Cdd:cd20976     8 PKDLEAVEGQDFVAQCSA-RGKPVPRITWIRNAQPLQYAADRSTCEAgvGELHIQDVLPEDHGTYTCLAKNAAGQVSCS- 85


                  ....*
gi 568997560  217 AELTV 221
Cdd:cd20976    86 AWVTV 90

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 48.31 E-value: 8.91e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQK-EGSqnllfpnqpqQPNSRCSVSPTGDLTITNIQRSDAGYYIC 395
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKvDGS----------PSSQWEITTSEPVLEIPNVQFEDEGTYEC 70

                          90
                  ....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEV 412
Cdd:cd04968    71 EAENSRGKDTVQGRIIV 87

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 48.17 E-value: 9.49e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  430 NQTLAVDGTALLKCKATGEPLPVISWLKEGftflGRDP--RATIQD-QGTLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd05731     4 STMVLRGGVLLLECIAEGLPTPDIRWIKLG----GELPkgRTKFENfNKTLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 48.24 E-value: 1.01e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  137 QNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEER-ISIRGGKLMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd05764     5 RHTHELRVLEGQRATLRCKA-RGDPEPAIHWISPEGKLISNSSRtLVYDNGTLDILITTVKDTGAFTCIASNPAGE 79

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 47.98 E-value: 1.03e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   38 SDVIVSKGEPTTLNCKAEGRPTPTIEWykdgervetdkddprshrmLLPSGSLFFLRIVHGRRSK---------PDEGSY 108
Cdd:cd05876     3 SSLVALRGQSLVLECIAEGLPTPTVKW-------------------LRPSGPLPPDRVKYQNHNKtlqllnvgeSDDGEY 63

                          90
                  ....*....|.
gi 568997560  109 VCVARNYLGEA 119
Cdd:cd05876    64 VCLAENSLGSA 74

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 48.35 E-value: 1.03e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRID--DKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd05867     6 PQSHLYGPGETARLDCQV-EGIPTPNITWSINGAPIEgtDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 48.32 E-value: 1.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGR--DPRA--TIQDQGTLQIknLRI-------SDTGTY 490
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDkdDPRShrIVLPSGSLFF--LRVvhgrkgrSDEGVY 78

                          90       100
                  ....*....|....*....|
gi 568997560  491 TCVATSSSGE-TSWSAVLDV 509
Cdd:cd07693    79 VCVAHNSLGEaVSRNASLEV 98

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 47.95 E-value: 1.20e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRG-RYDIKDDYTLRIKKA-MSTDEGTYVCIAENRVGkV 302
Cdd:cd20958     1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNhRQRVFPNGTLVIENVqRSSDEGEYTCTARNQQG-Q 79

                          90
                  ....*....|
gi 568997560  303 EASATLTVRV 312
Cdd:cd20958    80 SASRSVFVKV 89

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 47.93 E-value: 1.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLK--EGFTFLGRDP-----RATIQDQGTLQIKNLRISDTGTYTCVA 494
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvPGKENLIMRPnhvrgNVVVTNIGQLVIYNAQPQDAGLYTCTA 80


                  ....*
gi 568997560  495 TSSSG 499
Cdd:cd05765    81 RNSGG 85

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 47.24 E-value: 1.35e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568997560  438 TALLKCKATGEPLPVISWLKEGfTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05745     4 TVDFLCEAQGYPQPVIAWTKGG-SQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 47.95 E-value: 1.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  426 QGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQG---TLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                  ....*..
gi 568997560  503 WSAVLDV 509
Cdd:cd20973    82 CSAELTV 88

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 47.55 E-value: 1.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  218 ELTVFErptflrrPINQVVLEEEAVEFRCQVQG-DPQPTVRWKKDDADLPRGRYDIKDdyTLRIKKAMSTDEGTYVCIAE 296
Cdd:cd05754     2 QVTVEE-------PRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPSRAMDFNG--ILTIRNVQLSDAGTYVCTGS 72

                          90
                  ....*....|..
gi 568997560  297 NRVGKVEASATL 308
Cdd:cd05754    73 NMLDTDEATATL 84

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.57 E-value: 1.39e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   329 VAQGRTVTFPCETK-GNPQPAVFWQKEGSQNLLfPNQPQQPNSRCSVSPtgdLTITNIQRSDAGYYICQALTVAGSILAK 407
Cdd:pfam00047    8 VLEGDSATLTCSAStGSPGPDVTWSKEGGTLIE-SLKVKHDNGRTTQSS---LLISNVTKEDAGTYTCVVNNPGGSATLS 83


                   ...
gi 568997560   408 AQL 410
Cdd:pfam00047   84 TSL 86

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 48.24 E-value: 1.40e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQ-NLLFPNQPQQpnsrcsvSPTGDLTITNIQ-----RSDAGYY 393
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLlNLVSDERRQQ-------LPNGSLLITSVVhskhnKPDEGFY 76

                          90       100
                  ....*....|....*....|.
gi 568997560  394 ICQA-LTVAGSILA-KAQLEV 412
Cdd:cd05722    77 QCVAqNESLGSIVSrTARVTV 97

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.57 E-value: 1.42e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560   139 PTDVVVAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERISIRGGK----LMISNTRKSDAGMYTCVGTN 207
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqssLLISNVTKEDAGTYTCVVNN 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.39 E-value: 1.48e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560   319 QFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSqnllfpnqpqqpnsrcSVSPTGDLTITNIQRSDAGYYICQA 397
Cdd:pfam13895    1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGS----------------AISSSPNFFTLSVSAEDSGTYTCVA 63

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409363 Cd Length: 102 Bit Score: 48.19 E-value: 1.48e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  231 PINQVVLEEEAVEFRCQVQGDPQPTVRWKK----------DDAD-----LPR-GRYDIKDDYTLRIKKAMSTDEGTYVCI 294
Cdd:cd04974     8 PANQTVVLGSDVEFHCKVYSDAQPHIQWLKhvevngskygPDGLpyvtvLKVaGVNTTGEENTLTISNVTFDDAGEYICL 87

                          90
                  ....*....|....*
gi 568997560  295 AENRVGKVEASATLT 309
Cdd:cd04974    88 AGNSIGLSFHSAWLT 102

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 47.54 E-value: 1.52e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLK-EGFTFlgrdPRATI-QDQGTLQIKNLRISDTGTYTCVATSSS 498
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKvDGSPS----SQWEItTSEPVLEIPNVQFEDEGTYECEAENSR 76


                  .
gi 568997560  499 G 499
Cdd:cd04968    77 G 77

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 47.67 E-value: 1.63e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPrSHRMllpSGSLFFLRIVHGRRSkpdeGSYVCVARNYL 116
Cdd:cd05868     6 PTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDP-SRKV---DGDTIIFSKVQERSS----AVYQCNASNEY 77


                  .
gi 568997560  117 G 117
Cdd:cd05868    78 G 78

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 47.74 E-value: 1.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   29 FPPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETdkddprSHRMLLPS---GSLFFLRIVHgrrsKPDE 105
Cdd:cd05747     2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS------SQRHQITSteyKSTFEISKVQ----MSDE 71

                          90
                  ....*....|...
gi 568997560  106 GSYVCVARNYLGE 118
Cdd:cd05747    72 GNYTVVVENSEGK 84

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 47.74 E-value: 1.83e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCSVSPT---GDLTITNIQRSDAGYY 393
Cdd:cd05747     3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREG--------QIIVSSQRHQITSTeykSTFEISKVQMSDEGNY 74

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 47.51 E-value: 1.93e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  430 NQTLAVDGTALLKCKATGE-PLPVISWLKEGfTFLGRDPRATIQDQGT-----LQIKNLRISDTGTYTCVATSSSGETSW 503
Cdd:cd05750     8 SQTVQEGSKLVLKCEATSEnPSPRYRWFKDG-KELNRKRPKNIKIRNKkknseLQINKAKLEDSGEYTCVVENILGKDTV 86


                  ....*.
gi 568997560  504 SAVLDV 509
Cdd:cd05750    87 TGNVTV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 47.44 E-value: 1.96e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  417 TDRPPPIILQgpinqtlavDG-TALLKCKATGEPLPVISWLKEGFTF--LGRDPRATIqDQGTLQIKNLRISDTGTYTCV 493
Cdd:cd04978     3 IIEPPSLVLS---------PGeTGELICEAEGNPQPTITWRLNGVPIepAPEDMRRTV-DGRTLIFSNLQPNDTAVYQCN 72

                          90
                  ....*....|....*.
gi 568997560  494 ATSSSGETSWSAVLDV 509
Cdd:cd04978    73 ASNVHGYLLANAFLHV 88

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 47.64 E-value: 2.05e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRShrmLLPSGSLFFLRIVHgrrsKPDEGSYVC 110
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLT---LIANGSELHISNVR----YEDTGAYTC 73


                  ....*..
gi 568997560  111 VARNYLG 117
Cdd:cd05736    74 IAKNEGG 80

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 47.14 E-value: 2.56e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCVGTNmvgerDSDPAE 218
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSV-TGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN-----DGDSAQ 81


                  ..
gi 568997560  219 LT 220
Cdd:cd20957    82 AT 83

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 46.41 E-value: 2.68e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  335 VTFPCETKGNPQPAVFWQKEGSQnllfpnqpQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGS 403
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQ--------VTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGY 61

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.62 E-value: 2.93e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   230 RPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPrgrydikDDYTLRIKKAMSTDEGTYVCIAEN-RVGKVEASATL 308
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS-------SSPNFFTLSVSAEDSGTYTCVARNgRGGKVSNPVEL 77


                   ..
gi 568997560   309 TV 310
Cdd:pfam13895   78 TV 79

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 47.23 E-value: 2.99e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEA-VEFRCQVQGDPQPTVRWKKDDADLP--RGRYDIKD-DYTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd05760     1 PVVLKHPASAAEIQPSSrVTLRCHIDGHPRPTYQWFRDGTPLSdgQGNYSVSSkERTLTLRSAGPDDSGLYYCCAHNAFG 80

                          90
                  ....*....|..
gi 568997560  301 KVEASATLTVRV 312
Cdd:cd05760    81 SVCSSQNFTLSI 92

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 46.96 E-value: 3.01e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDD-----ADLPRGRYDIKDDYT-LRIKKAMSTDEGTYVCIAENR 298
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqvistSTLPGVQISFSDGRAkLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 568997560  299 VGKVEASATLTV 310
Cdd:cd20974    81 SGQATSTAELLV 92

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 46.81 E-value: 3.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   36 HPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkdDPRSHRMLLPSGSLFFLRIVhgrrsKPDEGSYVCVARNY 115
Cdd:cd05723     3 KPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVV-----IPSDYFKIVKEHNLQVLGLV-----KSDEGFYQCIAEND 72


                  ....*.
gi 568997560  116 LGEAVS 121
Cdd:cd05723    73 VGNAQA 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 46.78 E-value: 3.24e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  325 RDQIVAQ--GRTVTFPCETKGNPQPAVFWQKEGSqnLLFPNQPQQPNsrcsvSPTGDLTITNIQRSDAGYYICQALTVAG 402
Cdd:cd05856    10 RRRVIARpvGSSVRLKCVASGNPRPDITWLKDNK--PLTPPEIGENK-----KKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

                          90
                  ....*....|
gi 568997560  403 SILAKAQLEV 412
Cdd:cd05856    83 EINATYKVDV 92

Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins. L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1 that involves abnormalities of axonal growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409432 Cd Length: 91 Bit Score: 46.71 E-value: 3.26e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  136 RQNPTDVVVAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERISI-RGGKLMISNTRKSD 197
Cdd:cd05845     1 KEKIDPVEVEEGDPVVLPCNPPKGAPPPRIYWMNSSLEHITQDERVSMgQNGDLYFSNVMEQD 63

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 3.30e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   138 NPTDVVVAAGEPAILECQPPrGHPEPTIYWKKDKVRIDDkeerisirGGKLMISNTRKSDAGMYTCVGTNMVGERDSDPA 217
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAP-GNPPPSYTWYKDGSAISS--------SPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV 75


                   ....
gi 568997560   218 ELTV 221
Cdd:pfam13895   76 ELTV 79

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 46.37 E-value: 4.16e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  248 VQGDPQPTVRWKKDDADL--PRGRYDI---KDDYTLRIKKAMSTDEGTYVCIAENRVGkvEASATLTVRV 312
Cdd:cd05894    19 ISGEPAPTVTWSRGDKAFtaTEGRVRVesyKDLSSFVIEGAEREDEGVYTITVTNPVG--EDHASLFVKV 86

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 46.39 E-value: 4.29e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  137 QNPTDVVVAAGEPAILECQPpRGHPEPTIYWKK-DKVRIDDKEERISirGGKLMISNTRKSDAGMYTCVGTNMVGeRDSD 215
Cdd:cd04968     6 RFPADTYALKGQTVTLECFA-LGNPVPQIKWRKvDGSPSSQWEITTS--EPVLEIPNVQFEDEGTYECEAENSRG-KDTV 81


                  ....*..
gi 568997560  216 PAELTVF 222
Cdd:cd04968    82 QGRIIVQ 88

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 46.61 E-value: 4.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  322 VRPR--DQI-VAQGRTVTFPCETKGNPQPAVFWQKEGSQNLlfpnqPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQAL 398
Cdd:cd20969     4 IRDRkaQQVfVDEGHTVQFVCRADGDPPPAILWLSPRKHLV-----SAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAA 78

                          90
                  ....*....|....
gi 568997560  399 TVAGSILAKAQLEV 412
Cdd:cd20969    79 NAGGNDSMPAHLHV 92

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 46.41 E-value: 4.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPiNQTLAVDGTALLKCKATGEPLPVISWLKEGFTfLGRDPRATIQDQGTLQIKNL-RISDTGTYTCVATSSSG 499
Cdd:cd20958     1 PPFIRPMG-NLTAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPLNHRQRVFPNGTLVIENVqRSSDEGEYTCTARNQQG 78


                  ...
gi 568997560  500 ETS 502
Cdd:cd20958    79 QSA 81

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 46.68 E-value: 5.00e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   324 PRDQIVAQGRTVTFPCETKG---NPQPAVFWQKEGSQN----LLFPNQPQQPNSRCS--VSPTGD-------LTITNIQR 387
Cdd:pfam07686    3 PREVTVALGGSVTLPCTYSSsmsEASTSVYWYRQPPGKgptfLIAYYSNGSEEGVKKgrFSGRGDpsngdgsLTIQNLTL 82

                           90       100
                   ....*....|....*....|....*..
gi 568997560   388 SDAGYYICQALTVAGSIL-AKAQLEVT 413
Cdd:pfam07686   83 SDSGTYTCAVIPSGEGVFgKGTRLTVL 109

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 46.01 E-value: 6.30e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCS----VSPTGDLT----ITNIQRS 388
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDG--------FPIPESPRFRvgdyVTSDGDVVsyvnISSVRVE 72

                          90       100
                  ....*....|....*....|....
gi 568997560  389 DAGYYICQALTVAGSILAKAQLEV 412
Cdd:cd20956    73 DGGEYTCTATNDVGSVSHSARINV 96

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 46.04 E-value: 6.46e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  425 LQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTF--LGRDPRATIQdQGTLQIKNLRISDTGTYTCVATSSSG 499
Cdd:cd05867     3 TRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIegTDPDPRRHVS-SGALILTDVQPSDTAVYQCEARNRHG 78

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 46.10 E-value: 6.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  231 PINQVVLEEEAVE------FRCQVQGDPQPTVRWKKDDADLprgRYDIKDDYTL-------RIKKAMSTDEGTYVCIAEN 297
Cdd:cd05736     1 PVIRVYPEFQAKEpgveasLRCHAEGIPLPRVQWLKNGMDI---NPKLSKQLTLiangselHISNVRYEDTGAYTCIAKN 77

                          90
                  ....*....|...
gi 568997560  298 RVGKVEASATLTV 310
Cdd:cd05736    78 EGGVDEDISSLFV 90

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 46.10 E-value: 6.73e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIV---SKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprshRMLLPSGSLfflrIVHGRRSKPDEGS 107
Cdd:cd05849     2 PVFEEQPIDTIYpeeSTEGKVSVNCRARANPFPIYKWRKNNLDIDLTND-----RYSMVGGNL----VINNPDKYKDAGR 72

                          90
                  ....*....|....*....
gi 568997560  108 YVCVARNYLGEAVSRNASL 126
Cdd:cd05849    73 YVCIVSNIYGKVRSREATL 91

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 45.62 E-value: 7.57e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRML-LPSGSLfflrivhgrrskPDEGSY 108
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEPVLeIPNVQF------------EDEGTY 68

                          90
                  ....*....|....
gi 568997560  109 VCVARNYLGEAVSR 122
Cdd:cd04968    69 ECEAENSRGKDTVQ 82

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 45.63 E-value: 7.60e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  321 VVRPRDQIVAQGRTVTFPCETKG-NPQPAVFWQKEGSQnllFPNQPQQPNsrcsvsptGDLTITNIQRSDAGYYIC 395
Cdd:cd05754     5 VEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGT---LPSRAMDFN--------GILTIRNVQLSDAGTYVC 69

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 45.27 E-value: 8.69e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  440 LLKCKATGEPLPVISWLKEGFTFLGRDPRATIQDQgTLQIKNLRISDTGTYTCVATSSSGETSWSAVL 507
Cdd:cd05723    16 VFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEH-NLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 45.17 E-value: 9.18e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  332 GRTVTFPCETKGNPQPAVFWQkegsqnLLFPNQPQQPnsRCSVSP---TGDLTITNIQRSDAGYYICQALTVAGSILA 406
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWR------LNWGHVPDSA--RVSITSeggYGTLTIRDVKESDQGAYTCEAINTRGMVFG 70

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 45.55 E-value: 9.30e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997560  432 TLAVDGTA-LLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQDQGTLQIKNLRIS-----DTGTYTCVAT 495
Cdd:cd05722    11 IVAMRGGPvVLNCSAESDPPPKIEWKKDGVLLnLVSDERRQQLPNGSLLITSVVHSkhnkpDEGFYQCVAQ 81

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 45.65 E-value: 9.59e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEE-RISIRGG--KLMISNTRKSDAGMYTCVGTNMVGe 211
Cdd:cd20972     4 FIQKLRSQEVAEGSKVRLECRV-TGNPTPVVRWFCEGKELQNSPDiQIHQEGDlhSLIIAEAFEEDTGRYSCLATNSVG- 81

                          90
                  ....*....|
gi 568997560  212 RDSDPAELTV 221
Cdd:cd20972    82 SDTTSAEIFV 91

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 45.46 E-value: 9.68e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  142 VVVAAGEPAILECQPpRGHPEPTIYW---KKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVGErDSDPAE 218
Cdd:cd20969    12 VFVDEGHTVQFVCRA-DGDPPPAILWlspRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGN-DSMPAH 89


                  ...
gi 568997560  219 LTV 221
Cdd:cd20969    90 LHV 92

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 45.56 E-value: 1.08e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTAL-LKCKATGEPLPV-ISWLKE--------GFTFLGRDPRATIqdqgtLQIKNLRISDTGTY 490
Cdd:cd20959     1 PPRIIPFAFGEGAAQVGMRAqLHCGVPGGDLPLnIRWTLDgqpisddlGITVSRLGRRSSI-----LSIDSLEASHAGNY 75

                          90
                  ....*....|....*....
gi 568997560  491 TCVATSSSGETSWSAVLDV 509
Cdd:cd20959    76 TCHARNSAGSASYTAPLTV 94

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 45.10 E-value: 1.11e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560   651 LTPTTVQVTWTVDRQPQF-IQGYRVMYRQTSGLQAsTVWQNLDakvPTERSAVLVNLKKGVTYEIKVR 717
Cdd:pfam00041   11 VTSTSLTVSWTPPPDGNGpITGYEVEYRPKNSGEP-WNEITVP---GTTTSVTLTGLKPGTEYEVRVQ 74

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409452 Cd Length: 93 Bit Score: 45.43 E-value: 1.20e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  433 LAVDGTALLKCKATGEPLPvISWLKEGFTFLGRDPRATIQDQGT---LQIKNLRISDTGTYTCVATSSSGETSWSAVL 507
Cdd:cd05866    12 LSVGESKFFTCTAIGEPES-IDWYNPQGEKIVSSQRVVVQKEGVrsrLTIYNANIEDAGIYRCQATDAKGQTQEATVV 88

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 45.09 E-value: 1.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRGRYD--IKDD--YTLRIKKAMSTDEGTYVCIAENRV 299
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIrPDSAHKmlVRENgvHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 568997560  300 GKVEASATLTV 310
Cdd:cd20990    81 GQNSFNLELVV 91

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 45.56 E-value: 1.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWK-KDDADLPR--------GRYDIKDDYTLRIKKAMSTDEGTYVCIA 295
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKhSKGSGVPQfqhivplnGRIQLLSNGSLLIKHVLEEDSGYYLCKV 81

                          90
                  ....*....|....*.
gi 568997560  296 ENRVGK-VEASATLTV 310
Cdd:cd05734    82 SNDVGAdISKSMYLTV 97

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 45.42 E-value: 1.38e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKGNPQP--AVFWQKEGsqnllFPNQPQQPNS---RCSVSPT-GDLTITNIQRSDAGYYICQA 397
Cdd:cd05854     9 PSSADINQGENLTLQCHASHDPTMdlTFTWSLDD-----FPIDLDKPNGhyrRMEVKETiGDLVIVNAQLSHAGTYTCTA 83

                          90       100
                  ....*....|....*....|....*
gi 568997560  398 LTVAGSILAKAQLEVtdvltdRPPP 422
Cdd:cd05854    84 QTVVDSASASATLVV------RGPP 102

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 44.79 E-value: 1.39e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  438 TALLKCKATGEPLPVISWlKEGFTFLGRDPRATIQD---QGTLQIKNLRISDTGTYTCVATSSSG 499
Cdd:cd05743     3 TVEFTCVATGVPTPIINW-RLNWGHVPDSARVSITSeggYGTLTIRDVKESDQGAYTCEAINTRG 66

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 44.87 E-value: 1.62e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  325 RDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNSRCSVSPTGD----LTITNIQRSDAGYYICQALTV 400
Cdd:cd20973     5 RDKEVVEGSAARFDCKVEGYPDPEVKWMKDD--------NPIVESRRFQIDQDEDglcsLIISDVCGDDSGKYTCKAVNS 76

                          90
                  ....*....|..
gi 568997560  401 AGSILAKAQLEV 412
Cdd:cd20973    77 LGEATCSAELTV 88

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 44.51 E-value: 1.62e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  428 PINQTLAVDGTALLKCKATGEPLPVISWLKeGFTFLGRDPRATIqDQGTLQIKNlrISDTGTYTCVATSSSGETSWSAVL 507
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMK-GGEELTKEDEMPV-GRNVLELTN--IYESANYTCVAISSLGMIEATAQV 79


                  ..
gi 568997560  508 DV 509
Cdd:cd05739    80 TV 81

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 44.87 E-value: 1.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  136 RQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKD--------KVRIDDKEERISirggKLMISNTRKSDAGMYTCVGTN 207
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKV-EGYPDPEVKWMKDdnpivesrRFQIDQDEDGLC----SLIISDVCGDDSGKYTCKAVN 75

                          90
                  ....*....|....
gi 568997560  208 MVGERDSDpAELTV 221
Cdd:cd20973    76 SLGEATCS-AELTV 88

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 44.85 E-value: 1.75e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKD---------DADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIA 295
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQvpgkenlimRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80

                          90
                  ....*....|....*
gi 568997560  296 ENRVGKVEASATLTV 310
Cdd:cd05765    81 RNSGGLLRANFPLSV 95

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 44.70 E-value: 1.80e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQ-DQGTLQIKNLRISDT---GTYTCVAT 495
Cdd:cd05733     1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFdPAKDPRVSMRrRSGTLVIDNHNGGPEdyqGEYQCYAS 80


                  ....
gi 568997560  496 SSSG 499
Cdd:cd05733    81 NELG 84

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 44.71 E-value: 1.88e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKD--KVRIDDKEERISIRGG--KLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd20990     3 FLQAPGDLTVQEGKLCRMDCKV-SGLPTPDLSWQLDgkPIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAG 81

                          90
                  ....*....|.
gi 568997560  211 ErDSDPAELTV 221
Cdd:cd20990    82 Q-NSFNLELVV 91

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 44.95 E-value: 1.90e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   34 VEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERV---ETDKDDPRSHRMLLPSGSlffLRIVHGRRSkpDEGSYVC 110
Cdd:cd05726     3 VVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNllfPYQPPQPSSRFSVSPTGD---LTITNVQRS--DVGYYIC 77

                          90
                  ....*....|....*...
gi 568997560  111 VARNYLGEAVSRnASLEV 128
Cdd:cd05726    78 QALNVAGSILAK-AQLEV 94

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 44.48 E-value: 1.96e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPT-IEWYKDGERVETDKDDPRSHRmllPSGSLFFLrivhgRRSKPDEGSYV 109
Cdd:cd20979     1 PVLKEQPAEVLFREGQPTVLECVTEGGDQGVkYSWLKDGKSFNWQEHNVAQRK---DEGSLVFL-----KPQASDEGQYQ 72

                          90
                  ....*....|....*..
gi 568997560  110 CVARNYLGEAVSRNASL 126
Cdd:cd20979    73 CFAETPAGVASSRVISF 89

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 44.39 E-value: 1.99e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  329 VAQGRTVTFPCETKGNPQPAVFWQkeGSQNLLFPNqpqqpNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGSILAKA 408
Cdd:cd05764    12 VLEGQRATLRCKARGDPEPAIHWI--SPEGKLISN-----SSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARV 84


                  ....
gi 568997560  409 QLEV 412
Cdd:cd05764    85 ELHI 88

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 44.76 E-value: 2.04e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDdprshRMLLPSGSLFFLRIVHGRRSKPDEGSYVC 110
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTD-----RISLYQDNCGRICLLIQNANKKDAGWYTV 75

                          90
                  ....*....|....*...
gi 568997560  111 VARNYLGeAVSRNASLEV 128
Cdd:cd05892    76 SAVNEAG-VVSCNARLDV 92

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 44.11 E-value: 2.43e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  322 VRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLlfpnqpqqPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVA 401
Cdd:cd05723     2 KKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVI--------PSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDV 73


                  ....*....
gi 568997560  402 GSILAKAQL 410
Cdd:cd05723    74 GNAQASAQL 82

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 44.24 E-value: 2.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   32 RIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRmLLPSGSLFflrivhGRRSKPDEGSYVCV 111
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYR-ILADGLLI------NKVTQDDTGEYTCR 73


                  ....*...
gi 568997560  112 ARNYLGEA 119
Cdd:cd20949    74 AYQVNSIA 81

Second immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 44.55 E-value: 2.66e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  147 GEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERISIR------GGKLMISNTRKSDAG---MYTCVGTN 207
Cdd:cd20965    17 GKPFKLDCNVPPGYPKPTIEWKKQLVSDSSKADTILDRritispNGDLYFTNVTKEDVStdyKYVCVAKT 86

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 44.06 E-value: 2.67e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECqPPRGHPEPTIYWKKDKVRIDDKEERISIRGGK----LMISNTRKSDAGMYTCVGTNMVGErds 214
Cdd:cd05894     2 ENTIVVVAGNKLRLDV-PISGEPAPTVTWSRGDKAFTATEGRVRVESYKdlssFVIEGAEREDEGVYTITVTNPVGE--- 77


                  ....*..
gi 568997560  215 DPAELTV 221
Cdd:cd05894    78 DHASLFV 84

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 44.63 E-value: 2.78e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  136 RQNPTDVVVAAGEPAILEC---------------QPPRGHPEPTIYWKKDK-VRIDDKEERISIRGGK-----LMISNTR 194
Cdd:cd00099     2 TQSPRSLSVQEGESVTLSCevsssfsstyiywyrQKPGQGPEFLIYLSSSKgKTKGGVPGRFSGSRDGtssfsLTISNLQ 81

                          90
                  ....*....|
gi 568997560  195 KSDAGMYTCV 204
Cdd:cd00099    82 PEDSGTYYCA 91

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 44.24 E-value: 2.79e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRI-----DDKEERISIRGgkLMISNTRKSDAGMYTCVGTNMV 209
Cdd:cd20949     2 FTENAYVTTVKEGQSATILCEV-KGEPQPNVTWHFNGQPIsasvaDMSKYRILADG--LLINKVTQDDTGEYTCRAYQVN 78

                          90
                  ....*....|..
gi 568997560  210 GERdSDPAELTV 221
Cdd:cd20949    79 SIA-SDMQERTV 89

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 44.13 E-value: 2.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  236 VLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRGRYDIKDDY----TLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05891    13 IMEGKTLNLTCTVFGNPDPEVIWFKNDQDIeLSEHYSVKLEQgkyaSLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 44.13 E-value: 2.88e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  144 VAAGEPAILECqPPRGHPEPTIYWKKDKVRIDdKEERISI-----RGGKLMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd05729    16 LPAANKVRLEC-GAGGNPMPNITWLKDGKEFK-KEHRIGGtkveeKGWSLIIERAIPRDKGKYTCIVENEYGS 86

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 44.16 E-value: 2.90e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQG---RTVTFPCETKGNPQPAVFWQKEGSQNLLfpnqpqQPNSRCSVSpTGDLTITN-IQRSDAGYY 393
Cdd:cd04967     2 PVFEEQPDDTIFPEDsdeKKVALNCRARANPVPSYRWLMNGTEIDL------ESDYRYSLV-DGTLVISNpSKAKDAGHY 74

                          90
                  ....*....|....
gi 568997560  394 ICQALTVAGSILAK 407
Cdd:cd04967    75 QCLATNTVGSVLSR 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 44.20 E-value: 2.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  233 NQVVLE-EEAVEFRCQVQGDPQPTVRWK------KDDADLPRGRYDIKDDY---TLRIKKAMSTDEGTYVCIAENRVGKV 302
Cdd:cd05869    10 NQTAMElEEQITLTCEASGDPIPSITWRtstrniSSEEKTLDGHIVVRSHArvsSLTLKYIQYTDAGEYLCTASNTIGQD 89


                  ....*...
gi 568997560  303 EASATLTV 310
Cdd:cd05869    90 SQSMYLEV 97

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 44.16 E-value: 3.01e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRP---INQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLprgryDIKDDY-------TLRIKKAMST-DEGTYVC 293
Cdd:cd05848     2 PVFVQEPddaIFPTDSDEKKVILNCEARGNPVPTYRWLRNGTEI-----DTESDYryslidgNLIISNPSEVkDSGRYQC 76


                  ....*....
gi 568997560  294 IAENRVGKV 302
Cdd:cd05848    77 LATNSIGSI 85

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 44.10 E-value: 3.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  141 DVVVAAGEPAILECqPPRGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISN-TRKSDAGMYTCVGTNMVGERDSDPAEL 219
Cdd:cd20958     9 NLTAVAGQTLRLHC-PVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENvQRSSDEGEYTCTARNQQGQSASRSVFV 87


                  ..
gi 568997560  220 TV 221
Cdd:cd20958    88 KV 89

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 44.18 E-value: 3.31e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRI-------DDKEERISI-RGGKLMISNTRKSDAGMYTCVGT 206
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCET-KGNPQPAIFWQKEGSQNllfpyqpPQPSSRFSVsPTGDLTITNVQRSDVGYYICQAL 80


                  ....
gi 568997560  207 NMVG 210
Cdd:cd05726    81 NVAG 84

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 44.17 E-value: 3.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQnlLFPNQPQQPNSRCSVSptgDLTITNIQRSDAGYYICQA 397
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMD--INPKLSKQLTLIANGS---ELHISNVRYEDTGAYTCIA 75


                  ....*
gi 568997560  398 LTVAG 402
Cdd:cd05736    76 KNEGG 80

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 44.08 E-value: 3.51e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPNQPQQPNSRCSVSPT-GDLTITNIQRSDAGYYIC 395
Cdd:cd04970     2 ATRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVPIDLEKIEGHYRRRYGKDSnGDLEIVNAQLKHAGRYTC 81

                          90       100
                  ....*....|....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEVtdvltdRPPP 422
Cdd:cd04970    82 TAQTVVDSDSASATLVV------RGPP 102

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 44.16 E-value: 3.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQ---TLAVDGTALLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQDqGTLQIKN-LRISDTGTYTCVATS 496
Cdd:cd04967     2 PVFEEQPDDTifpEDSDEKKVALNCRARANPVPSYRWLMNGTEIdLESDYRYSLVD-GTLVISNpSKAKDAGHYQCLATN 80


                  ...
gi 568997560  497 SSG 499
Cdd:cd04967    81 TVG 83

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 44.57 E-value: 3.74e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  425 LQGPINQTLAVDGTALLKCKATGEPLPVISWLkegftFLGRDPRATI--------QDQ------------GTLQIKNLRI 484
Cdd:cd20940     4 IKSPLSQQRLVGDSVELHCEAVGSPIPEIQWW-----FEGQEPNEICsqlwdgarLDRvhinatyhqhatSTISIDNLTE 78

                          90
                  ....*....|..
gi 568997560  485 SDTGTYTCVATS 496
Cdd:cd20940    79 EDTGTYECRASN 90

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 43.37 E-value: 4.08e-05

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997560    652 TPTTVQVTWTV---DRQPQFIQGYRVMYRQTSGlqastVWQNLDaKVPTERSAVLVNLKKGVTYEIKVRPY 719
Cdd:smart00060   13 TSTSVTLSWEPppdDGITGYIVGYRVEYREEGS-----EWKEVN-VTPSSTSYTLTGLKPGTEYEFRVRAV 77

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 43.83 E-value: 4.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQ--IVAQGRTVTFPCETKGNPQPAVFWQKeGSQNLLfpnqpqqPNSRCSVSPTGDLTITNIQRSDAGYYIC 395
Cdd:cd05852     1 PTFEFNPMKKkiLAAKGGRVIIECKPKAAPKPKFSWSK-GTELLV-------NNSRISIWDDGSLEILNITKLDEGSYTC 72

                          90
                  ....*....|....*..
gi 568997560  396 QALTVAGSILAKAQLEV 412
Cdd:cd05852    73 FAENNRGKANSTGVLSV 89

Immunoglobulin V-Type;

Pssm-ID: 214650 Cd Length: 81 Bit Score: 43.52 E-value: 4.17e-05

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560    438 TALLKCKATG--EPLPVISWLKE----GFTFLGRDP-------------RATI-----QDQGTLQIKNLRISDTGTYTC 492
Cdd:smart00406    1 SVTLSCKFSGstFSSYYVSWVRQppgkGLEWLGYIGsngssyyqesykgRFTIskdtsKNDVSLTISNLRVEDTGTYYC 79

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 43.45 E-value: 4.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPT--DVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEeRISI-RGGKLMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd05852     3 FEFNPMkkKILAAKGGRVIIECKP-KAAPKPKFSWSKGTELLVNNS-RISIwDDGSLEILNITKLDEGSYTCFAENNRGK 80


                  ...
gi 568997560  212 RDS 214
Cdd:cd05852    81 ANS 83

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 43.69 E-value: 5.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLP--VISWLKEGFTF-----LGRDPRATIQDQ-GTLQIKNLRISDTGTYTC 492
Cdd:cd04970     2 ATRITLAPSNADITVGENATLQCHASHDPTLdlTFTWSFNGVPIdlekiEGHYRRRYGKDSnGDLEIVNAQLKHAGRYTC 81

                          90
                  ....*....|....*..
gi 568997560  493 VATSSSGETSWSAVLDV 509
Cdd:cd04970    82 TAQTVVDSDSASATLVV 98

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 43.40 E-value: 5.33e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568997560  147 GEPAILECQPpRGHPEPTIYWKKDKVRIDDKEER---ISIRGGKLMISNTRKSDAGMYTCVGTNMVGeRDSDPAELTV 221
Cdd:cd05736    15 GVEASLRCHA-EGIPLPRVQWLKNGMDINPKLSKqltLIANGSELHISNVRYEDTGAYTCIAKNEGG-VDEDISSLFV 90

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 43.50 E-value: 5.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLfpnqPQQPNSRCSVSP-TGDLTITNIQRSDAGYYICQ 396
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIST----STLPGVQISFSDgRAKLSIPAVTKANSGRYSLT 76

                          90
                  ....*....|....*..
gi 568997560  397 ALTVAGSILAKAQLEVT 413
Cdd:cd20974    77 ATNGSGQATSTAELLVL 93

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 43.67 E-value: 5.44e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  325 RDQIVAQGRTVTFPCETKGNPQPAVFWqKEGSQNllFPNQPQQPNSRCSVSP---TGDLTITNIQRSDAGYYICQALTVA 401
Cdd:cd05732     9 ENQTAVELEQITLTCEAEGDPIPEITW-RRATRG--ISFEEGDLDGRIVVRGharVSSLTLKDVQLTDAGRYDCEASNRI 85

                          90
                  ....*....|.
gi 568997560  402 GSILAKAQLEV 412
Cdd:cd05732    86 GGDQQSMYLEV 96

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 42.97 E-value: 5.58e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  231 PINQVVLEEEAVEFRCQVQGDPQPTVRWKK------DDADLPRGRydikddYTLRIKKAMstDEGTYVCIAENRVGKVEA 304
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMKggeeltKEDEMPVGR------NVLELTNIY--ESANYTCVAISSLGMIEA 75


                  ....*..
gi 568997560  305 SATLTVR 311
Cdd:cd05739    76 TAQVTVK 82

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 43.23 E-value: 5.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKD----DADLPRGRYDIKDDYT-LRIKKAMSTDEGTYVCIAENRV 299
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNrqpvRPDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 568997560  300 GKVEASATLTV 310
Cdd:cd20975    81 GARQCEARLEV 91

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 43.11 E-value: 6.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRIDDKEE---RISIRGG--KLMISNTRKSDAGMYTCVGTNMV 209
Cdd:cd20974     3 FTQPLQSVVVLEGSTATFEAHV-SGKPVPEVSWFRDGQVISTSTLpgvQISFSDGraKLSIPAVTKANSGRYSLTATNGS 81

                          90
                  ....*....|..
gi 568997560  210 GERDSdPAELTV 221
Cdd:cd20974    82 GQATS-TAELLV 92

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 42.96 E-value: 6.94e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   34 VEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHrmlLPSGSLFFLRIvhgrrSKPDEGSYVCVAR 113
Cdd:cd05867     3 TRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRH---VSSGALILTDV-----QPSDTAVYQCEAR 74


                  ....
gi 568997560  114 NYLG 117
Cdd:cd05867    75 NRHG 78

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 43.16 E-value: 6.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  137 QNPTDVVVAAGEPAILECQPpRGHPEPTIYWKKDKVRID-DKEERISIR--GGKLMISNTR---KSDAGMYTCVGTNMVG 210
Cdd:cd05733     6 QSPKDYIVDPRDNITIKCEA-KGNPQPTFRWTKDGKFFDpAKDPRVSMRrrSGTLVIDNHNggpEDYQGEYQCYASNELG 84


                  ....*....
gi 568997560  211 ERDSDPAEL 219
Cdd:cd05733    85 TAISNEIRL 93

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 42.62 E-value: 7.29e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560   44 KGEPTTLNCKAEGRPTPTIEWYKDGERVETDkddpRSHrMLLPSGSLFFLRI-VHgrrskpDEGSYVCVARNYLG 117
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVD----RRH-LVLSSGTLRISRVaLH------DQGQYECQAVNIVG 64

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 43.01 E-value: 7.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGP---INQTLAVDGTALLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQDqGTLQIKNL-RISDTGTYTCVATS 496
Cdd:cd05848     2 PVFVQEPddaIFPTDSDEKKVILNCEARGNPVPTYRWLRNGTEIdTESDYRYSLID-GNLIISNPsEVKDSGRYQCLATN 80


                  ...
gi 568997560  497 SSG 499
Cdd:cd05848    81 SIG 83

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 42.91 E-value: 7.46e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  432 TLAVDGTALLKCKATGEPLPVISWLK--EGFTflgRDPRATIQDQ-----GTLQIKNLRISDTGTYTCVATSSSGETSWS 504
Cdd:cd20953    14 TVSSASSIALLCPAQGYPAPSFRWYKfiEGTT---RKQAVVLNDRvkqvsGTLIIKDAVVEDSGKYLCVVNNSVGGESVE 90


                  ....*
gi 568997560  505 AVLDV 509
Cdd:cd20953    91 TVLTV 95

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.78 E-value: 7.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDP-RATIQDQG--TLQIKNLRISDTGTYTCVATSSS 498
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAhKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 568997560  499 GETSWSAVLDV 509
Cdd:cd20990    81 GQNSFNLELVV 91

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 42.57 E-value: 8.03e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560    37 PSDVIVSKGEPTTLNCKA-EGRPTPTIEWYKDGERVET---DKDDPRSHRmllpSGSLFFLRIvhgrrSKPDEGSYVCVA 112
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIEslkVKHDNGRTT----QSSLLISNV-----TKEDAGTYTCVV 73

                           90
                   ....*....|
gi 568997560   113 RNYLGEAVSR 122
Cdd:pfam00047   74 NNPGGSATLS 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 42.92 E-value: 8.44e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  438 TALLKCKATGEPLPVISWLKEGFTFLGRDPRATI---QDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05857    21 TVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIGGYkvrNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 42.78 E-value: 8.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL-PRG-RYDIKDDY--TLRIKKAMST--DEGTYVCIAENR 298
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQIsPKSdHYTIQRDLdgTCSLHTTASTldDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 568997560  299 VGKVEASATLTV 310
Cdd:cd05893    81 QGRISCTGRLMV 92

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 42.66 E-value: 9.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPNQPqqpnsrcSVSPTGDLTI-TNIQRSDAGYYICQAL 398
Cdd:cd05868     2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDP-------SRKVDGDTIIfSKVQERSSAVYQCNAS 74

                          90
                  ....*....|....
gi 568997560  399 TVAGSILAKAQLEV 412
Cdd:cd05868    75 NEYGYLLANAFVNV 88

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 42.19 E-value: 9.32e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  446 TGEPLPVISWLKEGfTFLGRDPRATIQ---DQGTLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd05748    17 KGRPTPTVTWSKDG-QPLKETGRVQIEttaSSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 42.70 E-value: 1.05e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 568997560  163 PTIYWKKDKVRIDDkEERISIRGGKLMISNTRKSDAGMYTCVGT 206
Cdd:cd05757    30 PPIQWYKDCKPLQG-DKRFIPKGSKLLIQNVTEEDAGNYTCKFT 72

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 42.32 E-value: 1.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkddPRSHRMLLPSGSLFFLRIvhgrrSKPDEGSYV 109
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM------PATAEISMSGAVLKIFNI-----QPEDEGTYE 69


                  ....*...
gi 568997560  110 CVARNYLG 117
Cdd:cd05851    70 CEAENIKG 77

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 42.83 E-value: 1.11e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   137 QNPTDVVVAAGEPAILECQPPRGHPEPT--IYWKKDKVRIDD---------------KEERISIRGGK------LMISNT 193
Cdd:pfam07686    1 QTPREVTVALGGSVTLPCTYSSSMSEAStsVYWYRQPPGKGPtfliayysngseegvKKGRFSGRGDPsngdgsLTIQNL 80

                           90       100
                   ....*....|....*....|....*...
gi 568997560   194 RKSDAGMYTCVGTNMVGERDSDPAELTV 221
Cdd:pfam07686   81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 42.92 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPPRGHP-EPTIYWKKDKVRIDDKEERISIR-------GGKLMISNTRKSDAGMYTCVGTNMVg 210
Cdd:cd04970     9 PSNADITVGENATLQCHASHDPTlDLTFTWSFNGVPIDLEKIEGHYRrrygkdsNGDLEIVNAQLKHAGRYTCTAQTVV- 87

                          90
                  ....*....|.
gi 568997560  211 ERDSDPAELTV 221
Cdd:cd04970    88 DSDSASATLVV 98

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 42.57 E-value: 1.13e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  227 FLRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADL----PRGRYDIKDDyTLRIKKAMSTDEGTYVCIAENRVGKV 302
Cdd:cd05867     2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIegtdPDPRRHVSSG-ALILTDVQPSDTAVYQCEARNRHGNL 80


                  ....*...
gi 568997560  303 EASATLTV 310
Cdd:cd05867    81 LANAHVHV 88

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 42.73 E-value: 1.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  424 ILQGPINQTLAVDG-TALLKCKATGEPLPVISWLKEG-FTFLGRDPRATIQ---DQGTLQIKNLRISDTGTYTCVATSSS 498
Cdd:cd20974     2 VFTQPLQSVVVLEGsTATFEAHVSGKPVPEVSWFRDGqVISTSTLPGVQISfsdGRAKLSIPAVTKANSGRYSLTATNGS 81

                          90
                  ....*....|..
gi 568997560  499 GETSWSAVLDVT 510
Cdd:cd20974    82 GQATSTAELLVL 93

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.31 E-value: 1.35e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997560  246 CQVQGDPQPTVRWKKD----DADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVG-KVEASATLTVR 311
Cdd:cd05738    21 CAASGNPDPEISWFKDflpvDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGtRYSAPANLYVR 91

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 42.48 E-value: 1.40e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   29 FPPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKdGERVETDKDDPRSHRMLLPSGS--LFFLRIVHGRRSkpDEG 106
Cdd:cd05735     2 IPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEK-EDTIINPSEMSRYLVTTKEVGDevISTLQILPTVRE--DSG 78

                          90
                  ....*....|..
gi 568997560  107 SYVCVARNYLGE 118
Cdd:cd05735    79 FFSCHAINSYGE 90

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.81 E-value: 1.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  142 VVVAAGEPAILECqPPRGHPEPTIYWKKDKVRIDDKeERISIRGG----KLMISNTRKSDAGMYTCVGTNMVGErdsDPA 217
Cdd:cd05748     2 IVVRAGESLRLDI-PIKGRPTPTVTWSKDGQPLKET-GRVQIETTasstSLVIKNAKRSDSGKYTLTLKNSAGE---KSA 76


                  ....
gi 568997560  218 ELTV 221
Cdd:cd05748    77 TINV 80

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.01 E-value: 1.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQPQQPNS--RCSVSPTG--DLTITNIQRSDAGYY 393
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDG--------KPIRPDSahKMLVRENGvhSLIIEPVTSRDAGIY 72


                  ....*....
gi 568997560  394 ICQALTVAG 402
Cdd:cd20990    73 TCIATNRAG 81

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.93 E-value: 1.54e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  237 LEEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTVR 311
Cdd:cd05851    14 LKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 42.01 E-value: 1.63e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560   42 VSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRMLLPSGSLfflrivHGRRSK-PDEGSYVCVARNYLG 117
Cdd:cd05893    12 IFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCSL------HTTASTlDDDGNYTIMAANPQG 82

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 42.27 E-value: 1.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  233 NQVVLEEEAVEFRCQVQGDPQPTVRWKK--------DDADLPRGRYDIKDDY---TLRIKKAMSTDEGTYVCIAENRVGK 301
Cdd:cd05870    10 NETTVENGAATLSCKAEGEPIPEITWKRasdghtfsEGDKSPDGRIEVKGQHgesSLHIKDVKLSDSGRYDCEAASRIGG 89


                  ....*....
gi 568997560  302 VEASATLTV 310
Cdd:cd05870    90 HQKSMYLDI 98

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 409416 Cd Length: 98 Bit Score: 42.05 E-value: 1.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSdVIVSKGEPTTLNCKAEG-RPTPTIEWYKDGERVetdkDDPRSHRMLLPSG----SLFFLRIVhgrRSKPDE 105
Cdd:cd05759     2 PVIEGGPV-ISLQAGVPYNLTCRARGaKPAAEIIWFRDGEQL----EGAVYSKELLKDGkretTVSTLLIT---PSDLDT 73

                          90
                  ....*....|
gi 568997560  106 G-SYVCVARN 114
Cdd:cd05759    74 GrTFTCRARN 83

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 41.78 E-value: 2.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdkddPRSHRMLL-----PSGSLF-FLRIVHGRRSkp 103
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPI------PESPRFRVgdyvtSDGDVVsYVNISSVRVE-- 72

                          90
                  ....*....|....*..
gi 568997560  104 DEGSYVCVARNYLGEAV 120
Cdd:cd20956    73 DGGEYTCTATNDVGSVS 89

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 41.71 E-value: 2.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  134 DFRQNPTDVvvaaGEPAILECQPPRGHPEPTIYWKKDKVRIDD----KEERISIRGGKLMISNTRKSDAGMYTCVGTNMV 209
Cdd:cd20959     8 AFGEGAAQV----GMRAQLHCGVPGGDLPLNIRWTLDGQPISDdlgiTVSRLGRRSSILSIDSLEASHAGNYTCHARNSA 83

                          90
                  ....*....|..
gi 568997560  210 GERdSDPAELTV 221
Cdd:cd20959    84 GSA-SYTAPLTV 94

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 41.01 E-value: 2.17e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568997560  158 RGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd05746     8 QGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIG 60

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 41.89 E-value: 2.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  321 VVRPRDQIVAQGRTVTFPCETKGNPQPAVFWqKEGSQNLLFPNQPQQPNSRCSVS---PTGDLTITNIQRSDAGYYICQA 397
Cdd:cd05870     5 IIQLKNETTVENGAATLSCKAEGEPIPEITW-KRASDGHTFSEGDKSPDGRIEVKgqhGESSLHIKDVKLSDSGRYDCEA 83


                  ....*
gi 568997560  398 LTVAG 402
Cdd:cd05870    84 ASRIG 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 41.23 E-value: 2.63e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   428 PINQTLAVDGTALLKCKATGEPLPVISWLKEGftflgrdprATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSwSAVL 507
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG---------SAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKV-SNPV 75


                   ...
gi 568997560   508 DVT 510
Cdd:pfam13895   76 ELT 78

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 41.62 E-value: 2.73e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQnlLFPNQPQQPNSRcSVSPTGDLTITNIQRSDAGYYICQA 397
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQ--ISPKSDHYTIQR-DLDGTCSLHTTASTLDDDGNYTIMA 77

                          90
                  ....*....|....*
gi 568997560  398 LTVAGSILAKAQLEV 412
Cdd:cd05893    78 ANPQGRISCTGRLMV 92

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 41.00 E-value: 2.92e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  139 PTDVVVAAGEPAILECQPPRGHPEPTIYWkkdkVRIDDK-EERISIRGGKLMISNTRKSDAGMYTCVGTNMvgeRDSDPA 217
Cdd:cd05754     8 PRSQEVRPGADVSFICRAKSKSPAYTLVW----TRVNGTlPSRAMDFNGILTIRNVQLSDAGTYVCTGSNM---LDTDEA 80


                  ....*
gi 568997560  218 ELTVF 222
Cdd:cd05754    81 TATLY 85

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 41.42 E-value: 2.98e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  236 VLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRG-RYDIK----DDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd05737    13 IMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLdHCNLKveagRTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 41.50 E-value: 3.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  335 VTFPCETKGNPQPAVFWqKEGSQNllFPNQPQQPNSRCSVSP---TGDLTITNIQRSDAGYYICQALTVAGSILAKAQLE 411
Cdd:cd05869    20 ITLTCEASGDPIPSITW-RTSTRN--ISSEEKTLDGHIVVRSharVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLE 96


                  .
gi 568997560  412 V 412
Cdd:cd05869    97 V 97

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 41.38 E-value: 3.00e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568997560  159 GHPEPTIYWKKDKVRIDDKEERISIRGG-KLMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd05856    30 GNPRPDITWLKDNKPLTPPEIGENKKKKwTLSLKNLKPEDSGKYTCHVSNRAGE 83

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 41.45 E-value: 3.08e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLE---EEAVEFRCQVQGDPQPTVRWKKDDADL---PRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENR 298
Cdd:cd05850     3 PVFEEQPSSTLFPEgsaEEKVTLACRARASPPATYRWKMNGTELkmePDSRYRLVAGNLVISNPVKAKDAGSYQCLASNR 82


                  ....
gi 568997560  299 VGKV 302
Cdd:cd05850    83 RGTV 86

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.04 E-value: 3.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   40 VIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdKDDPRSHRMLLPSGSLFFLRIVhgrrSKPDEGSYVCVARNYLGEA 119
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPL---KETGRVQIETTASSTSLVIKNA----KRSDSGKYTLTLKNSAGEK 74

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 41.47 E-value: 3.21e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRDQIV---AQGRTVTFPCETKGNPQPAVFWQKEGSqnllfpNQPQQPNSRCSVSpTGDLTITNIQRS-DAGYY 393
Cdd:cd05848     2 PVFVQEPDDAIFptdSDEKKVILNCEARGNPVPTYRWLRNGT------EIDTESDYRYSLI-DGNLIISNPSEVkDSGRY 74

                          90
                  ....*....|....
gi 568997560  394 ICQALTVAGSILAK 407
Cdd:cd05848    75 QCLATNSIGSILSR 88

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.

Pssm-ID: 143290 Cd Length: 95 Bit Score: 41.19 E-value: 3.34e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560  326 DQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNLLFPNQPQQPNSRCSV---SPTG-DLTITNIQRSDAGYYICQALTV 400
Cdd:cd05882     6 DETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYFGEKRALRDNRIQLvksTPTElIISISNVQLSDEGEYTCSIFTM 84

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 41.11 E-value: 3.35e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  440 LLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQDQ-GTLQIKNL---RISD-TGTYTCVATSSSG 499
Cdd:cd05875    20 LIECEAKGNPVPTFHWTRNGKFFnVAKDPRVSMRRRsGTLVIDFRgggRPEDyEGEYQCFARNKFG 85

First immunoglobulin (Ig) domain of contactin-2; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 41.45 E-value: 3.40e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  135 FRQNPTDVVVAAGEP---AILECQPpRGHPEPTIYWKKDKVRID-DKEERISIRGGKLMISNTRKS-DAGMYTCVGTNMV 209
Cdd:cd05850     5 FEEQPSSTLFPEGSAeekVTLACRA-RASPPATYRWKMNGTELKmEPDSRYRLVAGNLVISNPVKAkDAGSYQCLASNRR 83

                          90
                  ....*....|
gi 568997560  210 GERDSDPAEL 219
Cdd:cd05850    84 GTVVSREASL 93

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 40.55 E-value: 3.45e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  240 EAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDIKDDY----TLRIKKAMSTDEGTYVCIAENRVGKVEASATLTVRV 312
Cdd:cd05743     2 ETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggygTLTIRDVKESDQGAYTCEAINTRGMVFGIPDGILTV 78

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 40.89 E-value: 4.30e-04

                          10        20        30
                  ....*....|....*....|....*....|..
gi 568997560   42 VSKGEPTTLNCKAEGRPTPTIEWYKDGERVET 73
Cdd:cd20961     5 VSQGQPVKLNCSVEGMEEPDIQWVKDGAVVQN 36

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.24 E-value: 4.59e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   50 LNCKAEGRPTPTIEWYKDGERVetdKDDPRSHrmLLPSGSLFFLRIvhgrrSKPDEGSYVCVARNYLGEA 119
Cdd:cd05746     3 IPCSAQGDPEPTITWNKDGVQV---TESGKFH--ISPEGYLAIRDV-----GVADQGRYECVARNTIGYA 62

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 41.07 E-value: 4.63e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  419 RPPPIILQGPINQTLAV--DGT--ALLKCKATGEPLPVISWLKEGFTFLGRDPR--ATIQDQGTLQIKNLRIS------D 486
Cdd:cd05773     2 RFAPDLQKGPQLRKVASrgDGSsdANLVCQAQGVPRVQFRWAKNGVPLDLGNPRyeETTEHTGTVHTSILTIInvsaalD 81

                          90       100
                  ....*....|....*....|.
gi 568997560  487 TGTYTCVATSSSGETSWSAVL 507
Cdd:cd05773    82 YALFTCTAHNSLGEDSLDIQL 102

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 40.76 E-value: 4.64e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   37 PSDVIVskGEPTTLNC-KAEGRPTPTIEWYKDGERVETdkdDPRSHRMLlpSGSLFFL-----RIVHGRRSKPDEGSYVC 110
Cdd:cd20950     6 PSSATI--GNRAVLTCsEPDGSPPSEYTWFKDGVVMPT---NPKSTRAF--SNSSYSLdpttgELVFDPLSASDTGEYSC 78

                          90
                  ....*....|....
gi 568997560  111 VARNYLGEAVSRNA 124
Cdd:cd20950    79 EARNGYGTPMRSNA 92

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 40.76 E-value: 5.17e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  332 GRTVTFPCETKGNPQPAVFWQKEGsqnLLFPNQPQQ----PNSRCSVSP-TGDLTITNIQRSDAGYYICQALTVAGS 403
Cdd:cd20950    13 NRAVLTCSEPDGSPPSEYTWFKDG---VVMPTNPKStrafSNSSYSLDPtTGELVFDPLSASDTGEYSCEARNGYGT 86

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 40.73 E-value: 5.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWyKDGERVETDKDDPRSHRMLLPSgslfflrivHGRRSK-------- 102
Cdd:cd05869     3 PKITYVENQTAMELEEQITLTCEASGDPIPSITW-RTSTRNISSEEKTLDGHIVVRS---------HARVSSltlkyiqy 72

                          90       100
                  ....*....|....*....|....*.
gi 568997560  103 PDEGSYVCVARNYLGEAvSRNASLEV 128
Cdd:cd05869    73 TDAGEYLCTASNTIGQD-SQSMYLEV 97

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

Pssm-ID: 409381 Cd Length: 100 Bit Score: 40.84 E-value: 5.52e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  331 QGRTVTFPCE-TKGNPQPAVFWQKEGSQ--NLLFPNQPQQPNSRCSVSPTGD-----LTITNIQRSDAGYYICQA 397
Cdd:cd05716    11 EGGSVTIQCPyPPKYASSRKYWCKWGSEgcQTLVSSEGVVPGGRISLTDDPDngvftVTLNQLRKEDAGWYWCGV 85

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 40.63 E-value: 5.52e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  415 VLTDRPPPIILQgpinqtlavDGTA-LLKCKATGEPLPV-ISWLKEGFTF-LGRDPRATIQDQGTLQIKNLRISDTGTYT 491
Cdd:cd20979     2 VLKEQPAEVLFR---------EGQPtVLECVTEGGDQGVkYSWLKDGKSFnWQEHNVAQRKDEGSLVFLKPQASDEGQYQ 72

                          90
                  ....*....|.
gi 568997560  492 CVATSSSGETS 502
Cdd:cd20979    73 CFAETPAGVAS 83

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 40.69 E-value: 5.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  317 PPqfVVRPRDQIVAQ----GRTVTFPCETKGNPQPAVFWQKEGsqnllfpnQP-QQPNSRCSVSPTG-DLTITNIQRSDA 390
Cdd:cd05730     1 PP--TIRARQSEVNAtanlGQSVTLACDADGFPEPTMTWTKDG--------EPiESGEEKYSFNEDGsEMTILDVDKLDE 70

                          90       100
                  ....*....|....*....|..
gi 568997560  391 GYYICQALTVAGSILAKAQLEV 412
Cdd:cd05730    71 AEYTCIAENKAGEQEAEIHLKV 92

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 40.90 E-value: 6.11e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   426 QGPINQTLAVDGTALLKCKATG---EPLPVISWLK----EGFTFL-----------GRDPRATIQDQ-----GTLQIKNL 482
Cdd:pfam07686    1 QTPREVTVALGGSVTLPCTYSSsmsEASTSVYWYRqppgKGPTFLiayysngseegVKKGRFSGRGDpsngdGSLTIQNL 80

                           90       100
                   ....*....|....*....|....*...
gi 568997560   483 RISDTGTYTCvATSSSGETSWSAVLDVT 510
Cdd:pfam07686   81 TLSDSGTYTC-AVIPSGEGVFGKGTRLT 107

Immunoglobulin variable domain (IgV) Cluster of Differentiation (CD) 79B; The members here are composed of the immunoglobulin variable domain (IgV) of the Cluster of Differentiation (CD) 79B (also known as CD79b molecule, immunoglobulin-associated beta (Ig-beta), and B29). The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. Members of the IgV family are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409515 Cd Length: 96 Bit Score: 40.32 E-value: 6.32e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  318 PQFVVRPRdqivaqGRTVTFPCETKGNPQPAVFWQKeGSQNllfPNQPQQPNSRCSVSPTGD---LTITNIQRSDAGYYI 394
Cdd:cd16096     5 PRFAAKKR------SSMVKFHCYTNYSGVMTWFRKK-GNQR---PQELFPEDGRISQTQNGSvytLTIQNIQYEDNGIYF 74


                  ..
gi 568997560  395 CQ 396
Cdd:cd16096    75 CQ 76

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 39.89 E-value: 6.63e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  428 PINQTLAVDGTAL-LKCKATGEPLPVISWLKEGFTFLGRdpRATIQDQG-TLQIKNLRISDTGTYTCVATSSSG 499
Cdd:cd05876     1 SSSSLVALRGQSLvLECIAEGLPTPTVKWLRPSGPLPPD--RVKYQNHNkTLQLLNVGESDDGEYVCLAENSLG 72

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 40.36 E-value: 7.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  144 VAAGEPAILECQPPRGHPEPTIYWKKDKVRID--DKEERISIRGGK----LMISNTRKSDAGMYTCVGTNMVGErDSDPA 217
Cdd:cd05895    11 VAAGSKLVLRCETSSEYPSLRFKWFKNGKEINrkNKPENIKIQKKKkkseLRINKASLADSGEYMCKVSSKLGN-DSASA 89


                  ....
gi 568997560  218 ELTV 221
Cdd:cd05895    90 NVTI 93

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 40.23 E-value: 7.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  231 PINQVVLEEEAVEFRCQVQGDP--QPTVRWKKD--------DADLPRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd04970     9 PSNADITVGENATLQCHASHDPtlDLTFTWSFNgvpidlekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                          90
                  ....*....|....
gi 568997560  301 KVEASATLTVRVRP 314
Cdd:cd04970    89 SDSASATLVVRGPP 102

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 40.10 E-value: 8.00e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568997560  144 VAAGEPAILECQPpRGHPEPTIYWKKDKVRID----DKEERISIRGGK--LMISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd20951    12 VWEKSDAKLRVEV-QGKPDPEVKWYKNGVPIDpssiPGKYKIESEYGVhvLHIRRVTVEDSAVYSAVAKNIHGE 84

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

Pssm-ID: 409538 Cd Length: 102 Bit Score: 40.21 E-value: 8.54e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  142 VVVAAGEPAILECQPPRGHPEPTIYWKKDKVRID-----------DKEERISIRGGKLMISNTRKSDAGMYTCvgtnMVG 210
Cdd:cd20946     9 VTVVENQEVILSCKTPKKTSSPRVEWKKLQRDVTfvvfqnnkiqgDYKGRAEILGTNITIKNVTRSDSGKYRC----EVS 84

                          90
                  ....*....|....*..
gi 568997560  211 ER------DSDPAELTV 221
Cdd:cd20946    85 ARsdgqnlGEVTVTLEV 101

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 39.99 E-value: 8.58e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568997560  144 VAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERIS----------IRGGKLMISNTRKSDAGMYTCVGTNMVG 210
Cdd:cd20950     9 ATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRafsnssysldPTTGELVFDPLSASDTGEYSCEARNGYG 85

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 39.83 E-value: 1.02e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997560  246 CQVQGDPQPTVRWKKDDADLPRGRYDIKDDY------TLRIKKAMSTDEGTYVCIAENRVGKVEASATLTV 310
Cdd:cd20953    25 CPAQGYPAPSFRWYKFIEGTTRKQAVVLNDRvkqvsgTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLTV 95

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 39.96 E-value: 1.04e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568997560  441 LKCKATGEPLPVISW-------LKEGFTFLGRDPRATIQDQGTLQIKNLRISDTGTYTCVATSSSGETSWSAVLDV 509
Cdd:cd05869    22 LTCEASGDPIPSITWrtstrniSSEEKTLDGHIVVRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 39.91 E-value: 1.12e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHP-SDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVetdKDDPRSHRMLLPSGSLFFlrivhgRRSKPDE-GSY 108
Cdd:cd05760     1 PVVLKHPaSAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPL---SDGQGNYSVSSKERTLTL------RSAGPDDsGLY 71

                          90       100
                  ....*....|....*....|..
gi 568997560  109 VCVARNYLGEAVS-RNASLEVA 129
Cdd:cd05760    72 YCCAHNAFGSVCSsQNFTLSII 93

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

Pssm-ID: 409504 Cd Length: 86 Bit Score: 39.35 E-value: 1.20e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  242 VEFRCQVQGDPQPTVRWKKDDADlprGRYDIK--DDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLtvrvrpvappQ 319
Cdd:cd16082    16 ISLQCQAWGSPPISYVWYKEQTN---NQEPIKvaALSTLLFKPAVVADSGSYFCTAKGRVGSEQRSDIV----------K 82


                  ....
gi 568997560  320 FVVR 323
Cdd:cd16082    83 FVVK 86

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 39.84 E-value: 1.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   30 PPRIVEHPSDVIVSKGEPTTLNCKAEGRPTP--TIEWYKDGERVETDKDDPRSHR--MLLPSGSLFflrIVHGRRSkpDE 105
Cdd:cd04970     2 ATRITLAPSNADITVGENATLQCHASHDPTLdlTFTWSFNGVPIDLEKIEGHYRRryGKDSNGDLE---IVNAQLK--HA 76

                          90       100
                  ....*....|....*....|....
gi 568997560  106 GSYVCVARNYLgEAVSRNASLEVA 129
Cdd:cd04970    77 GRYTCTAQTVV-DSDSASATLVVR 99

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 40.01 E-value: 1.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  426 QGPINQTLAVDGTALLKCKATGE-PLPVISWLK----EGFTFL------------GRDPRATI----QDQGTLQIKNLRI 484
Cdd:cd00099     3 QSPRSLSVQEGESVTLSCEVSSSfSSTYIYWYRqkpgQGPEFLiylssskgktkgGVPGRFSGsrdgTSSFSLTISNLQP 82

                          90
                  ....*....|....*
gi 568997560  485 SDTGTYTCVATSSSG 499
Cdd:cd00099    83 EDSGTYYCAVSESGG 97

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 39.84 E-value: 1.22e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568997560   42 VSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDkddprsHRMllpSGSLFFLR---IVHGRRSKPDEGSYVCVARNYLG 117
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQE------HRI---GGYKVRNQhwsLIMESVVPSDKGNYTCVVENEYG 85

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 39.38 E-value: 1.31e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRMLlpsGSLFFlrIVHGRRSKPDEGSYVC 110
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFK---GGYHQ--LIIASVTDDDATVYQV 76


                  ....*....
gi 568997560  111 VARNYLGEA 119
Cdd:cd20971    77 RATNQGGSV 85

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 39.36 E-value: 1.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  143 VVAAGEPAILEC-QPPRGHPEPTIYWKKDKVRIDDKEERISIRGGkLMISNTRKSDAGMYTCVGTNMVGERDSDPAELTV 221
Cdd:cd04979     7 SVKEGDTVILSCsVKSNNAPVTWIHNGKKVPRYRSPRLVLKTERG-LLIRSAQEADAGVYECHSGERVLGSTLRSVTLHV 85


                  ...
gi 568997560  222 FER 224
Cdd:cd04979    86 LER 88

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 39.35 E-value: 1.34e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  329 VAQGRTVTFPCETKGNPQPAVFWQKEGS--QNLlfpNQPQQPNSRCSVspTGDLTITNIQRSDAGYYICQ 396
Cdd:cd20961     5 VSQGQPVKLNCSVEGMEEPDIQWVKDGAvvQNL---DQLYIPVSEQHW--IGFLSLKSVERSDAGRYWCQ 69

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.42 E-value: 1.40e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   42 VSKGEPTTLNCKAEGR-PTPTIEWYKDGERVETDKDD-------PRSHRmllpsgslffLRIvhGRRSKPDEGSYVCVAR 113
Cdd:cd05750    11 VQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRPKnikirnkKKNSE----------LQI--NKAKLEDSGEYTCVVE 78


                  ....*....
gi 568997560  114 NYLGEAVSR 122
Cdd:cd05750    79 NILGKDTVT 87

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 39.60 E-value: 1.41e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  420 PPPIILQgPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGR------DPRATIQDQGTLQIKNLRISDTGTYTCV 493
Cdd:cd20954     1 PPRWIVE-PVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEykdllyDPNVRILPNGTLVFGHVQKENEGHYLCE 79


                  ....*.
gi 568997560  494 ATSSSG 499
Cdd:cd20954    80 AKNGIG 85

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.40 E-value: 1.46e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  147 GEPAILECQPpRGHPEPTIYWKKDKVR-------IDDKEERISIRG-GKLMISNTRKSDAGMYTCVGTNMVGERDSDPAE 218
Cdd:cd05734    16 GKAVVLNCSA-DGYPPPTIVWKHSKGSgvpqfqhIVPLNGRIQLLSnGSLLIKHVLEEDSGYYLCKVSNDVGADISKSMY 94


                  ...
gi 568997560  219 LTV 221
Cdd:cd05734    95 LTV 97

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 39.37 E-value: 1.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRDPRATI-QDQG---TLQIKNLRISDTGTYTCVATSS 497
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLyQDNCgriCLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|..
gi 568997560  498 SGETSWSAVLDV 509
Cdd:cd05892    81 AGVVSCNARLDV 92

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 39.26 E-value: 1.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   38 SDVIVSKGEPTTLNCKAEGRPTPTIEWYKDGE--------RVETDKDDPRShRMLLPSGslfflrivhgrrSKPDEGSYV 109
Cdd:cd20974     8 QSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQviststlpGVQISFSDGRA-KLSIPAV------------TKANSGRYS 74

                          90
                  ....*....|..
gi 568997560  110 CVARNYLGEAVS 121
Cdd:cd20974    75 LTATNGSGQATS 86

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 38.93 E-value: 2.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  225 PTFLRRPINQVVLEEE-AVEFRCQVQGDPQPTVRWKKDD----ADLPrGRYDIKDDYTLRIKKAMSTD------EGTYVC 293
Cdd:cd20955     2 PVFLKEPTNRIDFSNStGAEIECKASGNPMPEIIWIRSDgtavGDVP-GLRQISSDGKLVFPPFRAEDyrqevhAQVYAC 80


                  ....*....
gi 568997560  294 IAENRVGKV 302
Cdd:cd20955    81 LARNQFGSI 89

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 38.72 E-value: 2.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  416 LTDRPPPIILQGPINQTLAVDGTAL-LKCKATgEPLPVISWLKEGFTfLGRDPRATIQDQgTLQIKNLRISDTGTYTCVA 494
Cdd:cd04973     3 LPPEAPPTYQISEVESYSAHPGDLLqLRCRLR-DDVQSINWTKDGVQ-LGENNRTRITGE-EVQIKDAVPRDSGLYACVT 79

                          90
                  ....*....|....*
gi 568997560  495 TSSSGETSWSAVLDV 509
Cdd:cd04973    80 SSPSGSDTTYFSVNV 94

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 38.54 E-value: 2.61e-03

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 568997560  317 PPQFVVRPRDQIVAQgrtvtfpCETKGNPQPAVFWQKEG 355
Cdd:cd05733     8 PKDYIVDPRDNITIK-------CEAKGNPQPTFRWTKDG 39

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 39.18 E-value: 2.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  227 FLRRPINQVVLEEEAVEFRCQVQGDPQPTVRW-------------KKDDADLPR----GRYDIKDDYTLRIKKAMSTDEG 289
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWwfegqepneicsqLWDGARLDRvhinATYHQHATSTISIDNLTEEDTG 82


                  ....*...
gi 568997560  290 TYVCIAEN 297
Cdd:cd20940    83 TYECRASN 90

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 38.81 E-value: 2.77e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTF-LGRDPRATIQ-DQGTLQIKNLRISDT----GTYTCVA 494
Cdd:cd05874     1 PTITHQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFdIDKDPKVTMKpNTGTLVINIMNGEKAeayeGVYQCTA 80


                  ....*
gi 568997560  495 TSSSG 499
Cdd:cd05874    81 RNERG 85

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 38.66 E-value: 2.83e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560   43 SKGEPTTLNCKAEGRPTPTIEWYKDGERVETDKDDPRSHRMLLPSGSLFFLRIVHGRRSkpDEGSYVCVARNYLG 117
Cdd:cd05732    14 VELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLDGRIVVRGHARVSSLTLKDVQLT--DAGRYDCEASNRIG 86

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

Pssm-ID: 409455 Cd Length: 92 Bit Score: 38.48 E-value: 2.94e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  142 VVVAAGEPAILECQPPRghPEPTIYWKKDKVRIDDK-----EERISIRGGKLMISNTRKSDAGMYTCVGT 206
Cdd:cd05871     7 VYGVEGNSTFLECLPKS--PQATVKWLFQRGGDQRKeevksEERLIVTDRGLLLRSLQRSDAGVYTCQAV 74

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 38.54 E-value: 3.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  422 PIILQGPINQTLAVDGT-ALLKCKATGEPLPVISWLKEGFTFLGRDP-RATIQDQGTLQIKNLRISD------TGTYTCV 493
Cdd:cd20955     2 PVFLKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDGTAVGDVPgLRQISSDGKLVFPPFRAEDyrqevhAQVYACL 81


                  ....*.
gi 568997560  494 ATSSSG 499
Cdd:cd20955    82 ARNQFG 87

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 38.06 E-value: 3.38e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   40 VIVSKGEPTTLNCKAEGRPTPTIEWYKDGERVETDkddprSHRMLLPSGSLFFLRIvhgrrSKPDEGSYVCVARNYLGEA 119
Cdd:cd05852    12 ILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNN-----SRISIWDDGSLEILNI-----TKLDEGSYTCFAENNRGKA 81


                  ....*....
gi 568997560  120 VSrNASLEV 128
Cdd:cd05852    82 NS-TGVLSV 89

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 38.35 E-value: 3.48e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  228 LRRPINQVVLEEEAVEFRCQVQGDPQPTVRWKKDDADLPRgRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASAT 307
Cdd:cd04976     7 RKQQVLEATAGKRSVRLPMKVKAYPPPEVVWYKDGLPLTE-KARYLTRHSLIIKEVTEEDTGNYTILLSNKQSNVFKNLT 85


                  ....*
gi 568997560  308 LTVRV 312
Cdd:cd04976    86 ATLVV 90

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 38.54 E-value: 3.53e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVI-VSKGEPTTLNCKAEGRPTPTIEWYK-DGERVetdkDDPRSHRMLLPSGSLFFLRI-VHGRRSKPDEGS 107
Cdd:cd20955     2 PVFLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWIRsDGTAV----GDVPGLRQISSDGKLVFPPFrAEDYRQEVHAQV 77

                          90
                  ....*....|....*.
gi 568997560  108 YVCVARNYLGEAVSRN 123
Cdd:cd20955    78 YACLARNQFGSIISRD 93

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 38.30 E-value: 3.60e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   31 PRIVEHPSDVIVSKGEPTTLNCKAEGRPTPTIEWYK---DGERVETDKDDPRSHRMLLPSGSLfflrIVHGRRSKpDEGS 107
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvpGKENLIMRPNHVRGNVVVTNIGQL----VIYNAQPQ-DAGL 75

                          90
                  ....*....|
gi 568997560  108 YVCVARNYLG 117
Cdd:cd05765    76 YTCTARNSGG 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 38.30 E-value: 3.77e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   45 GEPTTLNCKAEGRPTPTIEWYKDGER-VETDKDDPRSHRMLLPSGSLfflrivhgrrsKP-DEGSYVCVARNYLGEAvsr 122
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPlTPPEIGENKKKKWTLSLKNL-----------KPeDSGKYTCHVSNRAGEI--- 84


                  ....*.
gi 568997560  123 NASLEV 128
Cdd:cd05856    85 NATYKV 90

Chitodextrinase [Carbohydrate transport and metabolism];

Pssm-ID: 443178 [Multi-domain] Cd Length: 369 Bit Score: 41.30 E-value: 3.79e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  526 PGPPSKPQVTDVSKNSVTLSWQPGTPGVLPASAYiieafsqsVSNSWQTVANHVKTTLYTVRGLRPNTIYLFMVRAINPQ 605
Cdd:COG3979     3 PTAPTGLTASNVTSSSVSLSWDASTDNVGVTGYD--------VYRGGDQVATVTGLTAWTVTGLTPGTEYTFTVGACDAA 74

                          90
                  ....*....|..
gi 568997560  606 G-LSDPSPMSDP 616
Cdd:COG3979    75 GnVSAASGTSTA 86

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 38.31 E-value: 3.93e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  158 RGHPEPTIYWKKDKVRIDDkEERISI-----RGGKLM----ISNTRKSDAGMYTCVGTNMVGE 211
Cdd:cd20956    26 SGNPLPQITWTLDGFPIPE-SPRFRVgdyvtSDGDVVsyvnISSVRVEDGGEYTCTATNDVGS 87

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 38.04 E-value: 4.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  316 APPQFVVRPRDQIVAQgrtvtfpCETKGNPQPAVFWQKEGSQnllF-----PNQPQQPNSRCSVsptgdLTITNIQRSDA 390
Cdd:cd05874     7 SPKDYIVDPRENIVIQ-------CEAKGKPPPSFSWTRNGTH---FdidkdPKVTMKPNTGTLV-----INIMNGEKAEA 71

                          90
                  ....*....|....*...
gi 568997560  391 --GYYICQALTVAGSILA 406
Cdd:cd05874    72 yeGVYQCTARNERGAAVS 89

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409449 Cd Length: 88 Bit Score: 37.99 E-value: 4.32e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  425 LQGPINQTLAVDGTALLKCKATGEPLPVISWLKEGFTFLGRdpratiQDQGTLQIKNLRISDTGTYTCVATSS 497
Cdd:cd05863     8 RKGPVIEATAGDELVKLPVKVAAYPPPEFQWYKDGKLISGK------HSPHSLQIKDVTEASAGTYTLVLWNS 74

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 37.57 E-value: 4.38e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568997560  342 KGNPQPAVFWQKEGsQNLLFPNQPQQPNSRCSVSptgdLTITNIQRSDAGYYICQALTVAGSilAKAQLEV 412
Cdd:cd05748    17 KGRPTPTVTWSKDG-QPLKETGRVQIETTASSTS----LVIKNAKRSDSGKYTLTLKNSAGE--KSATINV 80

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 38.00 E-value: 4.68e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  428 PINQTLAVDGTALLKCKATGEPlPVISWLK-EGFTFLGRDPRATIQDQG----TLQIKNLRISDTGTYTCVATSSSGETS 502
Cdd:cd04977     7 PSYAEISVGESKFFLCKVSGDA-KNINWVSpNGEKVLTKHGNLKVVNHGsvlsSLTIYNANINDAGIYKCVATNGKGTES 85


                  ....
gi 568997560  503 WSAV 506
Cdd:cd04977    86 EATV 89

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409363 Cd Length: 102 Bit Score: 38.17 E-value: 4.88e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKGNPQPAVFWQKEGSQNllfpNQPQQPNS--------RCSVSPTGD---LTITNIQRSDAGY 392
Cdd:cd04974     8 PANQTVVLGSDVEFHCKVYSDAQPHIQWLKHVEVN----GSKYGPDGlpyvtvlkVAGVNTTGEentLTISNVTFDDAGE 83

                          90
                  ....*....|....*.
gi 568997560  393 YICQAltvAGSILAKA 408
Cdd:cd04974    84 YICLA---GNSIGLSF 96

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 41.53 E-value: 5.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  504 SAVLDVTESGATISKNYDMNDLPGPPSKPQVTdvsknSVTLSWQPGTPGVLPASAYIIEAFSQSVSNSWQTVANHVKTTL 583
Cdd:COG3401     8 SLDAGIAASAAANTAVNALSKAGGSGKTILVY-----LAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  584 YTVRGLRPNTIYLFMVRAINPQGLSDPSPMSDPVRTQDISPPAQGVDHRQVQKELGDVVVRLHNPVVLTPTTVQVTWTVd 663
Cdd:COG3401    83 AVAAAPPTATGLTTLTGSGSVGGATNTGLTSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTAS- 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  664 rqpqfIQGYRVMYRQTSGLQASTVWQNLDAKVPTERSAVLVNLKKGVTYEIKVRPYFNEFQGMDSESKTVRTTEEAPSAP 743
Cdd:COG3401   162 -----SVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAP 236

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 568997560  744 pqsvTVLTVGSHNSTSISVSWDPPPADHqngiIQEYKI 781
Cdd:COG3401   237 ----TGLTATADTPGSVTLSWDPVTESD----ATGYRV 266

Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain; The members here are composed of the immunoglobulin (Ig)-like variable domain of the Cluster of Differentiation (CD) 8 alpha. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. The Ig domain of CD8 alpha binds to antibodies. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409385 Cd Length: 110 Bit Score: 38.23 E-value: 5.38e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  320 FVVRPRDQIVAQGRTVTFPCETKGNPQPAVFW--QKEGSQN----LLFPNQPQQP-------NSRCSVSPTGD---LTIT 383
Cdd:cd05720     1 FRMSPRKRDAQLGQKVELVCEVLNSVPQGCSWlfQPRGSAPqptfLLYLSSSNKTkwaegldSKRFSGSRSGSsyvLTLK 80

                          90
                  ....*....|....*
gi 568997560  384 NIQRSDAGYYICQAL 398
Cdd:cd05720    81 DFRKEDEGYYFCSVI 95

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

Pssm-ID: 409372 [Multi-domain] Cd Length: 109 Bit Score: 38.02 E-value: 5.44e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  324 PRDQIVAQGRTVTFPCETKGNPQPAVFWQK----EGSQNLL--FPNQPQQPNSRCSVSPTGD-----LTITNIQRSDAGY 392
Cdd:cd04983     5 PQSLSVQEGENVTLNCNYSTSTFYYLFWYRqypgQGPQFLIyiSSDSGNKKKGRFSATLDKSrksssLHISAAQLSDSAV 84

                          90
                  ....*....|.
gi 568997560  393 YICqALTVAGS 403
Cdd:cd04983    85 YFC-ALSESGG 94

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409407 Cd Length: 82 Bit Score: 37.06 E-value: 6.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560   35 EHPSDVIVSKGEPTTLNCKAEGRPTP-TIEWYKDGERVETDKDdprshrmllPSGSLFFLRIVHgRRSKpdegsYVCVAR 113
Cdd:cd05749     4 VEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSPLGGPPA---------PSPSVLNVPGLN-ETTK-----FSCEAH 68

                          90
                  ....*....|....
gi 568997560  114 NYLGEAVSRNASLE 127
Cdd:cd05749    69 NAKGLTSSRTATVT 82

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 1 (VEGFR-1). VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-1 binds VEGF-A strongly; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-1 may play an inhibitory role in the function of VEGFR-2 by binding VEGF-A and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis and may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409499 Cd Length: 92 Bit Score: 37.16 E-value: 7.52e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568997560  158 RGHPEPTIYWKKDKVRIDDKEERISIRGGKLMISNTRKSDAGMYTCV 204
Cdd:cd07702    28 KAFPSPEVIWLKDGLPATEKCARYLTRGYSLIIKDVTEEDAGNYTIL 74

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 37.37 E-value: 7.62e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568997560  334 TVTFPCETKgNPQPAVFWqkegsqnlLFPNQPQQPNSRCSVSPTG-DLTITNIQRSDAGYYICQA 397
Cdd:cd05740    17 AVTLTCEPE-TQNTSYLW--------WFNGQSLPVTPRLTLSNGNrTLTLLNVTREDAGAYQCEI 72

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 37.47 E-value: 7.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  421 PPIILQGPiNQTLAVDGTAL-LKCKATGEPLPVISWLKEGFTF-LGRDPR--ATIQDQG-----TLQIKNLRISDTGTYT 491
Cdd:cd05735     3 PAMITSYP-NTTLATKGQKKeMSCTAHGEKPIIVRWEKEDTIInPSEMSRylVTTKEVGdevisTLQILPTVREDSGFFS 81


                  ....*....
gi 568997560  492 CVATSSSGE 500
Cdd:cd05735    82 CHAINSYGE 90

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 36.81 E-value: 8.06e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  328 IVAQGRTVTFPCETKGNPQPAVFWQKegsqnllfPNQPQQPNSRCSVSPTGDLTITNIQRSDAGYYICQALTVAGSilAK 407
Cdd:cd05876     6 VALRGQSLVLECIAEGLPTPTVKWLR--------PSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS--AR 75


                  ....*.
gi 568997560  408 AQLEVT 413
Cdd:cd05876    76 HAYYVT 81

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 37.21 E-value: 8.08e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568997560  250 GDPQPTVRWKKDDADLpRGRYDIKDDYTLRIKKAMSTDEGTYVCIAENRVGKVEASATLTVRV 312
Cdd:cd05864    28 GYPPPEIKWYKNGIPI-ESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEKQRHTFSLVV 89

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 37.08 E-value: 9.92e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568997560  231 PINQVVLEEEAVEFRCQVQGDPQPTVRWKKDD-----ADLPRGRYDIKDD-----YTLRIKKAMSTDEGTYVCIAENRVG 300
Cdd:cd05735    10 PNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDtiinpSEMSRYLVTTKEVgdeviSTLQILPTVREDSGFFSCHAINSYG 89

                          90
                  ....*....|.
gi 568997560  301 KVEASATLTVR 311
Cdd:cd05735    90 EDRGIIQLTVQ 100