NCBI Conserved Domain Search

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. 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 different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

Pssm-ID: 409439 Cd Length: 102 Bit Score: 221.81 E-value: 7.50e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  496 DPTKVMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFTWTFNGHLIDFDKDGDHFERVGG-DSAGDLMIRNIQLKHAGKYV 574
Cdd:cd05853      1 DPTRVMVPPSSMDVTVGESIVLPCQVSHDHSLDIVFTWSFNGHLIDFQKDGDHFERVGGqDSAGDLMIRSIQLKHAGKYV 80

                           90       100
                   ....*....|....*....|..
gi 1958767848  575 CMVQTSVDKLSAAADLIVRGPP 596
Cdd:cd05853     81 CMVQTSVDKLSAAADLIVRGPP 102

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: 183.52 E-value: 2.81e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  496 DPTKVMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFTWTFNGHLIDFDKDGDHFERVGG-DSAGDLMIRNIQLKHAGKYV 574
Cdd:cd04970      1 DATRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVPIDLEKIEGHYRRRYGkDSNGDLEIVNAQLKHAGRYT 80

                           90       100
                   ....*....|....*....|..
gi 1958767848  575 CMVQTSVDKLSAAADLIVRGPP 596
Cdd:cd04970     81 CTAQTVVDSDSASATLVVRGPP 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: 158.48 E-value: 1.30e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKArRHKSSGILEIPNFQQEDAGSYECVAENSRGKN 304
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWE-ITTSEPVLEIPNVQFEDEGTYECEAENSRGKD 79


                   ....*....
gi 1958767848  305 IAKGQVTFY 313
Cdd:cd04968     80 TVQGRIIVQ 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: 157.03 E-value: 5.69e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   25 GPVFVQEPSHVMFPLDSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATN 104
Cdd:cd05848      1 GPVFVQEPDDAIFPTDSDEKKVILNCEARGNPVPTYRWLRNGTEIDTESDYRYSLIDGNLIISNPSEVKDSGRYQCLATN 80

                           90
                   ....*....|....*.
gi 1958767848  105 SFGTIVSREAKLQFAY 120
Cdd:cd05848     81 SIGSILSREALLQFAY 96

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: 150.09 E-value: 1.73e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   25 GPVFVQEPSHVMFPLDSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATN 104
Cdd:cd04967      1 GPVFEEQPDDTIFPEDSDEKKVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLVDGTLVISNPSKAKDAGHYQCLATN 80

                           90
                   ....*....|....*.
gi 1958767848  105 SFGTIVSREAKLQFAY 120
Cdd:cd04967     81 TVGSVLSREATLQFGY 96

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: 141.44 E-value: 1.17e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGT 485
Cdd:cd04969      1 PDFELNPVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80


                   ....*....
gi 1958767848  486 ASSTGNVVV 494
Cdd:cd04969     81 ANSTGSLSV 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: 138.89 E-value: 8.15e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  318 WVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASA 397
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ....
gi 1958767848  398 ELSV 401
Cdd:cd05728     82 ELAV 85

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: 129.01 E-value: 4.33e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  496 DPTKVMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFTWTFNGHLIDFDKDGDHFERVGG-DSAGDLMIRNIQLKHAGKYV 574
Cdd:cd05854      1 DATKITLAPSSADINQGENLTLQCHASHDPTMDLTFTWSLDDFPIDLDKPNGHYRRMEVkETIGDLVIVNAQLSHAGTYT 80

                           90       100
                   ....*....|....*....|..
gi 1958767848  575 CMVQTSVDKLSAAADLIVRGPP 596
Cdd:cd05854     81 CTAQTVVDSASASATLVVRGPP 102

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: 125.42 E-value: 5.83e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   24 HGPVFVQEPSHVMFPLDSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIAT 103
Cdd:cd05850      1 YGPVFEEQPSSTLFPEGSAEEKVTLACRARASPPATYRWKMNGTELKMEPDSRYRLVAGNLVISNPVKAKDAGSYQCLAS 80

                           90
                   ....*....|....*..
gi 1958767848  104 NSFGTIVSREAKLQFAY 120
Cdd:cd05850     81 NRRGTVVSREASLRFGF 97

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: 112.36 E-value: 2.61e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   25 GPVFVQEPSHVMFPLDSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDfRYSVVEGSLLINNPNKTQDSGTYQCIATN 104
Cdd:cd05849      1 GPVFEEQPIDTIYPEESTEGKVSVNCRARANPFPIYKWRKNNLDIDLTND-RYSMVGGNLVINNPDKYKDAGRYVCIVSN 79

                           90
                   ....*....|....*.
gi 1958767848  105 SFGTIVSREAKLQFAY 120
Cdd:cd05849     80 IYGKVRSREATLSFGY 95

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: 104.31 E-value: 1.54e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGT 485
Cdd:cd05852      1 PTFEFNPMKKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGK 80


                   ....*....
gi 1958767848  486 ASSTGNVVV 494
Cdd:cd05852     81 ANSTGVLSV 89

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second 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: 409392 Cd Length: 88 Bit Score: 102.65 E-value: 4.93e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  129 RSTVSVRRGQGMVLLCGPPPHSGELSYAWIFNEHPSY--QDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNTVTSHQVL 206
Cdd:cd05727      2 RDEVKVKEGWGVVLFCDPPPHYPDLSYRWLLNEFPNFipEDGRRFVSQTNGNLYIAKVEASDRGNYSCFVSSPSSTKSVF 81


                   ....*..
gi 1958767848  207 GPPTPLI 213
Cdd:cd05727     82 SKFIPLR 88

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: 85.46 E-value: 4.61e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVpAEKGSTVKLECFALGNPVPTILWRRADgKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGKN 304
Cdd:cd05851      2 ADINVKFKDTY-ALKGQNVTLECFALGNPVPVIRWRKIL-EPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKD 79

                           90
                   ....*....|.
gi 1958767848  305 iaKGQVTFYAQ 315
Cdd:cd05851     80 --KHQARVYVQ 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: 82.82 E-value: 4.63e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFPLDSEEkkVKLSCEVKGNPKPHIRWKLNGTDVDiGMDFRYSVVEGSLLINNPNKtQDSGTYQCIATNS 105
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQD--VTLPCQVTGVPQPKITWLHNGKPLQ-GPMERATVEDGTLTIINVQP-EDTGYYGCVATNE 76

                           90
                   ....*....|..
gi 1958767848  106 FGTIVSrEAKLQ 117
Cdd:cd20978     77 IGDIYT-ETLLH 87

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: 80.62 E-value: 3.48e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  596 PGPPEAVTIDEITDTTAQLSWRPGPDNHSPITMYVIQARTPFSVGWQAVSTVPelvdGKTFTATVVGLNPWVEYEFRTVA 675
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTP----GSETSYTLTGLKPGTEYEFRVRA 76

                           90
                   ....*....|....
gi 1958767848  676 ANVIGIGEPSRPSE 689
Cdd:cd00063     77 VNGGGESPPSESVT 90

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: 78.97 E-value: 9.83e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLLKRVTlVKVGGEVVIECKPKASPRPVYTW-RKGREILRENERITIsEDGNLRIINVTKSDAGSYTCIATNHFG 484
Cdd:cd20978      1 PKFIQKPEKNVV-VKGGQDVTLPCQVTGVPQPKITWlHNGKPLQGPMERATV-EDGTLTIINVQPEDTGYYGCVATNEIG 78

                           90
                   ....*....|
gi 1958767848  485 TASSTGNVVV 494
Cdd:cd20978     79 DIYTETLLHV 88

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: 78.70 E-value: 1.22e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   415 RVTLVKVGGEVVIECKPKASPRPVYTWRK-GREILRENERITISEDGN---LRIINVTKSDAGSYTCIATNHFGTASSTG 490
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1958767848   491 NVVV 494
Cdd:smart00410   82 TLTV 85

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: 78.67 E-value: 1.50e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   28 FVQEPSHVmfpLDSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVV-EGSLLINNPNKTQ----DSGTYQCIA 102
Cdd:cd05722      4 FLSEPSDI---VAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLpNGSLLITSVVHSKhnkpDEGFYQCVA 80

                           90
                   ....*....|....*.
gi 1958767848  103 TN-SFGTIVSREAKLQ 117
Cdd:cd05722     81 QNeSLGSIVSRTARVT 96

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 76.91 E-value: 5.27e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSrTLLKRVTlVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGN---LRIINVTKSDAGSYTCIATNH 482
Cdd:pfam07679    1 PKFT-QKPKDVE-VQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGtytLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1958767848  483 FGTASSTGNVVV 494
Cdd:pfam07679   79 AGEAEASAELTV 90

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: 76.77 E-value: 6.11e-17

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRK-GREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd20952      9 QTVAVGGTVVLNCQATGEPVPTISWLKdGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 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: 74.36 E-value: 3.63e-16

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  417 TLVKVGGEVVIECK-PKASPRPVYTWRK-GREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd05724      7 TQVAVGEMAVLECSpPRGHPEPTVSWRKdGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80

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: 73.97 E-value: 6.29e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQ-IINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLL-TRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVI 393
Cdd:cd20978      1 PKFIQkPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDI 80


                   ....*...
gi 1958767848  394 YASAELSV 401
Cdd:cd20978     81 YTETLLHV 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: 73.82 E-value: 7.01e-16

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd20968     14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 72.45 E-value: 1.52e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  597 GPPEAVTIDEITDTTAQLSWRPGPDNHSPITMYVIQARTPFSVGWQAVSTVPelvdGKTFTATVVGLNPWVEYEFRTVAA 676
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVP----GTTTSVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 1958767848  677 NVIGIGEPS 685
Cdd:pfam00041   77 NGGGEGPPS 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: 72.43 E-value: 1.56e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADGK-PIARKARRHKSSgiLEIPNFQQEDAGSYECVAENSRGKNIAKGQV 310
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGElPKGRYEILDDHS--LKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                   .
gi 1958767848  311 T 311
Cdd:cd05725     82 T 82

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 1.62e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  768 PFSPFEVKVGVFNNKGEGPFSPTTLVYSAEEEPTkPPASIFARSLSATDIEVFWASPIGKnrgRIQGYEVKywRHDDKEE 847
Cdd:COG3401    201 PGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVTES---DATGYRVY--RSNSGDG 274

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  848 NARKIRTVgNQTSTKITNLKGNALYHLSVKAYNSAGT-GPSSAAVNVTTRKPPPSQPPGNIIWNSSDSKIILNWDQVKAL 926
Cdd:COG3401    275 PFTKVATV-TTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASSDA 353

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  927 DneseVKGYKVlYRWNRQSS--TSVIETNKTS--VELSLPFDEDYIIEIKPFSDGGDGS-SSEQIRIPKISNSYARGSGA 1001
Cdd:COG3401    354 D----VTGYNV-YRSTSGGGtyTKIAETVTTTsyTDTGLTPGTTYYYKVTAVDAAGNESaPSEEVSATTASAASGESLTA 428

                          250
                   ....*....|..
gi 1958767848 1002 STSNACTLSAIS 1013
Cdd:COG3401    429 SVDAVPLTDVAG 440

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: 71.77 E-value: 3.50e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   232 PETVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKAR----RHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....
gi 1958767848   308 GQVT 311
Cdd:smart00410   81 TTLT 84

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: 71.67 E-value: 4.17e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEP--SHVMFPLDSeekkVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVE--GSLLINNPNK--TQDSGTYQ 99
Cdd:cd05733      1 PTITEQSpkDYIVDPRDN----ITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRrsGTLVIDNHNGgpEDYQGEYQ 76

                           90
                   ....*....|....*...
gi 1958767848  100 CIATNSFGTIVSREAKLQ 117
Cdd:cd05733     77 CYASNELGTAISNEIRLV 94

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: 71.37 E-value: 5.14e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  227 IEVQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHKS--SGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd20952      1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLK-DGVPLLGKDERITTleNGSLQIKGAEKSDTGEYTCVALNLSGE 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.67 E-value: 7.04e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  225 PKIEVQfPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIA----RKARRHKSSGILEIPNFQQEDAGSYECVAEN 299
Cdd:pfam13927    2 PVITVS-PSSVTVREGETVTLTCEATGSPPPTITWYK-NGEPISsgstRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.82 E-value: 3.92e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQ----GTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYeggtYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1958767848  392 VIYASAELSV 401
Cdd:pfam07679   81 EAEASAELTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.82 E-value: 4.24e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFpldSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEG--SLLINNPNKtQDSGTYQCIAT 103
Cdd:pfam07679    1 PKFTQKPKDVEV---QEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGtyTLTISNVQP-DDSGKYTCVAT 76

                           90
                   ....*....|....
gi 1958767848  104 NSFGTiVSREAKLQ 117
Cdd:pfam07679   77 NSAGE-AEASAELT 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: 68.69 E-value: 4.33e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   324 DIHVAMEESVFWECKANGRPKPTYRWLKNG-DPLLTRERIQIE----QGTLNITIVNLSDAGMYQCVAENKHGVIYASAE 398
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSrsgsTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 1958767848   399 LSV 401
Cdd:smart00410   83 LTV 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: 67.74 E-value: 5.39e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVE--GSLLINNPNKtQDSGTYQCIATNSFGTIVSREA 114
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELgnGTLTISNVTL-EDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 67.21 E-value: 9.70e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  411 TLLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGN---LRIINVTKSDAGSYTCIATN 481
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSnstLTISNVTRSDAGTYTCVASN 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: 66.58 E-value: 1.44e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  425 VVIECKPKASPRPVYTWRKGREILREN---ERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSsrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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: 65.98 E-value: 4.33e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  803 PPASIFARSLSATDIEVFWASPIGKNrGRIQGYEVKYWRHDdkEENARKIRT-VGNQTSTKITNLKGNALYHLSVKAYNS 881
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDDG-GPITGYVVEYREKG--SGDWKEVEVtPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|....
gi 1958767848  882 AGTGPSSAAVNVTT 895
Cdd:cd00063     80 GGESPPSESVTVTT 93

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: 64.66 E-value: 6.13e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  336 ECKANGRPKPTYRWLKNGDPLLT----RERIQIEQGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd00096      4 TCSASGNPPPTITWYKNGKPLPPssrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

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: 64.02 E-value: 1.86e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  320 QIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVIYASAE 398
Cdd:cd04969      7 PVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICIlPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGS 86


                   ...
gi 1958767848  399 LSV 401
Cdd:cd04969     87 LSV 89

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: 64.11 E-value: 1.92e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFPLDSeekKVKLSCEVKGNPKPHIRWKLNG----TDVDIGMDFRYSVVEGSL----LINNPNKTQDSGT 97
Cdd:cd07693      1 PRIVEHPSDLIVSKGD---PATLNCKAEGRPTPTIQWLKNGqpleTDKDDPRSHRIVLPSGSLfflrVVHGRKGRSDEGV 77

                           90       100
                   ....*....|....*....|..
gi 1958767848   98 YQCIATNSFGTIVSREAKLQFA 119
Cdd:cd07693     78 YVCVAHNSLGEAVSRNASLEVA 99

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.82 E-value: 2.09e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIeVQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIaRKARRHK-----SSGILEIPNFQQEDAGSYECVAEN 299
Cdd:pfam07679    1 PKF-TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFK-DGQPL-RSSDRFKvtyegGTYTLTISNVQPDDSGKYTCVATN 77

                           90
                   ....*....|..
gi 1958767848  300 SRGKNIAKGQVT 311
Cdd:pfam07679   78 SAGEAEASAELT 89

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: 2.11e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTW-RKGREILRENERITISEDGN-LRIINVTKSDAGSYTCIATNH-FGTASSTGNVVV 494
Cdd:cd20970     14 AREGENATFMCRAEGSPEPEISWtRNGNLIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGvPGSVEKRITLQV 92

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: 63.28 E-value: 2.76e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  327 VAMEESVFWECKANGRPKPTYRWLKNGDPLLTR-ERI-QIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd20952     11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKdERItTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 62.98 E-value: 3.28e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  326 HVAMEesVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQGTlNITIVNL--SDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05723     10 HESMD--IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEH-NLQVLGLvkSDEGFYQCIAENDVGNAQASAQLII 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 62.97 E-value: 3.66e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFPldsEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVV--EGSLLINNPNKtQDSGTYQCIAT 103
Cdd:pfam13927    2 PVITVSPSSVTVR---EGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSgsNSTLTISNVTR-SDAGTYTCVAS 77


                   .
gi 1958767848  104 N 104
Cdd:pfam13927   78 N 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 62.20 E-value: 5.15e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  323 NDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLT----RERIQIEQGTLNITIVNLSDAGMYQCVAEN 388
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 62.80 E-value: 5.20e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   30 QEPSHVMfpLDSEEKKVkLSCEV-KGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTqDSGTYQCIATNSFGT 108
Cdd:cd05724      2 VEPSDTQ--VAVGEMAV-LECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKS-DEGTYKCVATNMVGE 77


                   ....*...
gi 1958767848  109 IVSREAKL 116
Cdd:cd05724     78 RESRAARL 85

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: 62.02 E-value: 9.74e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPI-ARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLH-NGKPLqGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79

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: 1.33e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  243 VKLECFALGNPVPTILWRRaDGKPIARKA----RRHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd00096      1 VTLTCSASGNPPPTITWYK-NGKPLPPSSrdsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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: 61.70 E-value: 1.33e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  336 ECKANGRPKPTYRWLKNG---DPLLTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSVI 402
Cdd:cd04978     20 ICEAEGNPQPTITWRLNGvpiEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFLHVL 89

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: 61.36 E-value: 1.51e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQI---EQG--TLNITIVNLSDAGMYQCVAENKH 390
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlvrENGrhSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1958767848  391 GVIYASAELSV 401
Cdd:cd05744     81 GENSFNAELVV 91

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: 61.09 E-value: 1.72e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   596 PGPPEAVTIDEITDTTAQLSWRPGPDNH--SPITMYVIQARTPFSvGWQAVSTVPelvdgKTFTATVVGLNPWVEYEFRT 673
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGS-EWKEVNVTP-----SSTSYTLTGLKPGTEYEFRV 74


                    ....*....
gi 1958767848   674 VAANVIGIG 682
Cdd:smart00060   75 RAVNGAGEG 83

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: 61.08 E-value: 1.87e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  237 AEKGSTVKLECFALGNPVPTILWRRADGKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05876      7 ALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLG 72

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 60.51 E-value: 2.82e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  803 PPASIFARSLSATDIEVFWASPIGKNrGRIQGYEVKYWrHDDKEENARKIRTVGNQTSTKITNLKGNALYHLSVKAYNSA 882
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGN-GPITGYEVEYR-PKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 1958767848  883 GTGPSS 888
Cdd:pfam00041   80 GEGPPS 85

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: 60.31 E-value: 3.29e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  229 VQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAKG 308
Cdd:cd05728      3 LKVISDTEADIGSSLRWECKASGNPRPAYRWLK-NGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ...
gi 1958767848  309 QVT 311
Cdd:cd05728     82 ELA 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: 60.33 E-value: 4.09e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADGK--PIARKARRH--KSSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd05763      6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGGTdfPAARERRMHvmPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISAN 85


                   ....
gi 1958767848  308 GQVT 311
Cdd:cd05763     86 ATLT 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: 59.92 E-value: 4.12e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITIsEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05728      9 TEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV-EAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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: 59.68 E-value: 6.61e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRAdGKPIARKAR----RHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd05747     10 PRSLTVSEGESARFSCDVDGEPAPTVTWMRE-GQIIVSSQRhqitSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQ 88


                   ....
gi 1958767848  308 GQVT 311
Cdd:cd05747     89 FTLT 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: 59.34 E-value: 7.17e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  324 DIHVAMEESVFWECKA-NGRPKPTYRWLKNGDPL-LTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGV-IYASAEL 399
Cdd:cd05724      6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLnLDNERVRIvDDGNLLIAEARKSDEGTYKCVATNMVGErESRAARL 85


                   ..
gi 1958767848  400 SV 401
Cdd:cd05724     86 SV 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: 59.35 E-value: 7.25e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  234 TVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05731      4 STMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMG 72

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: 59.08 E-value: 8.50e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHKSS-GILEIPNFQQEDAGSYECVAENSR 301
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMK-DGKPLGHSSRVQILSeDVLVIPSVKREDKGMYQCFVRNDG 77

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: 59.48 E-value: 9.58e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  332 SVFWECKANGRPKPTYRWLKNGDPLLTRERI-----QIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05857     21 TVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIggykvRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 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: 59.18 E-value: 9.90e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  421 VGGEVVIECKPKASPRPVYTWRK-GREILRENERITISEDGN-LRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd05730     17 LGQSVTLACDADGFPEPTMTWTKdGEPIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAE 87

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: 59.06 E-value: 1.18e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKAR-RHKSSG-ILEIPNFQQEDAGSYECVAEN 299
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRyIVRENGtTLTIRNIRRSDMGIYLCIASN 78

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: 58.77 E-value: 1.43e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  332 SVFWECKANGRPKPTYRWLKNGDPLLTRERIQI----EQG-TLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05729     21 KVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGtkveEKGwSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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: 57.79 E-value: 2.06e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  327 VAMEESVFWECKANGRPKPTYRWLKNgDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05725      9 VLVDDSAEFQCEVGGDPVPTVRWRKE-DGELPKGRYEIlDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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: 57.95 E-value: 2.34e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  226 KIEVQFPETVPAEKGSTVKLECFALG-NPVPTILWRRADGK-PiarkARRHKSSGILEIPNFQQEDAGSYECVAENSRgk 303
Cdd:cd05754      2 QVTVEEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTlP----SRAMDFNGILTIRNVQLSDAGTYVCTGSNML-- 75

                           90
                   ....*....|
gi 1958767848  304 NIAKGQVTFY 313
Cdd:cd05754     76 DTDEATATLY 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: 58.02 E-value: 2.47e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWkLNGTDVdIGMDFRYSVVE-GSLLINNPNKtQDSGTYQCIATNSFGTIVSREAKLQ 117
Cdd:cd20968     13 EGLKAVLPCTTMGNPKPSVSW-IKGDDL-IKENNRIAVLEsGSLRIHNVQK-EDAGQYRCVAKNSLGIAYSKPVTIE 86

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: 58.06 E-value: 2.67e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   34 HVMFPLDSeekkVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVE--GSLLIN---NPNKTQDSGTYQCIATNSFGT 108
Cdd:cd05875     11 YIVDPRDN----ILIECEAKGNPVPTFHWTRNGKFFNVAKDPRVSMRRrsGTLVIDfrgGGRPEDYEGEYQCFARNKFGT 86


                   ....*....
gi 1958767848  109 IVSREAKLQ 117
Cdd:cd05875     87 ALSNKIRLQ 95

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: 57.21 E-value: 4.45e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDP---LLTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSVI 402
Cdd:cd05867     15 ETARLDCQVEGIPTPNITWSINGAPiegTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHVV 89

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: 56.42 E-value: 4.64e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  425 VVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVS 65

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: 4.73e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  315 QPNwVQIINdihvaMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVI 393
Cdd:cd20957      7 DPP-VQTVD-----FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQIlSEDVLVIPSVKREDKGMYQCFVRNDGDSA 80


                   ....*.
gi 1958767848  394 YASAEL 399
Cdd:cd20957     81 QATAEL 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 56.80 E-value: 5.07e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  499 KVMVPPSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGHLIdfdKDGDHFERVGGDSAGDLMIRNIQLKHAGKYVCMV 577
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTI--TWYKNGEPI---SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 57.18 E-value: 5.40e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRE------RIQIEQGTLNITIV-----NLSDAGMYQC 384
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprshRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                           90
                   ....*....|....*...
gi 1958767848  385 VAENKHGVIY-ASAELSV 401
Cdd:cd07693     81 VAHNSLGEAVsRNASLEV 98

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: 56.89 E-value: 6.09e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  423 GEVVIECKPKASPRPVYTWRKGR-EILRENERITISeDGNLRIINVTKS-DAGSYTCIATNHFGTASST 489
Cdd:cd05849     20 GKVSVNCRARANPFPIYKWRKNNlDIDLTNDRYSMV-GGNLVINNPDKYkDAGRYVCIVSNIYGKVRSR 87

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: 56.87 E-value: 6.10e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  315 QPNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPL-LTRERIQIEQGTLNITIVNLS--DAGMYQCVAENKHG 391
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLqYAADRSTCEAGVGELHIQDVLpeDHGTYTCLAKNAAG 80

                           90
                   ....*....|
gi 1958767848  392 VIYASAELSV 401
Cdd:cd20976     81 QVSCSAWVTV 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: 55.97 E-value: 9.52e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   504 PSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGhlIDFDKDGDHFERVGGDSAGDLMIRNIQLKHAGKYVCMVQTSVDK 583
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEV--TWYKQG--GKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 1958767848   584 LSAAADLIV 592
Cdd:smart00410   77 ASSGTTLTV 85

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 62.33 E-value: 9.59e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  595 PPGPPEAVTIDEITDTTAQLSWRPGPDNHspITMYVIQARTPFSVGWQAVSTVPELvdgkTFTATvvGLNPWVEYEFRTV 674
Cdd:COG3401    232 PPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRVYRSNSGDGPFTKVATVTTT----SYTDT--GLTNGTTYYYRVT 303

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  675 AANviGIGEPSRPSEkrrTEEALPEVT----PANVSGGGGSKSELVITWETVPEELQNgrgfGYVVAFRPHGKMIWmlTV 750
Cdd:COG3401    304 AVD--AAGNESAPSN---VVSVTTDLTppaaPSGLTATAVGSSSITLSWTASSDADVT----GYNVYRSTSGGGTY--TK 372

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  751 LASADASRYvFRNESVRPFSPFEVKVGVFNNKG-EGPFSPTTLVYSAE----EEPTKPPASIFARSLSATDIEVFWASPI 825
Cdd:COG3401    373 IAETVTTTS-YTDTGLTPGTTYYYKVTAVDAAGnESAPSEEVSATTASaasgESLTASVDAVPLTDVAGATAAASAASNP 451

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  826 GKNRGRIQGYEVKYWRHDDKEENARKIRTVGNQTSTKITNLKGNALYHLSVKAYNSAGTGPSSAAVNVTTRKPPPSQPPG 905
Cdd:COG3401    452 GVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVT 531

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1958767848  906 NIIWNS--SDSKIILNWDQVKALDNESEVKGYKVLYRWNRQSSTSVI 950
Cdd:COG3401    532 GASPVTvgASTGDVLITDLVSLTTSASSSVSGAGLGSGNLYLITTLG 578

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: 56.10 E-value: 1.02e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSrTLLKRVTLVKvGGEVVIECKPKASPRPVYTW-RKGREILRENERITISED-GNLRIINVTKSDAGSYTCIATNHF 483
Cdd:cd20976      2 PSFS-SVPKDLEAVE-GQDFVAQCSARGKPVPRITWiRNAQPLQYAADRSTCEAGvGELHIQDVLPEDHGTYTCLAKNAA 79

                           90
                   ....*....|.
gi 1958767848  484 GTASSTGNVVV 494
Cdd:cd20976     80 GQVSCSAWVTV 90

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: 55.71 E-value: 1.07e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPL-LTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05745      3 QTVDFLCEAQGYPQPVIAWTKGGSQLsVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 55.97 E-value: 1.15e-09

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848    46 VKLSCEVKGNPKPHIRWKLNGTDVdIGMDFRYSVVE----GSLLINNPNKtQDSGTYQCIATNSFGTiVSREAKLQ 117
Cdd:smart00410   12 VTLSCEASGSPPPEVTWYKQGGKL-LAESGRFSVSRsgstSTLTISNVTP-EDSGTYTCAATNSSGS-ASSGTTLT 84

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: 55.88 E-value: 1.17e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRK-GREILreNERITIsEDGN--LRIINVTKSDAGSYTCIATNHFGTASSTGNVV 493
Cdd:cd05731      5 TMVLRGGVLLLECIAEGLPTPDIRWIKlGGELP--KGRTKF-ENFNktLKIENVSEADSGEYQCTASNTMGSARHTISVT 81


                   ..
gi 1958767848  494 VK 495
Cdd:cd05731     82 VE 83

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: 56.21 E-value: 1.18e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  325 IHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIE----QGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd05747     13 LTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITsteyKSTFEISKVQMSDEGNYTVVVENSEG 83

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: 55.87 E-value: 1.38e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  130 STVSVRRGQGMVLLCGPPPHSGELSYAWIFNEHPSYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNTV 200
Cdd:cd05724      5 SDTQVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMV 75

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: 55.48 E-value: 1.48e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  232 PETVPAEKGSTVKLECFA-LGNPVPTILWRRaDGKPIARKARRHK--SSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRK-DGQPLNLDNERVRivDDGNLLIAEARKSDEGTYKCVATNMVGERESR 81

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: 55.72 E-value: 1.77e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  231 FPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHKSS---GILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd20976      7 VPKDLEAVEGQDFVAQCSARGKPVPRITWIR-NAQPLQYAADRSTCEagvGELHIQDVLPEDHGTYTCLAKNAAGQVSCS 85


                   ....
gi 1958767848  308 GQVT 311
Cdd:cd20976     86 AWVT 89

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: 55.58 E-value: 2.08e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGN----LRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05744     12 VQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhsLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 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: 54.89 E-value: 2.44e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  414 KRVTLVKVGGEVVIECKPK-ASPRPVYTWRKGREILRENERITISEDG----NLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRttqsSLLISNVTKEDAGTYTCVVNNPGGSATL 82


                   .
gi 1958767848  489 T 489
Cdd:pfam00047   83 S 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: 55.33 E-value: 2.57e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAM---EESVFWECKANGRPKPTYRWLKNGDPLLTRE--RIQIEQGTLNITIVN-LSDAGMYQCVAENK 389
Cdd:cd05848      2 PVFVQEPDDAIFPTdsdEKKVILNCEARGNPVPTYRWLRNGTEIDTESdyRYSLIDGNLIISNPSeVKDSGRYQCLATNS 81


                   ....
gi 1958767848  390 HGVI 393
Cdd:cd05848     82 IGSI 85

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: 2.75e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFpldSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSvVEGSL--LINNPNKTQDSGTYQCIAT 103
Cdd:cd20972      2 PQFIQKLRSQEV---AEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIH-QEGDLhsLIIAEAFEEDTGRYSCLAT 77


                   ....*
gi 1958767848  104 NSFGT 108
Cdd:cd20972     78 NSVGS 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: 54.71 E-value: 2.77e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRK-GREILREneRITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05725      7 QVVLVDDSAEFQCEVGGDPVPTVRWRKeDGELPKG--RYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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: 54.53 E-value: 3.31e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVVK 495
Cdd:cd05876      5 LVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTVE 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: 54.94 E-value: 3.76e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  320 QIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLT-RERIQIEQGTLNITI--VNLSDAGMYQCVAENKHGVIYAS 396
Cdd:cd05730      8 QSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESgEEKYSFNEDGSEMTIldVDKLDEAEYTCIAENKAGEQEAE 87


                   ....*...
gi 1958767848  397 AELSVIAE 404
Cdd:cd05730     88 IHLKVFAK 95

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: 54.50 E-value: 4.13e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  320 QIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQG-----TLNITIVNLSDAGMYQCVAENKHGVIY 394
Cdd:cd20973      2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDedglcSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                   ....*..
gi 1958767848  395 ASAELSV 401
Cdd:cd20973     82 CSAELTV 88

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: 54.12 E-value: 4.36e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  424 EVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05723     14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

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: 54.13 E-value: 4.41e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRKGREILRENERITI---SEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05748      4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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: 54.39 E-value: 4.50e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREILREN-ERITISEDGN----LRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd05892     15 GDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCN 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: 54.38 E-value: 5.00e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   41 SEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFGTIV 110
Cdd:cd04978     12 SPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLL 81

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: 54.17 E-value: 5.08e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADG--KPIARKARRhkSSGILEIPNFQQEDAGSYECVAENSRGKNIAK 307
Cdd:cd20968      6 PTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDliKENNRIAVL--ESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSK 81

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: 54.16 E-value: 5.19e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   803 PPASIFARSLSATDIEVFWASPIGKN-RGRIQGYEVKYWRHDDKEEnarKIRTVGNQTSTKITNLKGNALYHLSVKAYNS 881
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGiTGYIVGYRVEYREEGSEWK---EVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 1958767848   882 AGTG 885
Cdd:smart00060   80 AGEG 83

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: 5.79e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  416 VTLVKVGGEVVIECKPKASPRPVYTWRK-GREI---LRENERITISEDGnLRIINVTKSDAGSYTCIATNHFGTAS 487
Cdd:cd20949      8 VTTVKEGQSATILCEVKGEPQPNVTWHFnGQPIsasVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQVNSIAS 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: 54.01 E-value: 7.00e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLLKRVtlVKVGGEVVIECKPKASPRPVYTWRKGREILRENER--ITISEDG--NLRIINVTKSDAGSYTCIATN 481
Cdd:cd20975      1 PTFKVSLMDQS--VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRrfAEEAEGGlcRLRILAAERGDAGFYTCKAVN 78


                   ...
gi 1958767848  482 HFG 484
Cdd:cd20975     79 EYG 81

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: 53.78 E-value: 7.19e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  336 ECKANGRPKPTYRWLKNG--DPLLTRER---IQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSVI 402
Cdd:cd05763     20 ECAATGHPTPQIAWQKDGgtDFPAARERrmhVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTVL 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: 53.58 E-value: 8.51e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEP-SHVMFpldsEEKKVKLSCEVKGNPKPHIRWKLNGTDVD-IGMDFRYSVVEGS----LLINNPNKtQDSGTYQ 99
Cdd:cd20951      1 PEFIIRLqSHTVW----EKSDAKLRVEVQGKPDPEVKWYKNGVPIDpSSIPGKYKIESEYgvhvLHIRRVTV-EDSAVYS 75

                           90
                   ....*....|..
gi 1958767848  100 CIATNSFGTIVS 111
Cdd:cd20951     76 AVAKNIHGEASS 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: 53.18 E-value: 1.00e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLtRERIQIE--QGTLNITIVNLSDAGMYQCVAENKHGViyASAELSVIAE 404
Cdd:cd05731     11 GVLLLECIAEGLPTPDIRWIKLGGELP-KGRTKFEnfNKTLKIENVSEADSGEYQCTASNTMGS--ARHTISVTVE 83

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: 53.36 E-value: 1.10e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   21 YTLHGPvfvqePSHVMFPLDSeekkVKLSCEVKGNPKPHIRWKLNGTDVD-IGMDFRYSVVEGSLLINNPnKTQDSGTYQ 99
Cdd:cd05867      1 YWTRRP-----QSHLYGPGET----ARLDCQVEGIPTPNITWSINGAPIEgTDPDPRRHVSSGALILTDV-QPSDTAVYQ 70

                           90
                   ....*....|.
gi 1958767848  100 CIATNSFGTIV 110
Cdd:cd05867     71 CEARNRHGNLL 81

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: 53.40 E-value: 1.12e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  337 CKANGRPKPTYRWLKNGDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVIYA 395
Cdd:cd20968     21 CTTMGNPKPSVSWIKGDDLIKENNRIAVlESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

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: 53.27 E-value: 1.20e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFpldSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEG---SLLINNPNKtQDSGTYQCIA 102
Cdd:cd05744      1 PHFLQAPGDLEV---QEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTK-RDAGIYTCIA 76

                           90
                   ....*....|....
gi 1958767848  103 TNSFGtIVSREAKL 116
Cdd:cd05744     77 RNRAG-ENSFNAEL 89

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: 53.40 E-value: 1.24e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  423 GEVVIECKPKASPRPVYTWRK-GREI-LRENERITISeDGNLRIINVTKS-DAGSYTCIATNHFGTASST 489
Cdd:cd04967     20 KKVALNCRARANPVPSYRWLMnGTEIdLESDYRYSLV-DGTLVISNPSKAkDAGHYQCLATNTVGSVLSR 88

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: 52.56 E-value: 2.19e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPE-TVpaEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRH-----KSSGI----LEIPNFQQEDAGSYE 294
Cdd:cd20956      2 PVLLETFSEqTL--QPGPSVSLKCVASGNPLPQITWTL-DGFPIPESPRFRvgdyvTSDGDvvsyVNISSVRVEDGGEYT 78


                   ....*....
gi 1958767848  295 CVAENSRGK 303
Cdd:cd20956     79 CTATNDVGS 87

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: 52.11 E-value: 2.37e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  240 GSTVKLECFALGNPVPTILWRRADGkPIARKARRHKSS----GILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWG-HVPDSARVSITSeggyGTLTIRDVKESDQGAYTCEAINTRG 66

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: 52.09 E-value: 2.61e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  337 CKANGRPKPTYRWLKNGDPLL--TRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05764     22 CKARGDPEPAIHWISPEGKLIsnSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 52.25 E-value: 2.92e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  328 AMEESVFWECKANGRPKPTYRWLKNGDP--LLTRERIQIEQGTLNIT-IVNLSDAGMYQCVAENKHGVI 393
Cdd:cd04967     17 SDEKKVALNCRARANPVPSYRWLMNGTEidLESDYRYSLVDGTLVISnPSKAKDAGHYQCLATNTVGSV 85

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: 52.18 E-value: 2.96e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQ---------GTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd20956     17 PSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVGDyvtsdgdvvSYVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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: 52.17 E-value: 3.34e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  332 SVFWECKANGRPKPTYRWLKNGDPLLTRE--RIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05856     21 SVRLKCVASGNPRPDITWLKDNKPLTPPEigENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 92

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: 51.44 E-value: 3.94e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  341 GRPKPTYRWLKNGDPLLTRERIQIEQG----TLNITIVNLSDAGMYQCVAENKHGViyASAELSVI 402
Cdd:cd05748     18 GRPTPTVTWSKDGQPLKETGRVQIETTasstSLVIKNAKRSDSGKYTLTLKNSAGE--KSATINVK 81

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: 51.93 E-value: 4.05e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRK--GREI-----LRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd20954     13 VAAGQDVMLHCQADGFPTPTVTWKKatGSTPgeykdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIGSGLS 89

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: 51.74 E-value: 4.27e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTDVdIGMDFRYSVVEGSLLINNPNKTQ-DSGTYQCIATNSFGTIVSREAKLQ 117
Cdd:cd20970     16 EGENATFMCRAEGSPEPEISWTRNGNLI-IEFNTRYIVRENGTTLTIRNIRRsDMGIYLCIASNGVPGSVEKRITLQ 91

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: 51.54 E-value: 4.48e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  333 VFWECKANGRPKPTYRWLKNGDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05852     20 VIIECKPKAAPKPKFSWSKGTELLVNNSRISIwDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

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: 4.51e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  409 SRTLLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd20957      3 SATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQA 82


                   ..
gi 1958767848  489 TG 490
Cdd:cd20957     83 TA 84

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: 51.31 E-value: 5.06e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  235 VPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd04969     12 ILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK 80

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 51.49 E-value: 5.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  503 PPSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGHLIdfdKDGDHF--ERVGGDSAgdLMIRNIQLKHAGKYVCMVQTS 580
Cdd:pfam07679    6 KPKDVEVQEGESARFTCTVTGTPDPEV--SWFKDGQPL---RSSDRFkvTYEGGTYT--LTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 1958767848  581 VDKLSAAADLIV 592
Cdd:pfam07679   79 AGEAEASAELTV 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: 51.54 E-value: 5.53e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADG------KPIARKAR-RHKSSGILEIPNFQQEDAGSYECVAENSRGKN 304
Cdd:cd20954      8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKATGstpgeyKDLLYDPNvRILPNGTLVFGHVQKENEGHYLCEAKNGIGSG 87


                   ...
gi 1958767848  305 IAK 307
Cdd:cd20954     88 LSK 90

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: 5.70e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLTRE-----RIQIEQG--TLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd20951     16 SDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgkyKIESEYGvhVLHIRRVTVEDSAVYSAVAKNIHGEASSSASVVV 93

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: 51.05 E-value: 6.15e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  240 GSTVKLECFALGNPVPTILWRrADGKPIARKA---RRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05867     14 GETARLDCQVEGIPTPNITWS-INGAPIEGTDpdpRRHVSSGALILTDVQPSDTAVYQCEARNRHG 78

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: 50.86 E-value: 6.25e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   29 VQEPSHVMFPLDseeKKVKLSCEVKGNPKPHIRWKLNGTDVDIGmdfRYSVVE-GSLLINNPnKTQDSGTYQCIATNSFG 107
Cdd:cd05725      1 VKRPQNQVVLVD---DSAEFQCEVGGDPVPTVRWRKEDGELPKG---RYEILDdHSLKIRKV-TAGDMGSYTCVAENMVG 73


                   ..
gi 1958767848  108 TI 109
Cdd:cd05725     74 KI 75

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: 51.50 E-value: 6.49e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  327 VAMEESVFWECKANGRPKPTYRWLKNGD--------PLLTRERIQIEQ-GTLNITIVNLSDAGMYQCVAENKHGVIYASA 397
Cdd:cd05726     11 VALGRTVTFQCETKGNPQPAIFWQKEGSqnllfpyqPPQPSSRFSVSPtGDLTITNVQRSDVGYYICQALNVAGSILAKA 90


                   ....
gi 1958767848  398 ELSV 401
Cdd:cd05726     91 QLEV 94

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: 51.04 E-value: 6.83e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLlkRVTLVKVGGEVVIECKPKASPRPVYTW-RKGREiLRENERITISEDGNLR---IINVTKSDAGSYTCIATN 481
Cdd:cd20972      2 PQFIQKL--RSQEVAEGSKVRLECRVTGNPTPVVRWfCEGKE-LQNSPDIQIHQEGDLHsliIAEAFEEDTGRYSCLATN 78

                           90
                   ....*....|...
gi 1958767848  482 HFGTASSTGNVVV 494
Cdd:cd20972     79 SVGSDTTSAEIFV 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: 6.99e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRTLlkRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITI----SEDG--NLRIINVTKSDAGSYTCIA 479
Cdd:cd20951      1 PEFIIRL--QSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKykieSEYGvhVLHIRRVTVEDSAVYSAVA 78

                           90
                   ....*....|....*.
gi 1958767848  480 TNHFGTASSTGNVVVK 495
Cdd:cd20951     79 KNIHGEASSSASVVVE 94

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: 50.97 E-value: 7.22e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKPKA-SPRPVYTWRK-GREILREN-ERITI---SEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNV 492
Cdd:cd05750     11 VQEGSKLVLKCEATSeNPSPRYRWFKdGKELNRKRpKNIKIrnkKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNV 90


                   ..
gi 1958767848  493 VV 494
Cdd:cd05750     91 TV 92

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: 51.01 E-value: 7.22e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  240 GSTVKLECFALGNPVPTILWRRaDGKPIARK--ARRHKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLK-DNKPLTPPeiGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGE 83

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: 50.79 E-value: 7.29e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  324 DIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd05851     10 DTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKG 77

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: 51.08 E-value: 7.93e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  423 GEVVIECKPKASPRPVYTWR-KGREILRENERITISEDGNLRIINVTKS-DAGSYTCIATNHFGTASS 488
Cdd:cd05850     21 EKVTLACRARASPPATYRWKmNGTELKMEPDSRYRLVAGNLVISNPVKAkDAGSYQCLASNRRGTVVS 88

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: 51.02 E-value: 8.39e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYS--VVEGSLLINNPN----KTQDSGTYQCIATNSFGTiVSREAKL 116
Cdd:cd20956     19 VSLKCVASGNPLPQITWTLDGFPIPESPRFRVGdyVTSDGDVVSYVNissvRVEDGGEYTCTATNDVGS-VSHSARI 94

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: 51.07 E-value: 8.54e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  406 PDFSRT--LLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGN----LRIINVTKSDAGSYTCIA 479
Cdd:cd05729      1 PRFTDTekMEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEkgwsLIIERAIPRDKGKYTCIV 80

                           90
                   ....*....|....*
gi 1958767848  480 TNHFGTASSTGNVVV 494
Cdd:cd05729     81 ENEYGSINHTYDVDV 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: 50.87 E-value: 9.01e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNG-------DPLLTRERiqiEQGTLNITIVNLSD---AGMYQCVAENKHG 391
Cdd:cd05733     17 DNITIKCEAKGNPQPTFRWTKDGkffdpakDPRVSMRR---RSGTLVIDNHNGGPedyQGEYQCYASNELG 84

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: 50.29 E-value: 9.44e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLT-RERIQIEQGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd05876     11 QSLVLECIAEGLPTPTVKWLRPSGPLPPdRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLG 72

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: 50.78 E-value: 9.73e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHK----SSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05738      6 PQLKVVEKARTATMLCAASGNPDPEISWFK-DFLPVDTATSNGRikqlRSGALQIENSEESDQGKYECVATNSAG 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: 50.66 E-value: 9.89e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQG----TLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSVG 81

                           90
                   ....*....|
gi 1958767848  392 VIYASAELSV 401
Cdd:cd20972     82 SDTTSAEIFV 91

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: 49.87 E-value: 1.06e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  337 CKANGRPKPTYRWLKNGDPLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELS 400
Cdd:cd05746      5 CSAQGDPEPTITWNKDGVQVTESGKFHIsPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 50.36 E-value: 1.08e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848   48 LSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFGTIVS 111
Cdd:cd05868     19 LICRANGNPKPSISWLTNGVPIEIAPTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLA 82

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: 50.47 E-value: 1.09e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  233 ETVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKAR-RHK--SSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd20969     10 QQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNgRLTvfPDGTLEVRYAQVQDNGTYLCIAANAGGN 83

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: 50.87 E-value: 1.12e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  224 EPKIEVQFPETVPAEkgstvkLECFALGNPVPTILWRRADGKPIAR--KARRHKSSGILEIPNFQQED------AGSYEC 295
Cdd:cd20955      7 EPTNRIDFSNSTGAE------IECKASGNPMPEIIWIRSDGTAVGDvpGLRQISSDGKLVFPPFRAEDyrqevhAQVYAC 80

                           90
                   ....*....|..
gi 1958767848  296 VAENSRGKNIAK 307
Cdd:cd20955     81 LARNQFGSIISR 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: 50.14 E-value: 1.21e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  240 GSTVKLECFALGNPVPTILWrRADGKPI---ARKARRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd04978     14 GETGELICEAEGNPQPTITW-RLNGVPIepaPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

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: 1.24e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  218 GVMGEYEPkIEVQFPETVPAEKgstVKLECFALGNPVPTILWRRADGK-PIARKARRHKSSGILEIPN-FQQEDAGSYEC 295
Cdd:cd04967      1 GPVFEEQP-DDTIFPEDSDEKK---VALNCRARANPVPSYRWLMNGTEiDLESDYRYSLVDGTLVISNpSKAKDAGHYQC 76


                   ....*..
gi 1958767848  296 VAENSRG 302
Cdd:cd04967     77 LATNTVG 83

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: 50.17 E-value: 1.33e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEkGSTVKLECFALGNPVPTILWRRADGKPIARKAR-RHKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd05764      1 PLITRHTHELRVLE-GQRATLRCKARGDPEPAIHWISPEGKLISNSSRtLVYDNGTLDILITTVKDTGAFTCIASNPAGE 79


                   ...
gi 1958767848  304 NIA 306
Cdd:cd05764     80 ATA 82

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 54.64 E-value: 1.42e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  167 DNRRFVSQETG-NLYIAKVEKADVGNYTCVVTNTVTSHqvlgpptpLILRNDGVMGEYEPKIE-VQFPETVpaEKGSTVK 244
Cdd:PHA02785    71 DNDRIIPIDNGsNMLILNPTQSDSGIYICITKNETYCD--------MMSLNLTIVSVSESNIDlISYPQIV--NERSTGE 140

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  245 LEC-----FALGNPVPTILWRradGKPIARKAR-RHKSSGILEIPNFQQEDAGSYECVAENSRGKN------IAKGQVTF 312
Cdd:PHA02785   141 MVCpninaFIASNVNADIIWS---GHRRLRNKRlKQRTPGIITIEDVRKNDAGYYTCVLKYIYGDKtynvtrIVKLEVRD 217

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  313 YAQPNWVQIINDIHVAMEESVFWECKANGRPKPT---YRWLKNG-----------------DPLLTRERIQIEQGTLNIT 372
Cdd:PHA02785   218 RIIPPTMQLPEGVVTSIGSNLTIACRVSLRPPTTdadVFWISNGmyyeeddedgdgrisvaNKIYTTDKRRVITSRLNIN 297

                          250       260
                   ....*....|....*....|
gi 1958767848  373 IVNLSDAGMYQCVAENKHGV 392
Cdd:PHA02785   298 PVKEEDATTFTCMAFTIPSI 317

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: 50.34 E-value: 1.43e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  415 RVTLVKVGGEVVIECKPKASPRPVYTWRK-GREIL-------RENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTA 486
Cdd:cd05726      7 RDQVVALGRTVTFQCETKGNPQPAIFWQKeGSQNLlfpyqppQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGSI 86

                           90
                   ....*....|
gi 1958767848  487 SSTGNVVVKD 496
Cdd:cd05726     87 LAKAQLEVTD 96

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: 50.10 E-value: 1.43e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFpldSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSL--LINNPNKTQDSGTYQCIAT 103
Cdd:cd20990      1 PHFLQAPGDLTV---QEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVhsLIIEPVTSRDAGIYTCIAT 77


                   ....
gi 1958767848  104 NSFG 107
Cdd:cd20990     78 NRAG 81

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: 50.34 E-value: 1.55e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  320 QIINDIHV--AMEESVFWECKANGRPKPTYRW-LKNGDPLLTRERIQIEQGTLNITIVNLS-DAGMYQCVAENKHGVIYA 395
Cdd:cd05849      7 QPIDTIYPeeSTEGKVSVNCRARANPFPIYKWrKNNLDIDLTNDRYSMVGGNLVINNPDKYkDAGRYVCIVSNIYGKVRS 86


                   ....*.
gi 1958767848  396 S-AELS 400
Cdd:cd05849     87 ReATLS 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: 50.30 E-value: 1.56e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  235 VPAekGSTVKLECFALGNPVPTILWRRaDGKP-----IARKARRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05729     16 LPA--ANKVRLECGAGGNPMPNITWLK-DGKEfkkehRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYG 85

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: 49.98 E-value: 1.70e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  337 CKANGRPKPTYRWLKNGDPLL---TRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSVI 402
Cdd:cd05868     21 CRANGNPKPSISWLTNGVPIEiapTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLANAFVNVL 89

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: 49.10 E-value: 1.83e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  243 VKLECFALGNPVPTILWRRaDGKPIARKARRHKS-SGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNK-DGVQVTESGKFHISpEGYLAIRDVGVADQGRYECVARNTIG 60

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: 49.17 E-value: 2.04e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  239 KGSTVKLECFALGNPVPTILWRRAdGKPIARKaRRHK--SSGILEIPNFQQEDAGSYECVAENSRGKNIAKGQVT 311
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKG-GSQLSVD-RRHLvlSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLT 73

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 54.25 E-value: 2.08e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  362 IQIEQGTlNITIVN--LSDAGMYQCVAENKHGVIYASAELSVIAESPD------FSRTLLKRVTlvkvgGEVV---IECK 430
Cdd:PHA02785    76 IPIDNGS-NMLILNptQSDSGIYICITKNETYCDMMSLNLTIVSVSESnidlisYPQIVNERST-----GEMVcpnINAF 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  431 PKASPRPVYTWRKGREIlrENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVVKDPTKVMVPPSSMD-- 508
Cdd:PHA02785   150 IASNVNADIIWSGHRRL--RNKRLKQRTPGIITIEDVRKNDAGYYTCVLKYIYGDKTYNVTRIVKLEVRDRIIPPTMQlp 227

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1958767848  509 ----VTVGESIVLPCQVT-HDHSLDIVFTWTFNG-HLIDFDKDGD 547
Cdd:PHA02785   228 egvvTSIGSNLTIACRVSlRPPTTDADVFWISNGmYYEEDDEDGD 272

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: 50.10 E-value: 2.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   25 GPVFVQEPSH-VMFpldSEEKKVKLSCEVKGNPKPHIRW-KLNGTDVDIGMDFRYSVVEGSLLINnPNKTQD------SG 96
Cdd:cd20955      1 GPVFLKEPTNrIDF---SNSTGAEIECKASGNPMPEIIWiRSDGTAVGDVPGLRQISSDGKLVFP-PFRAEDyrqevhAQ 76

                           90       100
                   ....*....|....*....|.
gi 1958767848   97 TYQCIATNSFGTIVSREAKLQ 117
Cdd:cd20955     77 VYACLARNQFGSIISRDVHVR 97

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: 49.80 E-value: 2.60e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQfPETVPAEKGSTVKLECFALGNPVPTILWRRADGK------PIARKARRHK--SSGILEIPNFQQEDAGSYECV 296
Cdd:cd05734      2 PRFVVQ-PNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSgvpqfqHIVPLNGRIQllSNGSLLIKHVLEEDSGYYLCK 80

                           90
                   ....*....|.
gi 1958767848  297 AENSRGKNIAK 307
Cdd:cd05734     81 VSNDVGADISK 91

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: 49.06 E-value: 3.52e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  224 EPKIevQFPETVPAEKGSTVKLECFALGNPVPTILWRRA-------DGKPIAR-KARRHKSSGILEIPNFQQEDAGSYEC 295
Cdd:cd05732      2 QPKI--TYLENQTAVELEQITLTCEAEGDPIPEITWRRAtrgisfeEGDLDGRiVVRGHARVSSLTLKDVQLTDAGRYDC 79

                           90
                   ....*....|
gi 1958767848  296 VAENSRGKNI 305
Cdd:cd05732     80 EASNRIGGDQ 89

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: 3.60e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTDV--DIGMDFRYSVVEGSLLINNPnKTQDSGTYQCIATNSFGT 108
Cdd:cd20949     13 EGQSATILCEVKGEPQPNVTWHFNGQPIsaSVADMSKYRILADGLLINKV-TQDDTGEYTCRAYQVNSI 80

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: 48.93 E-value: 3.92e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  410 RTLLKRVTLVKVGGEVVIECKPKASPRPVYTW---RKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTA 486
Cdd:cd20969      5 RDRKAQQVFVDEGHTVQFVCRADGDPPPAILWlspRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGND 84


                   ....*...
gi 1958767848  487 SSTGNVVV 494
Cdd:cd20969     85 SMPAHLHV 92

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: 48.54 E-value: 4.32e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  315 QPNwVQIINDIHVAMEESVFWECKANGrPKPTYRWLKNGDPLLTRERIQIEQG--TLNITIVNLSDAGMYQCVAEN 388
Cdd:cd05740      1 KPF-ISSNNSNPVEDKDAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGnrTLTLLNVTREDAGAYQCEISN 74

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: 49.15 E-value: 4.37e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  330 EESVFWECKANGRPKPTYRWLKNGDPLLTRE--RIQIEQGTLNIT-IVNLSDAGMYQCVAENKHGVI 393
Cdd:cd05850     20 EEKVTLACRARASPPATYRWKMNGTELKMEPdsRYRLVAGNLVISnPVKAKDAGSYQCLASNRRGTV 86

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: 48.70 E-value: 4.48e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  414 KRVTLVKVGGEVVIECKPKASPRPVYTWrkgreiLRENERITISEDGN-------LRIINVTKSDAGSYTCIATNHFGTA 486
Cdd:cd05856     11 RRVIARPVGSSVRLKCVASGNPRPDITW------LKDNKPLTPPEIGEnkkkkwtLSLKNLKPEDSGKYTCHVSNRAGEI 84


                   ....*...
gi 1958767848  487 SSTGNVVV 494
Cdd:cd05856     85 NATYKVDV 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: 48.01 E-value: 4.64e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 48.55 E-value: 4.78e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  502 VPPSSMDVTVGESIVLPCQVTHDHSLDIVfTWTFNGHLIDFDKdgdhfERVGGDSAGDLMIRNIQLKHAGKYVCMVQTSV 581
Cdd:cd05724      2 VEPSDTQVAVGEMAVLECSPPRGHPEPTV-SWRKDGQPLNLDN-----ERVRIVDDGNLLIAEARKSDEGTYKCVATNMV 75

                           90
                   ....*....|..
gi 1958767848  582 -DKLSAAADLIV 592
Cdd:cd05724     76 gERESRAARLSV 87

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: 48.70 E-value: 5.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIeVQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRHKSSGIL----------EIPNFQ-QEDAGSY 293
Cdd:cd07693      1 PRI-VEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLK-NGQPLETDKDDPRSHRIVlpsgslfflrVVHGRKgRSDEGVY 78


                   ....*....
gi 1958767848  294 ECVAENSRG 302
Cdd:cd07693     79 VCVAHNSLG 87

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: 48.37 E-value: 5.20e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848   49 SCEVKGNPKPHIRWKLNGTDvdIGMDFRYSVVEGSLLINNPNkTQDSGTYQCIATNSFGTI 109
Cdd:cd05728     20 ECKASGNPRPAYRWLKNGQP--LASENRIEVEAGDLRITKLS-LSDSGMYQCVAENKHGTI 77

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: 48.83 E-value: 5.24e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   39 LDSEEKKVkLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVV--EGSLLIN--NPNKTQD-SGTYQCIATNSFGTIVS 111
Cdd:cd05874     13 VDPRENIV-IQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTMKpnTGTLVINimNGEKAEAyEGVYQCTARNERGAAVS 89

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: 48.70 E-value: 5.30e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  235 VPAekGSTVKLECFALGNPVPTILWRRaDGKPIAR-------KARRHKSSGILE--IPNfqqeDAGSYECVAENSRG 302
Cdd:cd05857     16 VPA--ANTVKFRCPAAGNPTPTMRWLK-NGKEFKQehriggyKVRNQHWSLIMEsvVPS----DKGNYTCVVENEYG 85

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: 48.39 E-value: 5.93e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  237 AEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARRH---KSSGILEIPNFQQEDAGSYECVAENSRGKNIAKGQVTFY 313
Cdd:cd05730     15 ANLGQSVTLACDADGFPEPTMTWTK-DGEPIESGEEKYsfnEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVF 93


                   ..
gi 1958767848  314 AQ 315
Cdd:cd05730     94 AK 95

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: 47.88 E-value: 7.29e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   27 VFVQEPSHVMFPLDSEekkVKLSCEVKGNPKPHIRWKLNGTDVdIGMDFRYSVVE-GSLLINNPNKtQDSGTYQCIATNS 105
Cdd:cd20952      1 IILQGPQNQTVAVGGT---VVLNCQATGEPVPTISWLKDGVPL-LGKDERITTLEnGSLQIKGAEK-SDTGEYTCVALNL 75


                   ...
gi 1958767848  106 FGT 108
Cdd:cd20952     76 SGE 78

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: 47.86 E-value: 7.97e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWR--KGReILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05764     10 LRVLEGQRATLRCKARGDPEPAIHWIspEGK-LISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 48.06 E-value: 8.78e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNG-------DPLLTrerIQIEQGTLNITIVNLSDA----GMYQCVAENKHG 391
Cdd:cd05874     17 ENIVIQCEAKGKPPPSFSWTRNGthfdidkDPKVT---MKPNTGTLVINIMNGEKAeayeGVYQCTARNERG 85

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: 47.96 E-value: 8.82e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFA-LGNPVPTILWRRADGKPI----ARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGKNIA 306
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIeslkVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82


                   .
gi 1958767848  307 K 307
Cdd:pfam00047   83 S 83

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: 47.57 E-value: 9.78e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  427 IECKPKASPRPVYTWRKGREILRENERITI--SEDGN--LRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd20973     17 FDCKVEGYPDPEVKWMKDDNPIVESRRFQIdqDEDGLcsLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

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: 47.70 E-value: 1.05e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   50 CEVKGNPKPHIRWKLNGTDVDIGM-DFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFGTIVSREAKL 116
Cdd:cd05738     21 CAASGNPDPEISWFKDFLPVDTATsNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRYSAPANL 88

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: 1.11e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  337 CKANGR-PKPTYRWLKNGDPLLTR--ERIQIEQGT----LNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05750     21 CEATSEnPSPRYRWFKDGKELNRKrpKNIKIRNKKknseLQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

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: 46.94 E-value: 1.21e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  515 IVLPCQVTHDHSLDIvfTWTFNGHLIDFDKDGDHFERVGGdsaGDLMIRNIQLKHAGKYVCMVQTSV 581
Cdd:cd00096      1 VTLTCSASGNPPPTI--TWYKNGKPLPPSSRDSRRSELGN---GTLTISNVTLEDSGTYTCVASNSA 62

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). 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 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with 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-2 and -1 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.

Pssm-ID: 409448 Cd Length: 102 Bit Score: 47.82 E-value: 1.23e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  500 VMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFTWTF----NGHLIDFDKDGDHFERVGGDSAGDLMIRNIQLKHAGKYVC 575
Cdd:cd05862      4 QLSPPKPVELLVGEKLVLNCTARTELNVGVDFQWDYpgkkEQRRASVRRRRKQQSSEATEFSSTLTIDNVTLSDKGLYTC 83

                           90
                   ....*....|....*..
gi 1958767848  576 MVQTSVDKLSAAADLIV 592
Cdd:cd05862     84 AASSGPMFKKNSTSVIV 100

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: 47.40 E-value: 1.27e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKP--IARKAR--RHKSSGILEIPN---FQQEDAGSYECVA 297
Cdd:cd05733      1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTK-DGKFfdPAKDPRvsMRRRSGTLVIDNhngGPEDYQGEYQCYA 79

                           90
                   ....*....|
gi 1958767848  298 ENSRGKNIAK 307
Cdd:cd05733     80 SNELGTAISN 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.00 E-value: 1.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  323 NDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQieqgtlnITIVNLSDAGMYQCVAENKHGVI-YASAELSV 401
Cdd:pfam13895    7 SPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFF-------TLSVSAEDSGTYTCVARNGRGGKvSNPVELTV 79

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: 47.31 E-value: 1.56e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  337 CKANGRPKPTYRWLKNG---DPLLTRERI-QIEQGTLNITIVNLSDAGMYQCVAENKHGVIY-ASAELSV 401
Cdd:cd05738     21 CAASGNPDPEISWFKDFlpvDTATSNGRIkQLRSGALQIENSEESDQGKYECVATNSAGTRYsAPANLYV 90

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: 46.74 E-value: 2.09e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  237 AEKGSTVKLECFALG-NPVPTILWRRaDGKPIAR------KARRHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAKGQ 309
Cdd:cd05750     11 VQEGSKLVLKCEATSeNPSPRYRWFK-DGKELNRkrpkniKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGN 89


                   ..
gi 1958767848  310 VT 311
Cdd:cd05750     90 VT 91

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: 46.86 E-value: 2.26e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   32 PSHVMFPLDS---EEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMD-FRYSVVEGSLLINNPnKTQDSGTYQCIATNSFG 107
Cdd:cd20976      2 PSFSSVPKDLeavEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADrSTCEAGVGELHIQDV-LPEDHGTYTCLAKNAAG 80


                   ....*....
gi 1958767848  108 TiVSREAKL 116
Cdd:cd20976     81 Q-VSCSAWV 88

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: 46.89 E-value: 2.30e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  320 QIINDIHVAMEESVFWECKANGRPKPTYRWLKNG-------DPLLTRERiqiEQGTLNITIVNLSDA----GMYQCVAEN 388
Cdd:cd05875      6 QSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGkffnvakDPRVSMRR---RSGTLVIDFRGGGRPedyeGEYQCFARN 82


                   ...
gi 1958767848  389 KHG 391
Cdd:cd05875     83 KFG 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 46.02 E-value: 2.58e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  126 TRTRSTVSVRRGQGMVLLC----GPPPhsgelSYAWIFNEHP--SYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTN 198
Cdd:pfam13927    5 TVSPSSVTVREGETVTLTCeatgSPPP-----TITWYKNGEPisSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 46.54 E-value: 2.77e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  427 IECKPKASPRPVYTWRKG---REILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTA-SSTGNVVVK 495
Cdd:cd05738     19 MLCAASGNPDPEISWFKDflpVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGTRySAPANLYVR 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.85 E-value: 2.98e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  225 PKIEVQFPETVpaeKGSTVKLECFALGNPVPTILWRRaDGKPIarkarrhKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:pfam13895    2 PVLTPSPTVVT---EGEPVTLTCSAPGNPPPSYTWYK-DGSAI-------SSSPNFFTLSVSAEDSGTYTCVARNGRGG 69

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: 45.25 E-value: 4.26e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSvVEGSLLINNPNkTQDSGTYQCIATNSFG 107
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHIS-PEGYLAIRDVG-VADQGRYECVARNTIG 60

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: 45.96 E-value: 4.28e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  324 DIHVAMEESVFWECKANGRPKPTYRWLKNGDPLL---TRERIQIEQGTLNITIVNLSDAGMYQCVAENK 389
Cdd:cd20970     11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIefnTRYIVRENGTTLTIRNIRRSDMGIYLCIASNG 79

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: 4.44e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  337 CKANGRPKPTYRWLKNG---DPLLTRERIQIEQGT-LNITIVNLSDAGMYQCVAENKHGV 392
Cdd:cd05736     22 CHAEGIPLPRVQWLKNGmdiNPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGV 81

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: 45.66 E-value: 4.54e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDGnLRIINVTKSdaGSYTCIATNHFGTASSTGNVVVK 495
Cdd:cd05739      9 VMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNV-LELTNIYES--ANYTCVAISSLGMIEATAQVTVK 82

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: 45.64 E-value: 4.56e-06

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  440 TWRKGREILRENERITISEDGNLRIINVTK-SDAGSYTCIATNHFG-TASSTGNVVV 494
Cdd:cd20958     33 TWEKDGRRLPLNHRQRVFPNGTLVIENVQRsSDEGEYTCTARNQQGqSASRSVFVKV 89

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: 46.09 E-value: 4.68e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  424 EVVIECKPKASPRPVYTW-RKGREILRENERITISEDGNLRIINVTKS-DAGSYTCIATNHFGTASS 488
Cdd:cd05848     21 KVILNCEARGNPVPTYRWlRNGTEIDTESDYRYSLIDGNLIISNPSEVkDSGRYQCLATNSIGSILS 87

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: 46.50 E-value: 4.91e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  240 GSTVKLECFALGNPVPTILWRRADGKPI---------ARKARRH-------KSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd20940     15 GDSVELHCEAVGSPIPEIQWWFEGQEPNeicsqlwdgARLDRVHinatyhqHATSTISIDNLTEEDTGTYECRASNDPDR 94


                   .
gi 1958767848  304 N 304
Cdd:cd20940     95 N 95

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. 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. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 45.18 E-value: 5.41e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  237 AEKGSTVKLECFALGNPVPTILWRRADgkpiarkaRRHKSSGILEIPNFQQEDAGSYECVAENS-RGKNIAKGQVT 311
Cdd:cd20948      7 YLSGENLNLSCHAASNPPAQYSWTING--------TFQTSSQELFLPAITENNEGTYTCSAHNSlTGKNISLVLSV 74

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: 5.58e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  229 VQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKA--RRHKSSGI--LEIPNFQQEDAGSYECVAENSRGKN 304
Cdd:cd20972      5 IQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFC-EGKELQNSPdiQIHQEGDLhsLIIAEAFEEDTGRYSCLATNSVGSD 83


                   ....*.
gi 1958767848  305 IAKGQV 310
Cdd:cd20972     84 TTSAEI 89

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: 45.69 E-value: 5.62e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  223 YEPKIEVQ-----FPETVPAEKgstVKLECFALGNPVPTILWRrADGKPI--ARKARRHKSSGILEIPNFQQ-EDAGSYE 294
Cdd:cd05850      1 YGPVFEEQpsstlFPEGSAEEK---VTLACRARASPPATYRWK-MNGTELkmEPDSRYRLVAGNLVISNPVKaKDAGSYQ 76

                           90
                   ....*....|...
gi 1958767848  295 CVAENSRGKNIAK 307
Cdd:cd05850     77 CLASNRRGTVVSR 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: 45.72 E-value: 6.58e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  240 GSTVKLECFALGNPVPTILWRRADG-------KPIARKARRHKS-SGILEIPNFQQEDAGSYECVAENSRGKNIAKGQV 310
Cdd:cd05726     14 GRTVTFQCETKGNPQPAIFWQKEGSqnllfpyQPPQPSSRFSVSpTGDLTITNVQRSDVGYYICQALNVAGSILAKAQL 92

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: 45.23 E-value: 8.07e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   35 VMFPLDSEEKK---VKLSCEVKGNPKPHIRWKlngtDVDIGMDFRYSVVEGSLLINNPNKTQ-DSGTYQCIATNSFG 107
Cdd:cd04968      5 VRFPADTYALKgqtVTLECFALGNPVPQIKWR----KVDGSPSSQWEITTSEPVLEIPNVQFeDEGTYECEAENSRG 77

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: 45.36 E-value: 8.55e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  224 EPKIevQFPETVPA-EKGSTVKLECFALGNPVPTILWRRA-----------DGKPIARKARRHKSsgiLEIPNFQQEDAG 291
Cdd:cd05869      2 KPKI--TYVENQTAmELEEQITLTCEASGDPIPSITWRTStrnisseektlDGHIVVRSHARVSS---LTLKYIQYTDAG 76

                           90
                   ....*....|....
gi 1958767848  292 SYECVAENSRGKNI 305
Cdd:cd05869     77 EYLCTASNTIGQDS 90

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: 45.18 E-value: 8.59e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  702 PANVSGGGGSKSELVITWEtvPEELQNGRGFGYVVAFRPHGKMIWMLTVLASADASRYVFRNesVRPFSPFEVKVGVFNN 781
Cdd:cd00063      4 PTNLRVTDVTSTSVTLSWT--PPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTG--LKPGTEYEFRVRAVNG 79

                           90
                   ....*....|
gi 1958767848  782 KGEGPFSPTT 791
Cdd:cd00063     80 GGESPPSESV 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 44.69 E-value: 8.76e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVmfpldSEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFrysvvegslLINNPNKTqDSGTYQCIATNS 105
Cdd:pfam13895    2 PVLTPSPTVV-----TEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNF---------FTLSVSAE-DSGTYTCVARNG 66

                           90
                   ....*....|..
gi 1958767848  106 FGTIVSREAKLQ 117
Cdd:pfam13895   67 RGGKVSNPVELT 78

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: 44.92 E-value: 9.12e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRKGREI----LRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd05763     11 IRAGSTARLECAATGHPTPQIAWQKDGGTdfpaARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 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: 45.00 E-value: 1.10e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKN-----GD--PLLTRERIQI-EQGTLNITIVNLSDAGMYQCVAE 387
Cdd:cd20954      2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKAtgstpGEykDLLYDPNVRIlPNGTLVFGHVQKENEGHYLCEAK 81


                   .
gi 1958767848  388 N 388
Cdd:cd20954     82 N 82

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: 44.79 E-value: 1.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  229 VQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIaRKARRHK----SSGI--LEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05744      4 LQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQL-NGKPV-RPDSAHKmlvrENGRhsLIIEPVTKRDAGIYTCIARNRAG 81


                   ..
gi 1958767848  303 KN 304
Cdd:cd05744     82 EN 83

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: 44.76 E-value: 1.12e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848   45 KVKLSCEVKGNPKPHIRWKLNGTDVDIGMdfRYSVVE-GSLLINNPNKTqDSGTYQCIATNSFGT 108
Cdd:cd04969     19 DVIIECKPKASPKPTISWSKGTELLTNSS--RICILPdGSLKIKNVTKS-DEGKYTCFAVNFFGK 80

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: 44.49 E-value: 1.20e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGtDVDIGMDFRYSVVEGSLLINNPNKTqDSGTYQCIATNSFGTIVS 111
Cdd:cd05723     11 ESMDIVFECEVTGKPTPTVKWVKNG-DVVIPSDYFKIVKEHNLQVLGLVKS-DEGFYQCIAENDVGNAQA 78

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: 44.87 E-value: 1.20e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEPSHVMFpldSEEKKVKLSCEVKGNPKP-HIRWKLNGTDVDIGM-DFRYSVVEGSLLINNPnKTQDSGTYQCIAT 103
Cdd:cd20979      1 PVLKEQPAEVLF---REGQPTVLECVTEGGDQGvKYSWLKDGKSFNWQEhNVAQRKDEGSLVFLKP-QASDEGQYQCFAE 76

                           90
                   ....*....|....
gi 1958767848  104 NSFGTIVSREAKLQ 117
Cdd:cd20979     77 TPAGVASSRVISFR 90

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: 44.94 E-value: 1.21e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848   48 LSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVV-EGSLLINNPNKTQDSGTYQCIATNSFG 107
Cdd:cd05736     20 LRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIaNGSELHISNVRYEDTGAYTCIAKNEGG 80

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: 44.47 E-value: 1.30e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  331 ESVFWECKANGR-PKPTYRWLKNGDPLLTRERIQieQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELS 400
Cdd:cd05754     17 ADVSFICRAKSKsPAYTLVWTRVNGTLPSRAMDF--NGILTIRNVQLSDAGTYVCTGSNMLDTDEATATLY 85

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: 44.12 E-value: 1.31e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  234 TVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARR----HKSSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd05748      1 TIVVRAGESLRLDIPIKGRPTPTVTWSK-DGQPLKETGRVqietTASSTSLVIKNAKRSDSGKYTLTLKNSAGE 73

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: 44.82 E-value: 1.33e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  411 TLLKRVTLVKvGGEVVIECKPKASPRPVYTWRKGREILRENE-----RITISED---GNLRIINVTKSDAGSYTCIATNH 482
Cdd:cd05732      6 TYLENQTAVE-LEQITLTCEAEGDPIPEITWRRATRGISFEEgdldgRIVVRGHarvSSLTLKDVQLTDAGRYDCEASNR 84


                   ..
gi 1958767848  483 FG 484
Cdd:cd05732     85 IG 86

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: 1.44e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  425 VVIECKPKASPRPVYTWRK-GREI-LRENERITISEDGNLRIINVTKSDA----GSYTCIATNHFGTASS 488
Cdd:cd05733     19 ITIKCEAKGNPQPTFRWTKdGKFFdPAKDPRVSMRRRSGTLVIDNHNGGPedyqGEYQCYASNELGTAIS 88

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: 44.78 E-value: 1.46e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREILRE--NERITISEDGNLRIINVT-----KSDAGSYTCIATN-HFGT-ASSTGNV 492
Cdd:cd05722     16 GGPVVLNCSAESDPPPKIEWKKDGVLLNLvsDERRQQLPNGSLLITSVVhskhnKPDEGFYQCVAQNeSLGSiVSRTARV 95


                   ..
gi 1958767848  493 VV 494
Cdd:cd05722     96 TV 97

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.92 E-value: 1.50e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERITISedgnlriiNVTKSDAGSYTCIATNH 482
Cdd:pfam13895    9 TVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTL--------SVSAEDSGTYTCVARNG 66

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: 44.56 E-value: 1.55e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVqFPETVPAEKGSTVKLECFALGNPVPTILWRRAD---GKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSR 301
Cdd:cd05736      1 PVIRV-YPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGmdiNPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEG 79


                   .
gi 1958767848  302 G 302
Cdd:cd05736     80 G 80

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. 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). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with 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 also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

Pssm-ID: 409404 Cd Length: 102 Bit Score: 44.84 E-value: 1.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  499 KVMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFTWTF----NGHLI----DFDKDGDHfervGGDSAGDLMIRNIQLKHA 570
Cdd:cd05742      4 ELSPNAEPTVLPQGETLVLNCTANVNLNEVVDFQWTYpsekEGKLAllkpDIKVDWSE----PGEFVSTLTIPEATLKDS 79

                           90       100
                   ....*....|....*....|..
gi 1958767848  571 GKYVCMVQTSVDKLSAAADLIV 592
Cdd:cd05742     80 GTYTCAARSGVMKKEKQTSVSV 101

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: 44.47 E-value: 1.63e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848   35 VMFPLDSEekkVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEGSLLINNPnKTQDSGTYQCIATNSFGTI 109
Cdd:cd05856     14 IARPVGSS---VRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNL-KPEDSGKYTCHVSNRAGEI 84

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 48.85 E-value: 1.69e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  853 RTVGNQTSTKITNLKGNALYHLSVKAYNSAGTGPSSAAVNVTTRKPPPSQPPGNIIWNSSDSKIILNWDQVKALDneseV 932
Cdd:COG3401    186 TVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD----A 261

                           90       100
                   ....*....|....*....|....*.
gi 1958767848  933 KGYKVlYRWNRQSSTSVI--ETNKTS 956
Cdd:COG3401    262 TGYRV-YRSNSGDGPFTKvaTVTTTS 286

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: 44.52 E-value: 1.72e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   45 KVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVE--GSLLINNPNKTQDSGTYQCIATNSFGTI 109
Cdd:cd05729     21 KVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEekGWSLIIERAIPRDKGKYTCIVENEYGSI 87

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: 44.32 E-value: 1.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  229 VQFPETVPAEKGSTVKLECFALGNPVPTILWRrADGKPIaRKARRHK----SSGI--LEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd20990      4 LQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQ-LDGKPI-RPDSAHKmlvrENGVhsLIIEPVTSRDAGIYTCIATNRAG 81


                   ..
gi 1958767848  303 KN 304
Cdd:cd20990     82 QN 83

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: 44.24 E-value: 1.86e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREILRENERITISeDGNLRIINVTKSDAGSYTCIATNHFGTASSTGNVVVK 495
Cdd:cd05851     16 GQNVTLECFALGNPVPVIRWRKILEPMPATAEISMS-GAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

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: 44.15 E-value: 1.90e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   47 KLSCEVKGNPKPHIRW-KLNGTDVDIGMDFRYSVV--EGSLLINNPnKTQDSGTYQCIATNSFGTIVS 111
Cdd:cd05763     18 RLECAATGHPTPQIAWqKDGGTDFPAARERRMHVMpeDDVFFIVDV-KIEDTGVYSCTAQNSAGSISA 84

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: 44.08 E-value: 1.95e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRK---GRE--ILRENE---RITISEDGNLRIINVTKSDAGSYTCIATNHFG 484
Cdd:cd05765     12 VKVGETASFHCDVTGRPQPEITWEKqvpGKEnlIMRPNHvrgNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 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: 2.01e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  240 GSTVKLECFALGNPVPTILWRRaDGK--PIARKARRHkSSGILEIPNFQQ-EDAGSYECVAENSRGkNIAKGQV 310
Cdd:cd20958     15 GQTLRLHCPVAGYPISSITWEK-DGRrlPLNHRQRVF-PNGTLVIENVQRsSDEGEYTCTARNQQG-QSASRSV 85

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: 2.18e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  411 TLLKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENE-----RITISED---GNLRIINVTKSDAGSYTCIATNH 482
Cdd:cd05869      6 TYVENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEktldgHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNT 85


                   ..
gi 1958767848  483 FG 484
Cdd:cd05869     86 IG 87

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: 44.01 E-value: 2.24e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  327 VAME-ESVFWECKANGRPKPTYRWLKNGDPL---LTRERIQIEQGTLNITIV-----NLSDAGMYQCVAENKH--GVIYA 395
Cdd:cd05722     12 VAMRgGPVVLNCSAESDPPPKIEWKKDGVLLnlvSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQNESlgSIVSR 91


                   ....*.
gi 1958767848  396 SAELSV 401
Cdd:cd05722     92 TARVTV 97

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: 44.08 E-value: 2.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  417 TLVKVGGEVVIECKPKASPRPVYTWRKGREILRENE-----RITISEDGNLRIINV-----TKSDAGSYTCIATNHFGTA 486
Cdd:cd07693     10 LIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprsHRIVLPSGSLFFLRVvhgrkGRSDEGVYVCVAHNSLGEA 89


                   ..
gi 1958767848  487 SS 488
Cdd:cd07693     90 VS 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: 43.17 E-value: 3.14e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848   46 VKLSCEVKGNPKPHIRW-KLNGtdvdigmdfrySVVEGSLLINNPNKT--------QDSGTYQCIATNSFGTI 109
Cdd:cd05731     13 LLLECIAEGLPTPDIRWiKLGG-----------ELPKGRTKFENFNKTlkienvseADSGEYQCTASNTMGSA 74

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: 43.60 E-value: 3.27e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   26 PVFVQEP-SHVMFPLDSeekkVKLSCEVKGNPKPHIRWKLNGTDVDIGMDfRYSVVEG-----SLLINNPNKTqDSGTYQ 99
Cdd:cd05892      1 PMFIQKPqNKKVLEGDP----VRLECQISAIPPPQIFWKKNNEMLQYNTD-RISLYQDncgriCLLIQNANKK-DAGWYT 74

                           90
                   ....*....|....*..
gi 1958767848  100 CIATNSFGtIVSREAKL 116
Cdd:cd05892     75 VSAVNEAG-VVSCNARL 90

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: 3.37e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  235 VPAEKGSTVKLECFALGNPVPTILWRRADgKPIARKARRHK-SSGILEIPNFQQEDAGSYECVAENSRGK 303
Cdd:cd05852     12 ILAAKGGRVIIECKPKAAPKPKFSWSKGT-ELLVNNSRISIwDDGSLEILNITKLDEGSYTCFAENNRGK 80

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: 43.33 E-value: 3.39e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  418 LVKVGGEVVIECKPKASPRPV-YTWRK-GREI-LRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd20979     11 LFREGQPTVLECVTEGGDQGVkYSWLKdGKSFnWQEHNVAQRKDEGSLVFLKPQASDEGQYQCFAETPAGVASS 84

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: 3.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQGT-----LNITIVNLSDAGMYQCVAENKH 390
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEgglcrLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1958767848  391 GVIYASAELSV 401
Cdd:cd20975     81 GARQCEARLEV 91

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: 43.22 E-value: 4.02e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  418 LVKVGGEVVIECKPKASPRPVYTWRKGREILREN-ERITISEDGNLRIINVTKSDAGSYTCIATNH 482
Cdd:cd04979      7 SVKEGDTVILSCSVKSNNAPVTWIHNGKKVPRYRsPRLVLKTERGLLIRSAQEADAGVYECHSGER 72

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: 43.17 E-value: 4.38e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLL---TRERIQIEQGTLNITI--VNLSDAGMYQCVAENKH 390
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRpdsAHKMLVRENGVHSLIIepVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1958767848  391 GVIYASAELSV 401
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: 42.95 E-value: 4.81e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  502 VPPSSMDVTVGESIVLPCQVTHDHSLDIVfTWTFNG-HLIDFDKDGDHFERVGGDSagdLMIRNIQLKHAGKYVCMVQTS 580
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGPDV-TWSKEGgTLIESLKVKHDNGRTTQSS---LLISNVTKEDAGTYTCVVNNP 76

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: 42.48 E-value: 5.09e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIE----QGTLNITIVNLSDAGMYQCVAENKHGVIYA 395
Cdd:cd05743      2 ETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITseggYGTLTIRDVKESDQGAYTCEAINTRGMVFG 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: 42.79 E-value: 5.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAekGSTVKLECFALGNPVPTILWRRaDGKPIarkaRRHKSSGILEIPNFQQ-----------EDAGSYECVAENS 300
Cdd:cd20951      9 SHTVWE--KSDAKLRVEVQGKPDPEVKWYK-NGVPI----DPSSIPGKYKIESEYGvhvlhirrvtvEDSAVYSAVAKNI 81


                   ..
gi 1958767848  301 RG 302
Cdd:cd20951     82 HG 83

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 43.02 E-value: 5.43e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  497 PTKVMVPPSSMDVTVGESIVLPCQVTHdhSLDIVFTWtfnghlIDFDK---DGDHFERVGGDSAGDLMIRNIQLKHAGKY 573
Cdd:cd05762      1 PPQIIQFPEDMKVRAGESVELFCKVTG--TQPITCTW------MKFRKqiqEGEGIKIENTENSSKLTITEGQQEHCGCY 72

                           90       100
                   ....*....|....*....|....*.
gi 1958767848  574 VCMVQTSVDKLSAAADLIVRGPPGPP 599
Cdd:cd05762     73 TLEVENKLGSRQAQVNLTVVDKPDPP 98

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: 42.23 E-value: 5.49e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTDVDIgmDFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFGT 108
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSV--DRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGS 65

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: 42.45 E-value: 6.06e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  502 VPPSSMDVTVGESIVLPCQVTHDHSLdivFTWTFNGHlidfDKDGDHFERVGGDSAGDLMIRNIQLKHAGKYVC 575
Cdd:cd04979      1 TSFKQISVKEGDTVILSCSVKSNNAP---VTWIHNGK----KVPRYRSPRLVLKTERGLLIRSAQEADAGVYEC 67

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: 42.76 E-value: 6.92e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLT-----RERIqIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd20969     18 HTVQFVCRADGDPPPAILWLSPRKHLVSaksngRLTV-FPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 43.02 E-value: 7.12e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEKGSTVKLECFALGNPVPTILWRR----------ADGKPIARKAR------RHKSSGILEIPNFQQE 288
Cdd:cd05858      1 PILQAGLPANTSVVVGTDAEFVCKVYSDAQPHIQWLKhvekngskygPDGLPYVEVLKtagvntTDKEIEVLYLRNVTFE 80

                           90
                   ....*....|....
gi 1958767848  289 DAGSYECVAENSRG 302
Cdd:cd05858     81 DAGEYTCLAGNSIG 94

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: 42.69 E-value: 7.15e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  340 NGRPKPTYRWLKNGDPLLTRER-----------IQIEQGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd20950     23 DGSPPSEYTWFKDGVVMPTNPKstrafsnssysLDPTTGELVFDPLSASDTGEYSCEARNGYG 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: 42.63 E-value: 7.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  224 EPKIEVQFPETVPAEKgstVKLECFALGNPVPTILWRRADGKPIARKARRHKSSGILEIPN-FQQEDAGSYECVAENSRG 302
Cdd:cd05849      6 EQPIDTIYPEESTEGK---VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNpDKYKDAGRYVCIVSNIYG 82


                   .
gi 1958767848  303 K 303
Cdd:cd05849     83 K 83

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: 42.33 E-value: 7.81e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  421 VGGEVVIECKPKaSPRPVYTWRK------GREILRENERITISEDGnLRIINVTKSDAGSYTCIATNH 482
Cdd:cd05871     11 EGNSTFLECLPK-SPQATVKWLFqrggdqRKEEVKSEERLIVTDRG-LLLRSLQRSDAGVYTCQAVEH 76

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: 42.48 E-value: 7.85e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  341 GRPKPTYRWLKNGDPL-----LTRERIQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd20959     29 GDLPLNIRWTLDGQPIsddlgITVSRLGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 42.39 E-value: 8.34e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848   52 VKGNPKPHIRWKLNGTDVD----IGMDFRYSVV-----EGSLLINNPNKTqDSGTYQCIATNSFGT 108
Cdd:cd04971     22 VRGNPKPTLTWYHNGAVLNesdyIRTEIHYEAAtpteyHGCLKFDNPTHV-NNGNYTLVASNEYGQ 86

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: 42.38 E-value: 8.71e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848  419 VKVGGEVVIECKPkASPRPVYTWRKGREILRENERITISEDG-NLRIINVTKSDAGSYTCIATN 481
Cdd:cd05740     12 VEDKDAVTLTCEP-ETQNTSYLWWFNGQSLPVTPRLTLSNGNrTLTLLNVTREDAGAYQCEISN 74

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: 42.39 E-value: 8.94e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKPKASPRPVYTWRKGREILREN--ERITISEDG--NLRIINVTKSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd20990     12 VQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDsaHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAGQNSFNLELVV 91

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: 42.24 E-value: 1.01e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  414 KRVTLVKvGGEVVIECK-PKASPRPVYTWRK---GREILREN---ERITISEDGNLRIINVTKSDAGS---YTCIATN 481
Cdd:cd20965     10 KEKKPVE-GKPFKLDCNvPPGYPKPTIEWKKqlvSDSSKADTildRRITISPNGDLYFTNVTKEDVSTdykYVCVAKT 86

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: 41.71 E-value: 1.01e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  423 GEVV-IECKPKASPRPVYTWRKGREILRENERITISED---GNLRIINVTKSDAGSYTCIATNHFGT 485
Cdd:cd05743      1 GETVeFTCVATGVPTPIINWRLNWGHVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAINTRGM 67

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: 42.27 E-value: 1.01e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  425 VVIECKPKASPRPVYTWRKGREILR--ENERITI-SEDGNLRIINVTKSDA----GSYTCIATNHFGTASST 489
Cdd:cd05875     19 ILIECEAKGNPVPTFHWTRNGKFFNvaKDPRVSMrRRSGTLVIDFRGGGRPedyeGEYQCFARNKFGTALSN 90

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: 42.10 E-value: 1.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  903 PPGNI-IWNSSDSKIILNWDqvKALDNESEVKGYKVLYRWNRQSSTSVIET---NKTSVELS-LPFDEDYIIEIKPFSDG 977
Cdd:cd00063      3 PPTNLrVTDVTSTSVTLSWT--PPEDDGGPITGYVVEYREKGSGDWKEVEVtpgSETSYTLTgLKPGTEYEFRVRAVNGG 80

                           90
                   ....*....|.
gi 1958767848  978 GDGSSSEQIRI 988
Cdd:cd00063     81 GESPPSESVTV 91

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: 42.27 E-value: 1.06e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  245 LECFALGNPVPTILWRRaDGK--PIARKAR--RHKSSGILEIpNFQ-----QEDAGSYECVAENSRGKNIA 306
Cdd:cd05875     21 IECEAKGNPVPTFHWTR-NGKffNVAKDPRvsMRRRSGTLVI-DFRgggrpEDYEGEYQCFARNKFGTALS 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: 41.82 E-value: 1.25e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEG---SLLINNPNkTQDSGTYQCIATNSFG 107
Cdd:cd05891     15 EGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGkyaSLTIKGVT-SEDSGKYSINVKNKYG 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: 41.77 E-value: 1.29e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  414 KRVTLVKVGGEVVIECKPKA-SPRPVYTWRKGREILRENERitiSEDGNLRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd05754      8 PRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPSRAM---DFNGILTIRNVQLSDAGTYVCTGSNMLDTDEAT 81

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 41.63 E-value: 1.36e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  702 PANVSGGGGSKSELVITWEtvPEELQNGRGFGYVVAFRPHGKMIWMLTVLASADASRYVFRNesVRPFSPFEVKVGVFNN 781
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWT--PPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTG--LKPGTEYEVRVQAVNG 78


                   ....*..
gi 1958767848  782 KGEGPFS 788
Cdd:pfam00041   79 GGEGPPS 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: 41.71 E-value: 1.36e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   32 PSHVMFPLDSEE---KKVKLSCEVKGNPKPHIRWKLN-GTDVD-----IGMDFRYSVVE-GSLLINNPNKtQDSGTYQCI 101
Cdd:cd05734      2 PRFVVQPNDQDGiygKAVVLNCSADGYPPPTIVWKHSkGSGVPqfqhiVPLNGRIQLLSnGSLLIKHVLE-EDSGYYLCK 80

                           90
                   ....*....|.
gi 1958767848  102 ATNSFGTIVSR 112
Cdd:cd05734     81 VSNDVGADISK 91

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: 41.90 E-value: 1.37e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKPKAS-PRPVYTWRK-GREILREN--ERITISED---GNLRIINVTKSDAGSYTCIATNHFGTASSTGN 491
Cdd:cd05895     11 VAAGSKLVLRCETSSEyPSLRFKWFKnGKEINRKNkpENIKIQKKkkkSELRINKASLADSGEYMCKVSSKLGNDSASAN 90


                   ...
gi 1958767848  492 VVV 494
Cdd:cd05895     91 VTI 93

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: 41.81 E-value: 1.47e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  337 CKANGRPKPTYRWLKNGDPL--LTRERIQIEQG-TLNITI--VNLSDAGMYQCVAENKHG 391
Cdd:cd05737     23 CNVWGDPPPEVSWLKNDQALafLDHCNLKVEAGrTVYFTIngVSSEDSGKYGLVVKNKYG 82

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: 41.48 E-value: 1.58e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  422 GGEVVIECKPKASPRPVYTWRKGREIL--RENERITISEDGN-LRIINVTKSDAGSYTCIATNHFGTASSTGNVVVKD 496
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKNGMDInpKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 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: 41.76 E-value: 1.68e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848   44 KKVKLSCEVKGNPKPHIRWKLNGTDVDI-----GMDFRY---SVVEGSLLINnpnktqDSGTYQCIATNSFGTI 109
Cdd:cd05857     20 NTVKFRCPAAGNPTPTMRWLKNGKEFKQehrigGYKVRNqhwSLIMESVVPS------DKGNYTCVVENEYGSI 87

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: 41.38 E-value: 2.12e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  128 TRSTVS-----VRRGQGMVLLCGPP-PHSGELSYAWIFNEHP------SYQDNRRFVSQETGNLYIAKVEKADVGNYTCV 195
Cdd:cd04970      3 TRITLApsnadITVGENATLQCHAShDPTLDLTFTWSFNGVPidlekiEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCT 82

                           90       100
                   ....*....|....*....|
gi 1958767848  196 VTNTVTSHQ------VLGPP 209
Cdd:cd04970     83 AQTVVDSDSasatlvVRGPP 102

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: 41.07 E-value: 2.16e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  413 LKRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILreNERITISEDGNLRIINVTKSDAGSYTCIATN 481
Cdd:cd05864      8 MESLVEAKVGERVRIPVKYLGYPPPEIKWYKNGIPI--ESNHTIKAGHVLTIMEVTEKDAGNYTVVLTN 74

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: 41.22 E-value: 2.19e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTD-VDIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFG 107
Cdd:cd20969     16 EGHTVQFVCRADGDPPPAILWLSPRKHlVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGG 82

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 41.24 E-value: 2.23e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  432 KASPRPVYTWRKGREILRENERITISED----------GNLRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd04971     23 RGNPKPTLTWYHNGAVLNESDYIRTEIHyeaatpteyhGCLKFDNPTHVNNGNYTLVASNEYGQDSKS 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: 41.18 E-value: 2.28e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  418 LVKVGGEVVIECKPKASPRPVYTWRKGREI--LRENERITIS-EDGN--LRIINVTKSDAGSYTCIATNHFGTASSTGNV 492
Cdd:cd20974     11 VVLEGSTATFEAHVSGKPVPEVSWFRDGQVisTSTLPGVQISfSDGRakLSIPAVTKANSGRYSLTATNGSGQATSTAEL 90


                   ...
gi 1958767848  493 VVK 495
Cdd:cd20974     91 LVL 93

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: 40.65 E-value: 2.28e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  332 SVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQGTLNITivNLSDAGMYQCVAENKHGVIYASAELSV 401
Cdd:cd05739     14 SVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRNVLELT--NIYESANYTCVAISSLGMIEATAQVTV 81

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: 41.32 E-value: 2.35e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  422 GGEVVIECKPKASPRPVYTWR--KGR------EILRENERITISEDGNLRIINVTKSDAGSYTCIATNHFGTASS 488
Cdd:cd05734     16 GKAVVLNCSADGYPPPTIVWKhsKGSgvpqfqHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGADIS 90

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: 40.65 E-value: 2.42e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  233 ETVPaekGSTVKLECFALGNPVPTILWRRA-------DGKPIARKarrhkssgILEIPNFQQedAGSYECVAENSRGKNI 305
Cdd:cd05739      8 EVMP---GGSVNLTCVAVGAPMPYVKWMKGgeeltkeDEMPVGRN--------VLELTNIYE--SANYTCVAISSLGMIE 74


                   ....*.
gi 1958767848  306 AKGQVT 311
Cdd:cd05739     75 ATAQVT 80

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: 40.97 E-value: 2.47e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848   41 SEEKKVKLSCEVKGNPKPHIRWK-------LNGTDVDIGMDFRYSVVEGSLLINNPnKTQDSGTYQCIATNSFG 107
Cdd:cd05732     14 VELEQITLTCEAEGDPIPEITWRratrgisFEEGDLDGRIVVRGHARVSSLTLKDV-QLTDAGRYDCEASNRIG 86

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: 40.99 E-value: 2.60e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  414 KRVTLVKVGGEVVIECKPKASPRPVYTWRKGREILRENERI----TISEDGNLRIINVTKSDAGSYTCIATNHFGTASST 489
Cdd:cd05857     11 KKLHAVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIggykVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

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: 40.63 E-value: 2.76e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   44 KKVKLSCEVKGNPKPHIRWKLNGTDVDIgmDFRYSVVE-GSLLINNPNKTQDSGTYQCIATNSFGTIVSR 112
Cdd:cd20958     16 QTLRLHCPVAGYPISSITWEKDGRRLPL--NHRQRVFPnGTLVIENVQRSSDEGEYTCTARNQQGQSASR 83

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: 40.92 E-value: 3.18e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIA---RKARRHKSSGILEIPNFQ-----QEDAGSYECVAEN 299
Cdd:cd05722      8 PSDIVAMRGGPVVLNCSAESDPPPKIEWKK-DGVLLNlvsDERRQQLPNGSLLITSVVhskhnKPDEGFYQCVAQN 82

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: 40.57 E-value: 3.20e-04

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   130 STVSVRRGQGMVLLCgPPPHSGELSYAWIFNEHPSYQDNRRFVSQETGN---LYIAKVEKADVGNYTCVVTNTVTSHQ 204
Cdd:smart00410    2 PSVTVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSAS 78

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: 40.65 E-value: 3.47e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   42 EEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEG---SLLINNPNkTQDSGTYQCIATNSFGT 108
Cdd:cd05737     15 EGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGrtvYFTINGVS-SEDSGKYGLVVKNKYGS 83

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: 40.68 E-value: 3.47e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  333 VFWECKANGRPKPTYRWLKNGDPLLTRER---IQIEQGTLNITIVNLSDAGMYQCVAENKHGVIYASAE--LSVIAE 404
Cdd:cd05760     19 VTLRCHIDGHPRPTYQWFRDGTPLSDGQGnysVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSQNftLSIIDE 95

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: 40.68 E-value: 3.79e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   45 KVKLSCEVKGNPKPHIRWKLNGTDV-DIGMDFRYSVVEGSLLINnPNKTQDSGTYQCIATNSFGTIVSRE 113
Cdd:cd05760     18 RVTLRCHIDGHPRPTYQWFRDGTPLsDGQGNYSVSSKERTLTLR-SAGPDDSGLYYCCAHNAFGSVCSSQ 86

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: 40.57 E-value: 3.86e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  503 PPSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGHLIdfdKDGDHFERVGGDSAgDLMIRNIQLKHAGKYVC 575
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEI--SWTRNGNLI---IEFNTRYIVRENGT-TLTIRNIRRSDMGIYLC 74

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: 3.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   43 EKKVKLSCEVKGNPKPHIRWKL-------NGTDVDIGMDFRYSVVEGSLLINNPNKTqDSGTYQCIATNSFGTivsreaK 115
Cdd:cd05869     17 EEQITLTCEASGDPIPSITWRTstrnissEEKTLDGHIVVRSHARVSSLTLKYIQYT-DAGEYLCTASNTIGQ------D 89


                   ....*..
gi 1958767848  116 LQFAYLE 122
Cdd:cd05869     90 SQSMYLE 96

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: 40.53 E-value: 4.00e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  420 KVGGEVVIECKPKASPRPVYTWRKGREILRENERITISEDG----NLRIINVT-KSDAGSYTCIATNHFGTASSTGNVVV 494
Cdd:cd20971     14 RYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFkggyHQLIIASVtDDDATVYQVRATNQGGSVSGTASLEV 93

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 44.55 E-value: 4.34e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  581 VDKLSAAADLIVRGPPGPPEAVTIDEITDTTAQLSWRPGPDnhsPITMYVIQARTPFSVGWQAVSTVPELVDGKTFTATV 660
Cdd:COG4733    432 VTMEAGDRYLRVRLPDGTSVARTVQSVAGRTLTVSTAYSET---PEAGAVWAFGPDELETQLFRVVSIEENEDGTYTITA 508

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  661 VGLNPWVeyeFRTVAANVIgigepsrpsekrrtEEALPEVTPANVS--------GGGGSKSELVITWETVPE----ELQN 728
Cdd:COG4733    509 VQHAPEK---YAAIDAGAF--------------DDVPPQWPPVNVTtseslsvvAQGTAVTTLTVSWDAPAGavayEVEW 571

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  729 GRGFG-YVVAFRPHGKMIwmltVLASADASRYVFRnesVRPfspfevkVGVFNNKGEGPFSPTTLVYSAEEEPTKPPasi 807
Cdd:COG4733    572 RRDDGnWVSVPRTSGTSF----EVPGIYAGDYEVR---VRA-------INALGVSSAWAASSETTVTGKTAPPPAPT--- 634

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  808 farSLSAT----DIEVFWASPIGknrGRIQGYEVKYWRHDDKeENARKIRTVGNQTSTKITNLKGNALYHLSVKAYNSAG 883
Cdd:COG4733    635 ---GLTATgglgGITLSWSFPVD---ADTLRTEIRYSTTGDW-ASATVAQALYPGNTYTLAGLKAGQTYYYRARAVDRSG 707

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  884 T-GPSSAAVNVTTRKPPPSQPPGNIIWNSSDSKIILNWDQVKALDNESEVKGYKVLYRWN-RQSSTSVIETNKTSVELS 960
Cdd:COG4733    708 NvSAWWVSGQASADAAGILDAITGQILETELGQELDAIIQNATVAEVVAATVTDVTAQIDtAVLFAGVATAAAIGAEAR 786

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: 40.26 E-value: 4.39e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848   41 SEEKKVKLSCEVK-GNPKPHIRWKLNGT----DVDIGMDFRYSVVEgSLLINNPNKtQDSGTYQCIATNSFG 107
Cdd:pfam00047    9 LEGDSATLTCSAStGSPGPDVTWSKEGGtlieSLKVKHDNGRTTQS-SLLISNVTK-EDAGTYTCVVNNPGG 78

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: 40.61 E-value: 4.63e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  417 TLVKVGGEVVIECKpkASPRP----VYTWR-KGREI-LRENE----RITISED-GNLRIINVTKSDAGSYTCIATNHFGT 485
Cdd:cd04970     12 ADITVGENATLQCH--ASHDPtldlTFTWSfNGVPIdLEKIEghyrRRYGKDSnGDLEIVNAQLKHAGRYTCTAQTVVDS 89

                           90
                   ....*....|..
gi 1958767848  486 ASSTGNVVVKDP 497
Cdd:cd04970     90 DSASATLVVRGP 101

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: 4.96e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  506 SMDVTVGESIVLPCQVTHDHSlDIVFTWTFNGHLIDFDKDGDHFERVGGDSAGDLMIRNIQLKHAGKYVCMVQTSVDKLS 585
Cdd:cd05895      8 SQEVAAGSKLVLRCETSSEYP-SLRFKWFKNGKEINRKNKPENIKIQKKKKKSELRINKASLADSGEYMCKVSSKLGNDS 86


                   ....*..
gi 1958767848  586 AAADLIV 592
Cdd:cd05895     87 ASANVTI 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: 40.14 E-value: 5.04e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPL-LTRERIQIEQG-----TLNITIVNLSDAGMYQCVAENK 389
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLqYNTDRISLYQDncgriCLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1958767848  390 HGVIYASAELSV 401
Cdd:cd05892     81 AGVVSCNARLDV 92

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: 40.31 E-value: 5.25e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  243 VKLECFALGNPVPTILWRRaDGKPIARKARRHKS--SGILEIPNFQQ-EDAGSYECVAENSRGKNIAKGQVTFYA 314
Cdd:cd05848     22 VILNCEARGNPVPTYRWLR-NGTEIDTESDYRYSliDGNLIISNPSEvKDSGRYQCLATNSIGSILSREALLQFA 95

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: 39.93 E-value: 6.16e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPLLTRE-RIQIEQ-----GTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd04977     16 ESKFFLCKVSGDAKNINWVSPNGEKVLTKHgNLKVVNhgsvlSSLTIYNANINDAGIYKCVATNGKG 82

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: 39.97 E-value: 6.18e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848  425 VVIECKPKASPRPVYTW-RKGREI-LRENERITISEDGNLRIINVT---KSDA--GSYTCIATNHFGTASSTgNVVVK 495
Cdd:cd05874     19 IVIQCEAKGKPPPSFSWtRNGTHFdIDKDPKVTMKPNTGTLVINIMngeKAEAyeGVYQCTARNERGAAVSN-NIVIR 95

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: 39.23 E-value: 6.19e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  141 VLLC---GPPPhsgeLSYAWIFNEHP--SYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNTVT 201
Cdd:cd00096      2 TLTCsasGNPP----PTITWYKNGKPlpPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

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: 39.79 E-value: 6.58e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848  132 VSVRRGQGMVLLC----GPPPhsgelSYAWIFNEHPSYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNT 199
Cdd:cd20952      9 QTVAVGGTVVLNCqatgEPVP-----TISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL 75

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: 39.50 E-value: 7.83e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDI--GMDFRYSVVEgslLINnpnkTQDSGTYQCIATNSFGTI 109
Cdd:cd05739     15 VNLTCVAVGAPMPYVKWMKGGEELTKedEMPVGRNVLE---LTN----IYESANYTCVAISSLGMI 73

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: 39.55 E-value: 8.20e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   44 KKVKLSCEVKGNPKPHIRWKLNGTDV------DIGMDFRYSVVE-GSLLINNPNKTqDSGTYQCIATNSFGTIVSReakl 116
Cdd:cd05726     15 RTVTFQCETKGNPQPAIFWQKEGSQNllfpyqPPQPSSRFSVSPtGDLTITNVQRS-DVGYYICQALNVAGSILAK---- 89


                   ....*.
gi 1958767848  117 qfAYLE 122
Cdd:cd05726     90 --AQLE 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: 39.45 E-value: 8.20e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  327 VAMEESVFWECKANGRPKPTYRWLKNGDpllTRERIQIEQGTL--NITIVN----------LSDAGMYQCVAENKHGVIY 394
Cdd:cd05765     12 VKVGETASFHCDVTGRPQPEITWEKQVP---GKENLIMRPNHVrgNVVVTNigqlviynaqPQDAGLYTCTARNSGGLLR 88


                   ....*..
gi 1958767848  395 ASAELSV 401
Cdd:cd05765     89 ANFPLSV 95

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: 39.40 E-value: 8.75e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  419 VKVGGEVVIECKP-KASPRPVYTWRKGR-EILRENERITISEDGNLRIINVTKSDAGS-YTCIATNHFgtassTGNVVVK 495
Cdd:cd05845      9 VEEGDPVVLPCNPpKGAPPPRIYWMNSSlEHITQDERVSMGQNGDLYFSNVMEQDSHPdYICHAHFPG-----TRTIVQK 83


                   ....*..
gi 1958767848  496 DPTKVMV 502
Cdd:cd05845     84 EPITLKV 90

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: 39.48 E-value: 9.22e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958767848  336 ECKANGRPKPT-YRWLKNGDPLLTRER--IQIE-QGTLNITIVNLSDAGMYQCVAENKHGV 392
Cdd:cd20979     21 ECVTEGGDQGVkYSWLKDGKSFNWQEHnvAQRKdEGSLVFLKPQASDEGQYQCFAETPAGV 81

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: 39.13 E-value: 9.25e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   900 PSQPPGNIIWNSSDSKIILNWDQVKALDNESEVKGYKVLYRWNRQSSTSVIET-NKTSVELS-LPFDEDYIIEIKPFSDG 977
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTpSSTSYTLTgLKPGTEYEFRVRAVNGA 80


                    ...
gi 1958767848   978 GDG 980
Cdd:smart00060   81 GEG 83

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); 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. 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: 409451 Cd Length: 97 Bit Score: 39.64 E-value: 9.46e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  327 VAMEESVFWECKANGRPKPT-YRWLK-NGDPLL-TRERIQI-----EQGTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd05865     12 ISVGESKFFLCQVAGEAKDKdISWFSpNGEKLTpNQQRISVvrnddYSSTLTIYNANIDDAGIYKCVVSNEDE 84

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: 39.23 E-value: 1.02e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  432 KASPRPVYTWRKGREILRENERItISEDGNLRIINVTKSDAGSYTCIAT-NHFGTA---SSTGNVVVKD 496
Cdd:cd05757     25 NENVLPPIQWYKDCKPLQGDKRF-IPKGSKLLIQNVTEEDAGNYTCKFTyTHNGKQynvTRTISLTVTE 92

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

Pssm-ID: 409378 Cd Length: 114 Bit Score: 39.87 E-value: 1.04e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  418 LVKVGGEVVIECK--PKASP-------------RPVYTWRKGREILREN-----ERITISEDGN------LRIINVTKSD 471
Cdd:cd05713     11 LALVGEDAELPCHlsPKMSAehmevrwfrsqfsPVVHLYRDGQDQEEEQmpeyrGRTELLKDAIaegsvaLRIHNVRPSD 90


                   ....*.
gi 1958767848  472 AGSYTC 477
Cdd:cd05713     91 EGQYTC 96

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: 39.43 E-value: 1.05e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  314 AQPNWVQIINDihVAME-ESVFWECKANGRPKPTYRWLKNGDPLLTRE---------RIQIEQGTLNITIVNLSDAGMYQ 383
Cdd:cd05732      1 VQPKITYLENQ--TAVElEQITLTCEAEGDPIPEITWRRATRGISFEEgdldgrivvRGHARVSSLTLKDVQLTDAGRYD 78

                           90
                   ....*....|....*...
gi 1958767848  384 CVAENKHGVIYASAELSV 401
Cdd:cd05732     79 CEASNRIGGDQQSMYLEV 96

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: 38.72 E-value: 1.09e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848   45 KVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVE--GSLLINNPNKtQDSGTYQCIATNSFGT 108
Cdd:cd05748      9 SLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTAssTSLVIKNAKR-SDSGKYTLTLKNSAGE 73

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: 39.10 E-value: 1.09e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  337 CKAN-GRPKPTYRWLKNGDPLLTRERIQI---EQGTLNITIVNLS--DAGMYQCVAENKHGVIYASAEL 399
Cdd:pfam00047   18 CSAStGSPGPDVTWSKEGGTLIESLKVKHdngRTTQSSLLISNVTkeDAGTYTCVVNNPGGSATLSTSL 86

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: 38.70 E-value: 1.26e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  331 ESVFWECKANGRPKPTYRWLKNGDPL-LTRERIQIEQGTLNITIVNL-SDAGMYQCVAENKHGVIyASAELSV 401
Cdd:cd20958     16 QTLRLHCPVAGYPISSITWEKDGRRLpLNHRQRVFPNGTLVIENVQRsSDEGEYTCTARNQQGQS-ASRSVFV 87

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: 38.73 E-value: 1.40e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADgKPIARKAR-----RHKSSGILEIPNFQQEDAGSYECVAENSRGKNia 306
Cdd:cd05737      8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKND-QALAFLDHcnlkvEAGRTVYFTINGVSSEDSGKYGLVVKNKYGSE-- 84


                   ....*
gi 1958767848  307 KGQVT 311
Cdd:cd05737     85 TSDVT 89

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: 39.17 E-value: 1.52e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   46 VKLSCEVKGNPKPHIRW----KLNGTDVdiGMD-FRYSVVEGSLLINNPNKT-----------QDSGTYQCIATNSFG 107
Cdd:cd05858     19 AEFVCKVYSDAQPHIQWlkhvEKNGSKY--GPDgLPYVEVLKTAGVNTTDKEievlylrnvtfEDAGEYTCLAGNSIG 94

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: 38.78 E-value: 1.60e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  230 QFPETVPAEKGSTVKLECFALGNPVPTILWRRADGKP---IARKAR----RHKSSGILEIPNFQQEDAGSYECVAE-NSR 301
Cdd:cd16096      3 QHPRFAAKKRSSMVKFHCYTNYSGVMTWFRKKGNQRPqelFPEDGRisqtQNGSVYTLTIQNIQYEDNGIYFCQQKcNST 82


                   ....*..
gi 1958767848  302 GKNIAKG 308
Cdd:cd16096     83 EPDVTDG 89

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: 38.81 E-value: 1.75e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  314 AQPNWVQIINDIHVAMEESVFWECKANGRPKPTYRWlKNGDPLLTRE----------RIQIEQGTLNITIVNLSDAGMYQ 383
Cdd:cd05869      1 AKPKITYVENQTAMELEEQITLTCEASGDPIPSITW-RTSTRNISSEektldghivvRSHARVSSLTLKYIQYTDAGEYL 79

                           90
                   ....*....|....*...
gi 1958767848  384 CVAENKHGVIYASAELSV 401
Cdd:cd05869     80 CTASNTIGQDSQSMYLEV 97

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: 38.33 E-value: 1.78e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVPTILWRRADGKPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRGKNIAKGQV 310
Cdd:cd05723      4 PSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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: 409559 Cd Length: 82 Bit Score: 38.38 E-value: 1.79e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958767848  348 RWLKNGDPLLTRERIQIEQG----TLNITIVNLSDAGMYQCVA 386
Cdd:cd20967     29 KWYKDGQELQSSSKVIFESIgakrTLTVQQASLADAGEYQCVA 71

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: 1.85e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  332 SVFWECKANGrPKPTYRWL--KNGDP----LLTRERI-QIEQGTLnITIVNLSDAGMYQCVAEnKHGviyasaelsviae 404
Cdd:cd05871     14 STFLECLPKS-PQATVKWLfqRGGDQrkeeVKSEERLiVTDRGLL-LRSLQRSDAGVYTCQAV-EHG------------- 77

                           90
                   ....*....|
gi 1958767848  405 spdFSRTLLK 414
Cdd:cd05871     78 ---FSQTLVK 84

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: 38.63 E-value: 2.03e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  225 PKIEVQFPETVPAEKGSTVKLECFALGNPVP-TILWRRaDGKPI-----ARKARRHKSSGILEIPNFQQEDAGSYECVAE 298
Cdd:cd20959      2 PRIIPFAFGEGAAQVGMRAQLHCGVPGGDLPlNIRWTL-DGQPIsddlgITVSRLGRRSSILSIDSLEASHAGNYTCHAR 80


                   ....
gi 1958767848  299 NSRG 302
Cdd:cd20959     81 NSAG 84

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: 38.42 E-value: 2.04e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  235 VPAEKGSTVKLECFALGNPVPTILWRRA---------DGKPIAR---KARRHKSSgiLEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05870     11 ETTVENGAATLSCKAEGEPIPEITWKRAsdghtfsegDKSPDGRievKGQHGESS--LHIKDVKLSDSGRYDCEAASRIG 88

Immunoglobulin (Ig)-like domain of platelet-derived growth factor (PDGF) receptors (R), alpha and beta; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of platelet-derived growth factor (PDGF) receptors (R), alpha (also known as cluster of differentiation (CD) 140a), and beta (also known as CD140b). PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFRalpha binds to all three PDGFs, whereas the PDGFRbeta binds only to PDGF-B. PDGFRs alpha and beta have similar organization: an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFRalpha and PDGFRbeta are essential for normal development.

Pssm-ID: 409447 Cd Length: 99 Bit Score: 38.35 E-value: 2.22e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  227 IEVQFPETVpAEKGSTVKLECFALGNPVPTILW---RRADGKPIAR----KARRHKSSGILEIPNFQQEDAGSYECVAEN 299
Cdd:cd05861      5 VEMEAVKTV-VRQGETITLMCIVIGNEVVDLEWtypGKESGRGIEPveefKVPPYHLVYTLTIPSATLEDSGTYECAVTE 83


                   .
gi 1958767848  300 S 300
Cdd:cd05861     84 A 84

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: 2.28e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  231 FPETVPAekGSTVKLECFALGNPVPTILW-RRADGKPIARKARRH-------KSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05765      8 THQTVKV--GETASFHCDVTGRPQPEITWeKQVPGKENLIMRPNHvrgnvvvTNIGQLVIYNAQPQDAGLYTCTARNSGG 85

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: 38.25 E-value: 2.43e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  504 PSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGHLIDFDKDGDHFERVGGDSAgdLMIRNIQLKHAGKYVCMVQTSVDK 583
Cdd:cd05744      7 PGDLEVQEGRLCRFDCKVSGLPTPDL--FWQLNGKPVRPDSAHKMLVRENGRHS--LIIEPVTKRDAGIYTCIARNRAGE 82


                   ....*....
gi 1958767848  584 LSAAADLIV 592
Cdd:cd05744     83 NSFNAELVV 91

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: 37.94 E-value: 2.44e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848   41 SEEKKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSVVEG---SLLINNPNkTQDSGTYQCIATNSFG 107
Cdd:cd20973     10 VEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDglcSLIISDVC-GDDSGKYTCKAVNSLG 78

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: 38.45 E-value: 2.56e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  419 VKVGGEVVIEC-KPKASPRPVYTWRKGREILRENERITIS----------EDGNLRIINVTKSDAGSYTCIATNHFGTA 486
Cdd:cd20950      9 ATIGNRAVLTCsEPDGSPPSEYTWFKDGVVMPTNPKSTRAfsnssysldpTTGELVFDPLSASDTGEYSCEARNGYGTP 87

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: 38.07 E-value: 2.78e-03

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1958767848  166 QDNRRFVSQETgNLYIAKVEKADVGNYTCVVTNT 199
Cdd:cd05757     42 QGDKRFIPKGS-KLLIQNVTEEDAGNYTCKFTYT 74

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: 38.59 E-value: 2.85e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  415 RVTLVKVGGEVVIECKPKASP-------------------RPVYTWRKGREILRENERITISE-----DGNLRIINVTKS 470
Cdd:pfam07686    4 REVTVALGGSVTLPCTYSSSMseastsvywyrqppgkgptFLIAYYSNGSEEGVKKGRFSGRGdpsngDGSLTIQNLTLS 83


                   ....*..
gi 1958767848  471 DAGSYTC 477
Cdd:pfam07686   84 DSGTYTC 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: 38.06 E-value: 2.89e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848   46 VKLSCEVKGNPKPHIRWK-LNGTDVDIGMDFRYS-----VVEGSLLINNPNKTqDSGTYQCIATNSFGTIVSR 112
Cdd:cd20954     19 VMLHCQADGFPTPTVTWKkATGSTPGEYKDLLYDpnvriLPNGTLVFGHVQKE-NEGHYLCEAKNGIGSGLSK 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 37.62 E-value: 3.09e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  132 VSVRRGQGMVLLC---G-PPPhsgelSYAWIFNEHPSYQDNRRFVSQETGN--LYIAKVEKADVGNYTCVVTNTV 200
Cdd:pfam07679   10 VEVQEGESARFTCtvtGtPDP-----EVSWFKDGQPLRSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVATNSA 79

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: 37.86 E-value: 3.14e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958767848   46 VKLSCEV-KGNPKPHIRWKLNGTDV--DIGMDFRYSVVEGSLLINNPNKTQDSGTYQCIATNSFGTI 109
Cdd:cd20959     20 AQLHCGVpGGDLPLNIRWTLDGQPIsdDLGITVSRLGRRSSILSIDSLEASHAGNYTCHARNSAGSA 86

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: 37.72 E-value: 3.24e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGD--PLLTRERIQIE----QGTLNITIVNLSDAGMYQCVAENK 389
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQviSTSTLPGVQISfsdgRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|..
gi 1958767848  390 HGVIYASAELSV 401
Cdd:cd20974     81 SGQATSTAELLV 92

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: 37.99 E-value: 3.39e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDIGmDFRYSVVEGS--LLINNPNKtQDSGTYQCIATNSFG 107
Cdd:cd05730     21 VTLACDADGFPEPTMTWTKDGEPIESG-EEKYSFNEDGseMTILDVDK-LDEAEYTCIAENKAG 82

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: 37.85 E-value: 3.50e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958767848   44 KKVKLSCEVKGNPKPHIRWKLNGTDVDIGMDFRYSV--------VEGSLLINnPNKTQDSGTYQCIATNSFG 107
Cdd:cd05735     19 QKKEMSCTAHGEKPIIVRWEKEDTIINPSEMSRYLVttkevgdeVISTLQIL-PTVREDSGFFSCHAINSYG 89

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.49 E-value: 3.66e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958767848  415 RVTLVKVGGEVVIECKPKASPRPVYtWR-KGREILRENERITISEDGnLRIINVTKSDAGSYTCIA 479
Cdd:cd05873      4 RQRTFKLGGNAELKCSPKSNLARVV-WKfQGKVLKAESPKYGLYGDG-LLIFNASEADAGRYQCLS 67

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: 37.51 E-value: 3.75e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  497 PTKVMVPPSSMDVTVGESIVLPCQVThdhsldivftwTFNGHLIDFDKDGDHF---ERVGGDSAGDLMIRNIQLKHAGKY 573
Cdd:cd20957      1 PLSATIDPPVQTVDFGRTAVFNCSVT-----------GNPIHTVLWMKDGKPLghsSRVQILSEDVLVIPSVKREDKGMY 69

                           90
                   ....*....|....*..
gi 1958767848  574 VCMVQTSVDKLSAAADL 590
Cdd:cd20957     70 QCFVRNDGDSAQATAEL 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.37 E-value: 3.82e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  128 TRSTVSVRRGQGMVLLC---GPPPhsgeLSYAWifnehpsYQDNRrfVSQETGNLYIAKVEKADVGNYTCVVTNTVTSHQ 204
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCsapGNPP----PSYTW-------YKDGS--AISSSPNFFTLSVSAEDSGTYTCVARNGRGGKV 71

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: 37.60 E-value: 3.86e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  425 VVIECKPKASPRPVYTW-RKGREILRENERITIS-EDGNLRIINVTKSDAGSYTCIATNHFGTASSTGN 491
Cdd:cd05760     19 VTLRCHIDGHPRPTYQWfRDGTPLSDGQGNYSVSsKERTLTLRSAGPDDSGLYYCCAHNAFGSVCSSQN 87

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: 37.61 E-value: 3.99e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  126 TRTRSTVSVRRGQGMVLLC----GPPPhsgelSYAWIfNEHPSYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNTVT 201
Cdd:cd20968      3 TRPPTNVTIIEGLKAVLPCttmgNPKP-----SVSWI-KGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76


                   .
gi 1958767848  202 S 202
Cdd:cd20968     77 I 77

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: 37.56 E-value: 4.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  128 TRSTVSVRRGQGMVLLCGPPPHSGELSYAWIFN---EHPSYQDNRRFVSQETGNLYIAKVEKADVGNYTCVVTNTVTSHQ 204
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSASTGSPGPDVTWSKEggtLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81

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: 37.37 E-value: 4.05e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958767848  497 PTKVMVPPSSMDVTVGESIVLPCQVTHDHSLDIvfTWTFNGHLIDFDKDGDHFERvggdsaGDLMIRNIQLKHAGKYVC 575
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKI--TWLHNGKPLQGPMERATVED------GTLTIINVQPEDTGYYGC 71

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: 38.08 E-value: 4.08e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  500 VMVPPSSMDVTVGESIVLPCQVTHDHSLDIVFtW----------------TFNGHLIDFDKDGDHFERVGGDSAgDLMIR 563
Cdd:cd00099      1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTYIY-WyrqkpgqgpefliylsSSKGKTKGGVPGRFSGSRDGTSSF-SLTIS 78

                           90
                   ....*....|....*..
gi 1958767848  564 NIQLKHAGKYVCMVQTS 580
Cdd:cd00099     79 NLQPEDSGTYYCAVSES 95

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 37.63 E-value: 4.31e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  316 PNWVQIINDIHVAMEESVFWECKANGRPKPTYRWLKNGDPLLTRERIQIEQ----GTLNITIVNLSDAGMYQCVAENKHG 391
Cdd:cd05762      2 PQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIENtensSKLTITEGQQEHCGCYTLEVENKLG 81

                           90
                   ....*....|....*.
gi 1958767848  392 VIYASAELSVIaESPD 407
Cdd:cd05762     82 SRQAQVNLTVV-DKPD 96

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: 37.47 E-value: 4.52e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958767848  132 VSVRRGQGMVLLCGPPPHSGELSYAWIFNE-HPSYQDNRRFVSQEtGNLYIAKVEKADVGN-YTC 194
Cdd:cd05845      7 VEVEEGDPVVLPCNPPKGAPPPRIYWMNSSlEHITQDERVSMGQN-GDLYFSNVMEQDSHPdYIC 70

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: 37.15 E-value: 4.93e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  503 PPSSMDVTVGESIVLPCQVThdhSLDIVFT--WTfnghlidfdkdgdhfeRVGG-------DSAGDLMIRNIQLKHAGKY 573
Cdd:cd05754      7 EPRSQEVRPGADVSFICRAK---SKSPAYTlvWT----------------RVNGtlpsramDFNGILTIRNVQLSDAGTY 67

                           90
                   ....*....|....*...
gi 1958767848  574 VCMVQTSVDKLSAAADLI 591
Cdd:cd05754     68 VCTGSNMLDTDEATATLY 85

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: 4.94e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  232 PETVPAEKGSTVKLECFALGNPVP-TILWRRaDGKPIARKArrHKSSGILEIPNFQQedAGSYECVAENSRGKNIAK-GQ 309
Cdd:cd05749      6 PEDLAVTANTPFNLTCQAVGPPEPvEILWWQ-GGSPLGGPP--APSPSVLNVPGLNE--TTKFSCEAHNAKGLTSSRtAT 80


                   ..
gi 1958767848  310 VT 311
Cdd:cd05749     81 VT 82

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: 37.06 E-value: 5.46e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  229 VQFPETVPAEKGSTVKLECFALGNPVPTILWRRaDGKPIARKARR----HKSSG--ILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd05892      4 IQKPQNKKVLEGDPVRLECQISAIPPPQIFWKK-NNEMLQYNTDRislyQDNCGriCLLIQNANKKDAGWYTVSAVNEAG 82

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: 37.06 E-value: 5.59e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   44 KKVKLSCEVKGNPKPHIRWKLNGTDVDigMDFRYSVVEGS-----LLINNPNKTQDSGTYQCIATNSFGTIVSREAKL 116
Cdd:cd20971     17 SNATLVCKVTGHPKPIVKWYRQGKEII--ADGLKYRIQEFkggyhQLIIASVTDDDATVYQVRATNQGGSVSGTASLE 92

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: 37.22 E-value: 8.45e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   48 LSCEVKGNPKPHIRWKLNGTDVDIGmDFRYS-------VVEGSLL-INNPNKTQDSGTYQCIATNSFG 107
Cdd:cd05773     28 LVCQAQGVPRVQFRWAKNGVPLDLG-NPRYEettehtgTVHTSILtIINVSAALDYALFTCTAHNSLG 94

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: 36.31 E-value: 8.52e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958767848   46 VKLSCEVKGNPKPHIRWKLNGTDVDIGMdfRYSVVE----GSLLINNPnKTQDSGTYQCIATNSFGTI 109
Cdd:cd05743      4 VEFTCVATGVPTPIINWRLNWGHVPDSA--RVSITSeggyGTLTIRDV-KESDQGAYTCEAINTRGMV 68

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second 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: 409392 Cd Length: 88 Bit Score: 36.39 E-value: 8.66e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958767848  419 VKVGGEVVIECKPKAS-PRPVYTWRKGR--EILRENERITISED-GNLRIINVTKSDAGSYTCIATNHFGTAS 487
Cdd:cd05727      7 VKEGWGVVLFCDPPPHyPDLSYRWLLNEfpNFIPEDGRRFVSQTnGNLYIAKVEASDRGNYSCFVSSPSSTKS 79

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: 36.75 E-value: 9.82e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958767848  238 EKGSTVKLECFALGNPVPTILWRR-ADG----KPIARKARRHKSSGILEIPNFQQEDAGSYECVAENSRG 302
Cdd:cd20953     16 SSASSIALLCPAQGYPAPSFRWYKfIEGttrkQAVVLNDRVKQVSGTLIIKDAVVEDSGKYLCVVNNSVG 85