First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908  36 VTIELLPSQVVEGEDVLFLVNNLPGNLTAFAWFKGRTNRK-HGIALYAVASDLYV----HSDRETLYNNGSLMIHNVTQK 110
Cdd:cd05774   1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPnFLIASYIISTNSSTpgpaYSGRETIYPNGSLLIQNVTQK 80

                        90       100
                ....*....|....*....|....*.
gi 74959908 111 DRGYYTLRTFNKHAETVSTTFtFLHV 136
Cdd:cd05774  81 DTGFYTLQTITADLQTEQASV-HLQV 105

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74959908 382 QPFVQI-TDTTANAQRSLTFTCVTPDIATSILWFFNSHSLKPTERITLSPTKCGLRIDDVRSEDAGNYQCVVVN 454
Cdd:cd05740   1 KPFISSnNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908  36 VTIELLPSQVVEGEDVLFLVNNLPGNLTAFAWFKGRTNRK-HGIALYAVASDLYV----HSDRETLYNNGSLMIHNVTQK 110
Cdd:cd05774   1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPnFLIASYIISTNSSTpgpaYSGRETIYPNGSLLIQNVTQK 80

                        90       100
                ....*....|....*....|....*.
gi 74959908 111 DRGYYTLRTFNKHAETVSTTFtFLHV 136
Cdd:cd05774  81 DTGFYTLQTITADLQTEQASV-HLQV 105

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74959908 382 QPFVQI-TDTTANAQRSLTFTCVTPDIATSILWFFNSHSLKPTERITLSPTKCGLRIDDVRSEDAGNYQCVVVN 454
Cdd:cd05740   1 KPFISSnNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908   384 FVQ-ITDTTANAQRSLTFTCV---TPDIatSILWFFNSHSLKPTERITLSPT--KCGLRIDDVRSEDAGNYQCVVVNRNG 457
Cdd:pfam07679   3 FTQkPKDVEVQEGESARFTCTvtgTPDP--EVSWFKDGQPLRSSDRFKVTYEggTYTLTISNVQPDDSGKYTCVATNSAG 80

                  ....*
gi 74959908   458 DAKAS 462
Cdd:pfam07679  81 EAEAS 85

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908   277 VPRY--VAEGESVLLLVHNLP---EELISFTWYnsmyRVPA-----FKIVEFNVIRNITTWGDVYRGR-DTVYANGSLML 345
Cdd:pfam07686   2 TPREvtVALGGSVTLPCTYSSsmsEASTSVYWY----RQPPgkgptFLIAYYSNGSEEGVKKGRFSGRgDPSNGDGSLTI 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 74959908   346 QDVTEEDARMYTLETLNVNYTVERAHVQFYV 376
Cdd:pfam07686  78 QNLTLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 74959908    209 PAYSGREKLDSNG---SLRIENVTQKDAGLYTLRVlGTDMKSEEAHVELQV 256
Cdd:smart00410  36 LAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAA-TNSSGSASSGTTLTV 85

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908  36 VTIELLPSQVVEGEDVLFLVNNLPGNLTAFAWFKGRTNRK-HGIALYAVASDLYV----HSDRETLYNNGSLMIHNVTQK 110
Cdd:cd05774   1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPnFLIASYIISTNSSTpgpaYSGRETIYPNGSLLIQNVTQK 80

                        90       100
                ....*....|....*....|....*.
gi 74959908 111 DRGYYTLRTFNKHAETVSTTFtFLHV 136
Cdd:cd05774  81 DTGFYTLQTITADLQTEQASV-HLQV 105

Immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and related 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. 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. This family corresponds to the D1 Ig-like domain. Also belonging to this group is the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family, CD84-like family. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. SLAM family proteins are organized as an extracellular domain with having two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908 161 VTEGQHVILHVYNIPENLQGFIWFKGMTVHRHLEIGRYTIGRKSSVFGPAYSGREKLDSNGSLRIENVTQKDAGLYTLRV 240
Cdd:cd05741   7 GAEGKNVLLLVPNLQTPLKSVSWYKGKQVSRNDEIAEYENSSDEFRAGSAFSGREYIYTNGSLLIQNITLSDTGFYTLES 86

                        90
                ....*....|....*.
gi 74959908 241 LGTDMKSEEAHVELQV 256
Cdd:cd05741  87 TNIGGKTESATFQLHV 102

Immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and related 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. 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. This family corresponds to the D1 Ig-like domain. Also belonging to this group is the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family, CD84-like family. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. SLAM family proteins are organized as an extracellular domain with having two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908  44 QVVEGEDVLFLVNNLPGNLTAFAWFKG-RTNRKHGIALYAVASDLY----VHSDRETLYNNGSLMIHNVTQKDRGYYTLR 118
Cdd:cd05741   6 YGAEGKNVLLLVPNLQTPLKSVSWYKGkQVSRNDEIAEYENSSDEFragsAFSGREYIYTNGSLLIQNITLSDTGFYTLE 85

                        90
                ....*....|....*...
gi 74959908 119 TFNKHAETVSTTFtFLHV 136
Cdd:cd05741  86 STNIGGKTESATF-QLHV 102

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908   161 VTEGQHVILHV---YNIPENLQGFIWFKGMTVHRH-LEIGRYTIGRKSSVFGPAYSGREKLD-SNGSLRIENVTQKDAGL 235
Cdd:pfam07686   8 VALGGSVTLPCtysSSMSEASTSVYWYRQPPGKGPtFLIAYYSNGSEEGVKKGRFSGRGDPSnGDGSLTIQNLTLSDSGT 87

                          90       100
                  ....*....|....*....|.
gi 74959908   236 YTLRVLGTDMKSEEAHVELQV 256
Cdd:pfam07686  88 YTCAVIPSGEGVFGKGTRLTV 108

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74959908    389 DTTANAQRSLTFTC-VTPDIATSILWFFNSHS-LKPTERITLS--PTKCGLRIDDVRSEDAGNYQCVVVNRNGDAKAS 462
Cdd:smart00410   3 SVTVKEGESVTLSCeASGSPPPEVTWYKQGGKlLAESGRFSVSrsGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74959908 398 LTFTC-VTPDIATSILWFFNSHSLKPT--ERITLSPTKCGLRIDDVRSEDAGNYQCVVVNRNG 457
Cdd:cd00096   1 VTLTCsASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908 382 QPFVQitdtTANAQRSLTFTC-VTPDIATSILWFFNSHSLKPTERITLSPTKCgLRIDDVRSEDAGNYQCVVVNRNGDAK 460
Cdd:cd20957   7 DPPVQ----TVDFGRTAVFNCsVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDGDSAQ 81

                ....*.
gi 74959908 461 ASHPIR 466
Cdd:cd20957  82 ATAELK 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 74959908   385 VQITDTTANAQRSLTFTC-VTPDIATSILWFFNSHSLKP--TERITLSPTKCGLRIDDVRSEDAGNYQCVVVN 454
Cdd:pfam13927   6 VSPSSVTVREGETVTLTCeATGSPPPTITWYKNGEPISSgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908  46 VEGEDVLFLVNNLPGNLTAFAWFKGRTN-----RKHGIALYAVASDlYVHSDretlYNNGSLMIHNVTQKDRGYYTLRTF 120
Cdd:cd05775   8 ALGGNVTLTISSLQDDIDEIKWKKTKDKiveweNNIGPTYFGSFKD-RVLLD----KESGSLTIKNLTKEDSGTYELEIT 82

                        90
                ....*....|....*.
gi 74959908 121 NKHAETVSTTFTfLHV 136
Cdd:cd05775  83 STNGKVLSSKFT-LEV 97

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 74959908 410 SILWFFNSHSLKPTERITLSPTKcGLRIDDVRSEDAGNYQCVVVNRNGDAKAS 462
Cdd:cd04969  33 TISWSKGTELLTNSSRICILPDG-SLKIKNVTKSDEGKYTCFAVNFFGKANST 84

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908 381 TQPFVQITDTTANAQRsltFTCVT---PDiaTSILWFFNSHSLKPTERITL---SPTKCGLRIDDVRSEDAGNYQCVVVN 454
Cdd:cd20973   1 IQTLRDKEVVEGSAAR---FDCKVegyPD--PEVKWMKDDNPIVESRRFQIdqdEDGLCSLIISDVCGDDSGKYTCKAVN 75

                ....*...
gi 74959908 455 RNGDAKAS 462
Cdd:cd20973  76 SLGEATCS 83

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 74959908   397 SLTFTC--VTPDIATSILWFFNSHSLKPTERITLSPTKCG---LRIDDVRSEDAGNYQCVVVNRNG 457
Cdd:pfam00047  13 SATLTCsaSTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTqssLLISNVTKEDAGTYTCVVNNPGG 78

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 74959908 396 RSLTFTC-VTPDIATSILWFFNSHSLKPTERITLSPTKCG---LRIDDVRSEDAGNYQCVVVNRNGDAKAS 462
Cdd:cd05744  16 RLCRFDCkVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGrhsLIIEPVTKRDAGIYTCIARNRAGENSFN 86

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 74959908 413 WFFNSHSLKPTE----RITLSPTKCGLRIDDVRSEDAGNYQCVVVNRNGDAKAS 462
Cdd:cd05750  34 WFKDGKELNRKRpkniKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVT 87

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 74959908 389 DTTANAQRSLTFTC-VTPDIATSILWFFNSHSLkPTERITLSPTKcGLRIDDVRSEDAGNYQCVVVNRNGDAKAS 462
Cdd:cd05725   6 NQVVLVDDSAEFQCeVGGDPVPTVRWRKEDGEL-PKGRYEILDDH-SLKIRKVTAGDMGSYTCVAENMVGKIEAS 78

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 74959908    209 PAYSGREKLDSNG---SLRIENVTQKDAGLYTLRVlGTDMKSEEAHVELQV 256
Cdd:smart00410  36 LAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAA-TNSSGSASSGTTLTV 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 74959908 410 SILWFFNSHSLKPTERITLSPTKcGLRIDDVRSEDAGNYQCVVVNRNGDA 459
Cdd:cd20968  30 SVSWIKGDDLIKENNRIAVLESG-SLRIHNVQKEDAGQYRCVAKNSLGIA 78

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74959908 383 PFV-QITDTTANAQRSLTFTCvtPDIA---TSILWFFNSHSLKPTERITLSPTkcG-LRIDDV-RSEDAGNYQCVVVNRN 456
Cdd:cd20958   2 PFIrPMGNLTAVAGQTLRLHC--PVAGypiSSITWEKDGRRLPLNHRQRVFPN--GtLVIENVqRSSDEGEYTCTARNQQ 77

                .
gi 74959908 457 G 457
Cdd:cd20958  78 G 78