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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090  69 KPSIAVSPGTAIEQKDMVTFYCTTKDVNITIHWVSNNLSIVFHERMQLSKDGKILTILIVQREDSGTYQCEARDALLSQR 148
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 584277090 149 SDPIFLDV 156
Cdd:cd05740   81 SDPVTLDV 88

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090  69 KPSIAVSPGTAIEQKDMVTFYCTTKDVNITIHWVSNNLSIVFHERMQLSKDGKILTILIVQREDSGTYQCEARDALLSQR 148
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 584277090 149 SDPIFLDV 156
Cdd:cd05740   81 SDPVTLDV 88

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 584277090    70 PSIAVSPGtaieqkDMVTFYCTTK-DVNITIHWVSNNLSIVFH-ERMQLSKDGKILTILI--VQREDSGTYQCEARDA 143
Cdd:smart00410   2 PSVTVKEG------ESVTLSCEASgSPPPEVTWYKQGGKLLAEsGRFSVSRSGSTSTLTIsnVTPEDSGTYTCAATNS 73

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 584277090   69 KPSIAVSPG-TAIEQKDMVTFYCTTKDVNI-TIHWVSNNLSI--VFHERMQLSKDGKILTILIVQREDSGTYQCEAR 141
Cdd:pfam13927   1 KPVITVSPSsVTVREGETVTLTCEATGSPPpTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 584277090   271 SVDLTCQ-TVNQSVNVQWFLSG-QPLLPSEHLQLSADNR--TLIIHGLQRNDTGPYACEVWNwGSRARSEPLELTI 342
Cdd:smart00410  11 SVTLSCEaSGSPPPEVTWYKQGgKLLAESGRFSVSRSGStsTLTISNVTPEDSGTYTCAATN-SSGSASSGTTLTV 85

IL-1 receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090 217 IHAVSREHEGLYRCLVSNSatHLSSLGTLKVRVLETLTMPQVvpsslnlvENARSVDLTC------QTVNQSVNVQWFLS 290
Cdd:PHA02826 102 IGNVINIDEGIYICTISSG--NICEESTIRLTFDSGTINYQF--------NSGKDSKLHCygtdgiSSTFKDYTLTWYKN 171

                         90       100       110
                 ....*....|....*....|....*....|....
gi 584277090 291 GQPLLPSEHLQLSADNRTLIIHGLQRNDTGPYAC 324
Cdd:PHA02826 172 GNIVLYTDRIQLRNNNSTLVIKSATHDDSGIYTC 205

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090  69 KPSIAVSPGTAIEQKDMVTFYCTTKDVNITIHWVSNNLSIVFHERMQLSKDGKILTILIVQREDSGTYQCEARDALLSQR 148
Cdd:cd05740    1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 584277090 149 SDPIFLDV 156
Cdd:cd05740   81 SDPVTLDV 88

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 584277090    70 PSIAVSPGtaieqkDMVTFYCTTK-DVNITIHWVSNNLSIVFH-ERMQLSKDGKILTILI--VQREDSGTYQCEARDA 143
Cdd:smart00410   2 PSVTVKEG------ESVTLSCEASgSPPPEVTWYKQGGKLLAEsGRFSVSRSGSTSTLTIsnVTPEDSGTYTCAATNS 73

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 584277090   69 KPSIAVSPG-TAIEQKDMVTFYCTTKDVNI-TIHWVSNNLSI--VFHERMQLSKDGKILTILIVQREDSGTYQCEAR 141
Cdd:pfam13927   1 KPVITVSPSsVTVREGETVTLTCEATGSPPpTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 584277090  171 VASGEVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSILSH----------TTRTFTIHAVSREHEGLYRCLVSN 234
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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 584277090 272 VDLTCQTV-NQSVNVQWFLSGQPLLPSEHL--QLSADNRTLIIHGLQRNDTGPYACEVWNWGSRARS 335
Cdd:cd00096    1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090   69 KPSIAVSPgTAIEQKDMVTFYCTTK-DVNITIHWVSNNLSIvfhermqlsKDGKILTILIVQREDSGTYQCEARDALLSQ 147
Cdd:pfam13895   1 KPVLTPSP-TVVTEGEPVTLTCSAPgNPPPSYTWYKDGSAI---------SSSPNFFTLSVSAEDSGTYTCVARNGRGGK 70

                  ....*....
gi 584277090  148 RSDPIFLDV 156
Cdd:pfam13895  71 VSNPVELTV 79

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
                 ....*....|....*....|....*....|....*....|....*.
gi 584277090 284 NVQWFLSGQPLlPSEHLQLSADNRTLIIHGLQRN-DTGPYACEVWN 328
Cdd:cd20958   31 SITWEKDGRRL-PLNHRQRVFPNGTLVIENVQRSsDEGEYTCTARN 75

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 584277090 260 PSSLNLVENARSVD------LTCQ-TVNQSVNVQWFLSGQPLLPSEHLQLSADNRtLIIHGLQRNDTGPYACEVWNWGSR 332
Cdd:cd20957    1 PLSATIDPPVQTVDfgrtavFNCSvTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDGDS 79

                 ...
gi 584277090 333 ARS 335
Cdd:cd20957   80 AQA 82

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 584277090 181 EGSSMTFLAETKSHPPCAYTWFLLDSILSHTTRTFtIHAVSREHEGLYRCLVSNSATHLSSLGTLKVRV 249
Cdd:cd20948    9 SGENLNLSCHAASNPPAQYSWTINGTFQTSSQELF-LPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 584277090  175 EVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSILShTTRTFTIHAVSREHEGLYRCLVSNSATHLSS 241
Cdd:pfam13895   7 SPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS-SSPNFFTLSVSAEDSGTYTCVARNGRGGKVS 72

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090  98 TIHWVSN-NLSIVFHERMQLSKDGKILTILIVQREDSGTYQCEARDALLSQRSDPIFLDV 156
Cdd:cd20970   33 EISWTRNgNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSVEKRITLQV 92

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090  70 PSIAVSPGtaieqkDMVTFYCTTKDVNIT--IHW-----------------VSNNLSIVFHERMQLSKDGK---ILTILI 127
Cdd:cd00099    6 RSLSVQEG------ESVTLSCEVSSSFSStyIYWyrqkpgqgpefliylssSKGKTKGGVPGRFSGSRDGTssfSLTISN 79

                         90
                 ....*....|....*.
gi 584277090 128 VQREDSGTYQCEARDA 143
Cdd:cd00099   80 LQPEDSGTYYCAVSES 95

IL-1 receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090 217 IHAVSREHEGLYRCLVSNSatHLSSLGTLKVRVLETLTMPQVvpsslnlvENARSVDLTC------QTVNQSVNVQWFLS 290
Cdd:PHA02826 102 IGNVINIDEGIYICTISSG--NICEESTIRLTFDSGTINYQF--------NSGKDSKLHCygtdgiSSTFKDYTLTWYKN 171

                         90       100       110
                 ....*....|....*....|....*....|....
gi 584277090 291 GQPLLPSEHLQLSADNRTLIIHGLQRNDTGPYAC 324
Cdd:PHA02826 172 GNIVLYTDRIQLRNNNSTLVIKSATHDDSGIYTC 205

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 584277090  70 PSIAVSPGTAIEQKDM--VTFYCT-TKDVNITIHWVSNnlSIVFHERMQLSKDGK-ILTILIVQREDSGTYQCEA 140
Cdd:cd20978    1 PKFIQKPEKNVVVKGGqdVTLPCQvTGVPQPKITWLHN--GKPLQGPMERATVEDgTLTIINVQPEDTGYYGCVA 73

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277090 173 SGEVVEVMEGSSMTFLAETKSHPPCAYTWF-------LLDS--ILSHTTRTFTIHAVSREHEGLYRCLVSNSAT-HLSSL 242
Cdd:cd20970    8 PSFTVTAREGENATFMCRAEGSPEPEISWTrngnliiEFNTryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPgSVEKR 87

                 ....*
gi 584277090 243 GTLKV 247
Cdd:cd20970   88 ITLQV 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 584277090 285 VQWFLSGQPLLP-SEHLQLSADNRTLIIHGLQRNDTGPYACEVWN 328
Cdd:cd04978   31 ITWRLNGVPIEPaPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASN 75