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 584277060 256 PQVVPSSLNLVENARSVDLTCQTVNQSVNVQWFLSGQPLLPSEHLQLSADNRTLIIHGLQRNDTGPYACEVWNWGSRARS 335
Cdd:cd05740    2 PFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANRS 81

                 ....*...
gi 584277060 336 EPLELTIN 343
Cdd:cd05740   82 DPVTLDVI 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060   175 EVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSIL-----------SHTTRTFTIHAVSREHEGLYRCLVSNSATHLSSLG 243
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfsvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 584277060   244 TLKV 247
Cdd:smart00410  82 TLTV 85

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 584277060 256 PQVVPSSLNLVENARSVDLTCQTVNQSVNVQWFLSGQPLLPSEHLQLSADNRTLIIHGLQRNDTGPYACEVWNWGSRARS 335
Cdd:cd05740    2 PFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANRS 81

                 ....*...
gi 584277060 336 EPLELTIN 343
Cdd:cd05740   82 DPVTLDVI 89

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 584277060    70 PSIAVSPGtaieqkDMVTFYCTTK-DVNITIHWVSNNLSIVFH-ERMQLSKDGKILTILI--VQREDSGTYQCEARDA 143
Cdd:smart00410   2 PSVTVKEG------ESVTLSCEASgSPPPEVTWYKQGGKLLAEsGRFSVSRSGSTSTLTIsnVTPEDSGTYTCAATNS 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060   175 EVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSIL-----------SHTTRTFTIHAVSREHEGLYRCLVSNSATHLSSLG 243
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfsvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 584277060   244 TLKV 247
Cdd:smart00410  82 TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 584277060  171 VASGEVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSILSH----------TTRTFTIHAVSREHEGLYRCLVSN 234
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgstrsrslsgSNSTLTISNVTRSDAGTYTCVASN 78

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 584277060 181 EGSSMTFLAETKSHPPCAYTWFLLDSILSHTTRTFtIHAVSREHEGLYRCLVSNSATHLSSLGTLKVRV 249
Cdd:cd20948    9 SGENLNLSCHAASNPPAQYSWTINGTFQTSSQELF-LPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

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 584277060 256 PQVVPSSLNLVENARSVDLTCQTVNQSVNVQWFLSGQPLLPSEHLQLSADNRTLIIHGLQRNDTGPYACEVWNWGSRARS 335
Cdd:cd05740    2 PFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANRS 81

                 ....*...
gi 584277060 336 EPLELTIN 343
Cdd:cd05740   82 DPVTLDVI 89

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 584277060    70 PSIAVSPGtaieqkDMVTFYCTTK-DVNITIHWVSNNLSIVFH-ERMQLSKDGKILTILI--VQREDSGTYQCEARDA 143
Cdd:smart00410   2 PSVTVKEG------ESVTLSCEASgSPPPEVTWYKQGGKLLAEsGRFSVSRSGSTSTLTIsnVTPEDSGTYTCAATNS 73

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060   175 EVVEVMEGSSMTFLAETKSHPPCAYTWFLLDSIL-----------SHTTRTFTIHAVSREHEGLYRCLVSNSATHLSSLG 243
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesgrfsvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 584277060   244 TLKV 247
Cdd:smart00410  82 TLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 584277060  271 SVDLTCQTVNQSV-NVQWFLSGQPLLPSEHLQLSADNR--TLIIHGLQRNDTGPYACEVWNWGSRARSEpLELTI 342
Cdd:pfam07679  17 SARFTCTVTGTPDpEVSWFKDGQPLRSSDRFKVTYEGGtyTLTISNVQPDDSGKYTCVATNSAGEAEAS-AELTV 90

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 584277060   271 SVDLTCQ-TVNQSVNVQWFLSG-QPLLPSEHLQLSADNR--TLIIHGLQRNDTGPYACEVWNwGSRARSEPLELTI 342
Cdd:smart00410  11 SVTLSCEaSGSPPPEVTWYKQGgKLLAESGRFSVSRSGStsTLTISNVTPEDSGTYTCAATN-SSGSASSGTTLTV 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060  86 VTFYCTTK-DVNITIHWVSNNLSIVF--HERMQLSKDGKILTILIVQREDSGTYQCEARDALLSQRSDPI 152
Cdd:cd00096    1 VTLTCSASgNPPPTITWYKNGKPLPPssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060  177 VEVMEGSSMTFLAETKSHPPCAYTWFLLDSILSHTTR----------TFTIHAVSREHEGLYRCLVSNSATHLSSLGTLK 246
Cdd:pfam07679  10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkvtyeggtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

                  .
gi 584277060  247 V 247
Cdd:pfam07679  90 V 90

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060   67 LAKPSIAVSPGtaieqkDMVTFYCTTK--DVNITIHWVSNNLSIVFHERMQLSKDGKI---LTILIVQREDSGTYQCEAR 141
Cdd:pfam00047   1 SAPPTVTVLEG------DSATLTCSAStgSPGPDVTWSKEGGTLIESLKVKHDNGRTTqssLLISNVTKEDAGTYTCVVN 74

                  ....*
gi 584277060  142 DALLS 146
Cdd:pfam00047  75 NPGGS 79

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 584277060   71 SIAVSPGTAieqkdmVTFYCTTK-DVNITIHWVSNNLSIVFHERMQLSKDGKI--LTILIVQREDSGTYQCEA 140
Cdd:pfam07679   9 DVEVQEGES------ARFTCTVTgTPDPEVSWFKDGQPLRSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVA 75

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 584277060 199 YTWFLLDSILSHTTR----------TFTIHAVSREHEGLYRCLVSNSATHLSS 241
Cdd:cd00096   15 ITWYKNGKPLPPSSRdsrrselgngTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060 257 QVVPSSLnlVENARSVDLTCQTVNQSVNVQWFLSGQPllPSEHLQLSADNRT---LIIHGLQRNDTGPYACEVWNWGSRA 333
Cdd:cd16843    5 SAEPSSV--VPLGENVTIRCQGPPEAVLFQLYKEGNS--LSQGTVREKEPQNkaeFYIPHMDRNHAGRYRCRYRSGTLWS 80

                         90
                 ....*....|
gi 584277060 334 R-SEPLELTI 342
Cdd:cd16843   81 EpSDPLELVV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060  256 PQVVPSSLNLVENaRSVDLTCQT-VNQSVNVQWFLSGQPLLPSehlqlsadnRTLIIHGLQRNDTGPYACEVWNWGSRAR 334
Cdd:pfam13895   2 PVLTPSPTVVTEG-EPVTLTCSApGNPPPSYTWYKDGSAISSS---------PNFFTLSVSAEDSGTYTCVARNGRGGKV 71

                  ....*...
gi 584277060  335 SEPLELTI 342
Cdd:pfam13895  72 SNPVELTV 79

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 584277060 178 EVMEGSSMTFLAETKSHPPCAYTWF-----LLDS----ILSHTTRTFTIHAVSREHEGLYRCLVSNSATHLSS 241
Cdd:cd05760   12 EIQPSSRVTLRCHIDGHPRPTYQWFrdgtpLSDGqgnySVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVCS 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 584277060 272 VDLTCQ-TVNQSVNVQWFLSGQPLL-PSEHLQLsaDNRTLIIHGLQRNDTGPYACEVWNWGSRARSEPL 338
Cdd:cd20978   19 VTLPCQvTGVPQPKITWLHNGKPLQgPMERATV--EDGTLTIINVQPEDTGYYGCVATNEIGDIYTETL 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 584277060  98 TIHWVSNNLSIVFHERMQLSKDGKiLTILIVQREDSGTYQCEARDALLSQRSDPIFLDVK 157
Cdd:cd20968   30 SVSWIKGDDLIKENNRIAVLESGS-LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTIEVE 88

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 584277060  98 TIHWVSNNLSIVFH-ERMQLSKDGKILTILIVQREDSGTYQCEARD 142
Cdd:cd04978   30 TITWRLNGVPIEPApEDMRRTVDGRTLIFSNLQPNDTAVYQCNASN 75