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 568946109 197 LVIESVPPNVVEGRDVLLLVHNMPENLRSFSWYKGVAIVSKHEISRNIITSNRSVLGPAHSGRETVYSNGSLLLHNATQK 276
Cdd:cd05774    1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                         90       100
                 ....*....|....*....|....*
gi 568946109 277 DTGLYTLLTLNRRFETQGIHVHIHI 301
Cdd:cd05774   81 DTGFYTLQTITADLQTEQASVHLQV 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 307 QPFMRV-TDTTVRVQSSVVLTCLSADTGISTQWLFNNQNLRLTERMMLSPSKCQLRIDPVRREDAGEYRCEVSNPVSSKT 385
Cdd:cd05740    1 KPFISSnNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 568946109 386 SLPVSLTV 393
Cdd:cd05740   81 SDPVTLDV 88

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 568946109 197 LVIESVPPNVVEGRDVLLLVHNMPENLRSFSWYKGVAIVSKHEISRNIITSNRSVLGPAHSGRETVYSNGSLLLHNATQK 276
Cdd:cd05774    1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                         90       100
                 ....*....|....*....|....*
gi 568946109 277 DTGLYTLLTLNRRFETQGIHVHIHI 301
Cdd:cd05774   81 DTGFYTLQTITADLQTEQASVHLQV 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 307 QPFMRV-TDTTVRVQSSVVLTCLSADTGISTQWLFNNQNLRLTERMMLSPSKCQLRIDPVRREDAGEYRCEVSNPVSSKT 385
Cdd:cd05740    1 KPFISSnNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 568946109 386 SLPVSLTV 393
Cdd:cd05740   81 SDPVTLDV 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109  314 DTTVRVQSSVVLTC-LSADTGISTQWLFNNQNLRLTERMMLS--PSKCQLRIDPVRREDAGEYRCEVSNPVSSKTSlPVS 390
Cdd:pfam07679   9 DVEVQEGESARFTCtVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA-SAE 87

                  ...
gi 568946109  391 LTV 393
Cdd:pfam07679  88 LTV 90

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 568946109   83 IDPVPQQAAKGENVLLQVHNLP---EDLRMFSWFKSMYSTQI-FKIAEYSRAFNSVIRGPAHS-RREIVYTNGSLLLQDA 157
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSsmsEASTSVYWYRQPPGKGPtFLIAYYSNGSEEGVKKGRFSgRGDPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*...
gi 568946109  158 TEKDTGMYTLQTVDRNFKIETAHVKIQI 185
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

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 568946109 197 LVIESVPPNVVEGRDVLLLVHNMPENLRSFSWYKGVAIVSKHEISRNIITSNRSVLGPAHSGRETVYSNGSLLLHNATQK 276
Cdd:cd05774    1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                         90       100
                 ....*....|....*....|....*
gi 568946109 277 DTGLYTLLTLNRRFETQGIHVHIHI 301
Cdd:cd05774   81 DTGFYTLQTITADLQTEQASVHLQV 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 307 QPFMRV-TDTTVRVQSSVVLTCLSADTGISTQWLFNNQNLRLTERMMLSPSKCQLRIDPVRREDAGEYRCEVSNPVSSKT 385
Cdd:cd05740    1 KPFISSnNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                 ....*...
gi 568946109 386 SLPVSLTV 393
Cdd:cd05740   81 SDPVTLDV 88

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 568946109  89 QAAKGENVLLQVHNLPEDLRMFSWFKSMYSTQIFKIAEYSRAFNSVIRGPAHSRREIVYTNGSLLLQDATEKDTGMYTLQ 168
Cdd:cd05741    6 YGAEGKNVLLLVPNLQTPLKSVSWYKGKQVSRNDEIAEYENSSDEFRAGSAFSGREYIYTNGSLLIQNITLSDTGFYTLE 85

                         90
                 ....*....|....*..
gi 568946109 169 TVDRNFKIETAHVKIQI 185
Cdd:cd05741   86 STNIGGKTESATFQLHV 102

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109  314 DTTVRVQSSVVLTC-LSADTGISTQWLFNNQNLRLTERMMLS--PSKCQLRIDPVRREDAGEYRCEVSNPVSSKTSlPVS 390
Cdd:pfam07679   9 DVEVQEGESARFTCtVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA-SAE 87

                  ...
gi 568946109  391 LTV 393
Cdd:pfam07679  88 LTV 90

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 568946109  199 IESVPPNVVEGRDVLLLVH---NMPENLRSFSWYKGVAIVS-KHEISRNIITSNRSVLGPAHSGRETV-YSNGSLLLHNA 273
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTyssSMSEASTSVYWYRQPPGKGpTFLIAYYSNGSEEGVKKGRFSGRGDPsNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*....
gi 568946109  274 TQKDTGLYTLLTL--NRRFETQGIHVHIH 300
Cdd:pfam07686  81 TLSDSGTYTCAVIpsGEGVFGKGTRLTVL 109

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568946109  313 TDTTVRVQSSVVLTCLS--ADTGISTQWLFNNQNLRLTERMMLSP---SKCQLRIDPVRREDAGEYRCEVSNPVSSKTS 386
Cdd:pfam00047   4 PTVTVLEGDSATLTCSAstGSPGPDVTWSKEGGTLIESLKVKHDNgrtTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82

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 568946109  90 AAKGENVLLQVHNLPEDLRMFSWFKSMystqiFKIAEYSRAFNSVIRGPAHSRREIVYTNGSLLLQDATEKDTGMYTLQT 169
Cdd:cd05775    7 GALGGNVTLTISSLQDDIDEIKWKKTK-----DKIVEWENNIGPTYFGSFKDRVLLDKESGSLTIKNLTKEDSGTYELEI 81

                 ....*...
gi 568946109 170 VDRNFKIE 177
Cdd:cd05775   82 TSTNGKVL 89

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 313 TDTTVRVQSSVVLTCLS-ADTGISTQWLFNNQNLRLTERMMLSPSKcQLRIDPVRREDAGEYRCEVSNPVSSKTSLPVSL 391
Cdd:cd20968    7 TNVTIIEGLKAVLPCTTmGNPKPSVSWIKGDDLIKENNRIAVLESG-SLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTI 85

                 ..
gi 568946109 392 TV 393
Cdd:cd20968   86 EV 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 314 DTTVRVQSSVVLTCLSADTGIST-QWLFN-NQNLRLTERMMLSPSKcQLRIDPVRREDAGEYRCEVSNPvSSKTSLPVSL 391
Cdd:cd20952    8 NQTVAVGGTVVLNCQATGEPVPTiSWLKDgVPLLGKDERITTLENG-SLQIKGAEKSDTGEYTCVALNL-SGEATWSAVL 85

                 ..
gi 568946109 392 TV 393
Cdd:cd20952   86 DV 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 306 VQPfmrvTDTTVRVQSSVVLTClSADTGIST---QWLFNNQNLRLTERMMLSPSKCQLRIDPVRREDAGEYRCEVSNPVS 382
Cdd:cd05724    2 VEP----SDTQVAVGEMAVLEC-SPPRGHPEptvSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76

                         90
                 ....*....|.
gi 568946109 383 SKTSLPVSLTV 393
Cdd:cd05724   77 ERESRAARLSV 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109 304 PVVQPFMRVTDTTVRVQSSVVLTCL---SADTGIStqWLFN-NQNLRLTERMMLSPSKCQLRIDPVRREDAGEYRCEVSN 379
Cdd:cd20970    1 PVISTPQPSFTVTAREGENATFMCRaegSPEPEIS--WTRNgNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

                         90
                 ....*....|....
gi 568946109 380 PVSSKTSLPVSLTV 393
Cdd:cd20970   79 GVPGSVEKRITLQV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568946109  196 QLVIESVPPNVVEGRDVLL--LVHNMPENlrSFSWYKGvaivskheisrniitsNRSVLGPAHSGRETVYSNGSLLLHNA 273
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLtcEATGSPPP--TITWYKN----------------GEPISSGSTRSRSLSGSNSTLTISNV 64

                  ....*....
gi 568946109  274 TQKDTGLYT 282
Cdd:pfam13927  65 TRSDAGTYT 73