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 76496479 146 KPNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNR 225
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                ....*....
gi 76496479 226 SDPFNLDVI 234
Cdd:cd05740  81 SDPVTLDVI 89

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 76496479 243 SPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNITV 318
Cdd:cd20948   1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 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 76496479 146 KPNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNR 225
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                ....*....
gi 76496479 226 SDPFNLDVI 234
Cdd:cd05740  81 SDPVTLDVI 89

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 76496479 243 SPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNITV 318
Cdd:cd20948   1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

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 76496479    42 PPNVVEEKSVLLLAHNLPQE---FQVFYWYKGTTLN-PDSEIARYIRSDNMSKTGPAYSGRETI-YSNGSLFFQNVNKTD 116
Cdd:pfam07686   5 EVTVALGGSVTLPCTYSSSMseaSTSVYWYRQPPGKgPTFLIAYYSNGSEEGVKKGRFSGRGDPsNGDGSLTIQNLTLSD 84

                          90       100
                  ....*....|....*....|....*
gi 76496479   117 ERAYTLSVFDQQFNPIQTSVQFRVY 141
Cdd:pfam07686  85 SGTYTCAVIPSGEGVFGKGTRLTVL 109

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479    244 PPDIYLHQGSNLNLSCHADSNPPAQYFWL------------INEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRT 311
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYkqggkllaesgrFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*..
gi 76496479    312 TvkNITV 318
Cdd:smart00410  81 T--TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76496479   146 KPNVTGNNSNPM--EGEPfVSLMCEPYTNNT-SYLWSRNGESLSEGD--RVTFSEGNRTLTLLNVRRTDKGYYECEARN 219
Cdd:pfam13927   1 KPVITVSPSSVTvrEGET-VTLTCEATGSPPpTITWYKNGEPISSGStrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479    157 MEGEPfVSLMCEPYTNNTSYL-WSRNG-ESLSEGDR--VTFSEGNRTLTLLNVRRTDKGYYECEARNPAtFNRSDPFNLD 232
Cdd:smart00410   7 KEGES-VTLSCEASGSPPPEVtWYKQGgKLLAESGRfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSS-GSASSGTTLT 84

                   .
gi 76496479    233 V 233
Cdd:smart00410  85 V 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 76496479 146 KPNVTGNNSNPMEGEPFVSLMCEPYTNNTSYLWSRNGESLSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNPATFNR 225
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEPETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

                ....*....
gi 76496479 226 SDPFNLDVI 234
Cdd:cd05740  81 SDPVTLDVI 89

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 76496479 243 SPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVKNITV 318
Cdd:cd20948   1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479   239 APVISPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTVkNITV 318
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV-ELTV 79

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479 340 VTLTC-FSKDTGVSVRWLFNSQSLQLTD--RMTLSQDNSTLRIDPIKREDAGDYQCEISNPVSFRISHPI 406
Cdd:cd00096   1 VTLTCsASGNPPPTITWYKNGKPLPPSSrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479    244 PPDIYLHQGSNLNLSCHADSNPPAQYFWL------------INEKLQTSSQELFISNITTNNSGTYACFVNNTVTGLSRT 311
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYkqggkllaesgrFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                   ....*..
gi 76496479    312 TvkNITV 318
Cdd:smart00410  81 T--TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 76496479   240 PVI--SPPDIYLHQGSNLNLSCHADSNPPAQYFWLINEK-----------LQTSSQELFISNITTNNSGTYACFVNN 303
Cdd:pfam13927   2 PVItvSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsrsLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76496479   146 KPNVTGNNSNPM--EGEPfVSLMCEPYTNNT-SYLWSRNGESLSEGD--RVTFSEGNRTLTLLNVRRTDKGYYECEARN 219
Cdd:pfam13927   1 KPVITVSPSSVTvrEGET-VTLTCEATGSPPpTITWYKNGEPISSGStrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

IL-beta-binding protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479  157 MEGEPfVSLMCePYTNNTS-------YLWSRNGeslSEGDRVTFSEGNRTLTLLNVRRTDKGYYECEARNpATFNRSDPF 229
Cdd:PHA02785  39 LENEP-VILPC-PQINTLSsgynildILWEKRG---ADNDRIIPIDNGSNMLILNPTQSDSGIYICITKN-ETYCDMMSL 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479  230 NLDVIYGPDAPV--ISPPDIYLHQGSNL----NLSCHADSNPPAQYFW-----LINEKL-QTSSQELFISNITTNNSGTY 297
Cdd:PHA02785 113 NLTIVSVSESNIdlISYPQIVNERSTGEmvcpNINAFIASNVNADIIWsghrrLRNKRLkQRTPGIITIEDVRKNDAGYY 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479  298 ACFVNNTVTGLSR--TTVKNITVFEPVTQPSIQITNTTVKELGS-VTLTCF----SKDTGVSVRWLFNSQSLQLTD---- 366
Cdd:PHA02785 193 TCVLKYIYGDKTYnvTRIVKLEVRDRIIPPTMQLPEGVVTSIGSnLTIACRvslrPPTTDADVFWISNGMYYEEDDedgd 272

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 76496479  367 -RMTLSQD----------NSTLRIDPIKREDAGDYQC------EISNPVSFRIS 403
Cdd:PHA02785 273 gRISVANKiyttdkrrviTSRLNINPVKEEDATTFTCmaftipSISKTVTISIT 326

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 76496479 255 LNLSCHADSNPPAQYFWLINEK-----------LQTSSQELFISNITTNNSGTYACFVNNTVTGLSRTTV 313
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKplppssrdsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479    157 MEGEPfVSLMCEPYTNNTSYL-WSRNG-ESLSEGDR--VTFSEGNRTLTLLNVRRTDKGYYECEARNPAtFNRSDPFNLD 232
Cdd:smart00410   7 KEGES-VTLSCEASGSPPPEVtWYKQGgKLLAESGRfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSS-GSASSGTTLT 84

                   .
gi 76496479    233 V 233
Cdd:smart00410  85 V 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479   146 KPNVTGNNSNPMEGEPfVSLMCEPYTN-NTSYLWSRNGESLSEGDRvtfsegnrtLTLLNVRRTDKGYYECEARNPATFN 224
Cdd:pfam13895   1 KPVLTPSPTVVTEGEP-VTLTCSAPGNpPPSYTWYKDGSAISSSPN---------FFTLSVSAEDSGTYTCVARNGRGGK 70

                  ....*....
gi 76496479   225 RSDPFNLDV 233
Cdd:pfam13895  71 VSNPVELTV 79

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 76496479 244 PPDIYLHQGSNLNLSCHADSNPPAQYFWLIN-------EKLQTSSQELFISNITTNNSGTYACFVNN 303
Cdd:cd05728   6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNgqplaseNRIEVEAGDLRITKLSLSDSGMYQCVAEN 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479 321 PVTQPSIQITNTTVKELGSVTLTCFSkdTGV---SVRWLFNSQSLQLTD-RMTLSQDNSTLRIDPIKREDAGDYQCEISN 396
Cdd:cd20970   1 PVISTPQPSFTVTAREGENATFMCRA--EGSpepEISWTRNGNLIIEFNtRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

                        90
                ....*....|....
gi 76496479 397 PVSFRISHPIKLDV 410
Cdd:cd20970  79 GVPGSVEKRITLQV 92

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
                ....*....|....*....|....*....|....*....|....*
gi 76496479 177 LWSRNGESLSEGDRVTFSEGNRtLTLLNVRRTDKGYYECEARNPA 221
Cdd:cd20957  34 LWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDG 77

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
                ....*....|....*....|....*....|....*....|...
gi 76496479 178 WSRNGESLSEG-DRVTFSEGnrTLTLLNVRRTDKGYYECEARN 219
Cdd:cd20978  35 WLHNGKPLQGPmERATVEDG--TLTIINVQPEDTGYYGCVATN 75

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 76496479 330 TNTTVKELGSVTLTCFS-KDTGVSVRWLFNSQSLQLTDRMTLsQDNSTLRIDPIKREDAGDYQCEISNPVSFRISHPIKL 408
Cdd:cd20968   7 TNVTIIEGLKAVLPCTTmGNPKPSVSWIKGDDLIKENNRIAV-LESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTI 85

                ..
gi 76496479 409 DV 410
Cdd:cd20968  86 EV 87

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 76496479 178 WSRNGESLSEGD-RVTFSEGNRTLTLLNVRRTDKGYYECEARNPA 221
Cdd:cd05730  37 WTKDGEPIESGEeKYSFNEDGSEMTILDVDKLDEAEYTCIAENKA 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 76496479 178 WSRNGESLSEgDRVTFSEGNRTLTLLNVRRTDKGYYECEARN 219
Cdd:cd05876  29 WLRPSGPLPP-DRVKYQNHNKTLQLLNVGESDDGEYVCLAEN 69

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 76496479 237 PDAPVISPPDIYLHQGSNLNLSCHADSNPPAQYFW------LINEK-LQTSSQELFISNITTNNSGTYACFVNNT 304
Cdd:cd04968   1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWrkvdgsPSSQWeITTSEPVLEIPNVQFEDEGTYECEAENS 75

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 76496479 353 VRWLFNSQSLQLTDRMTLSQDNSTLRIDPIKREDAGDYQCEISNPVSFRISHPIKLDV 410
Cdd:cd05724  30 VSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAARLSV 87

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 76496479 252 GSNLNLSCHADSNpPAQYFWLINEK-LQTSSQE-------LFISNITTNNSGTYACfvnntvtgLSRTTVKNITVFEPV 322
Cdd:cd05873  11 GGNAELKCSPKSN-LARVVWKFQGKvLKAESPKyglygdgLLIFNASEADAGRYQC--------LSVEKSKAKTFFQTV 80

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 76496479 324 QPSIQitntTVKELGSVTLTCFSKDTGV-SVRWLFNSQSLQLTDRMTLSQDNsTLRIDPIKREDAGDYQCEISNPV-SFR 401
Cdd:cd20957   7 DPPVQ----TVDFGRTAVFNCSVTGNPIhTVLWMKDGKPLGHSSRVQILSED-VLVIPSVKREDKGMYQCFVRNDGdSAQ 81

                ....*..
gi 76496479 402 ISHPIKL 408
Cdd:cd20957  82 ATAELKL 88

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 76496479 178 WSRNGESLSEGDRVT-FSEGnrTLTLLNV-RRTDKGYYECEARNP 220
Cdd:cd20958  34 WEKDGRRLPLNHRQRvFPNG--TLVIENVqRSSDEGEYTCTARNQ 76

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 76496479 249 LHQGSNLNLSCHADSNPPAQYFWLINE-KLQTSSQELF---------------ISNITTNNSGTYACFVNNTV 305
Cdd:cd20956  13 LQPGPSVSLKCVASGNPLPQITWTLDGfPIPESPRFRVgdyvtsdgdvvsyvnISSVRVEDGGEYTCTATNDV 85