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 257096063  41 NYTVCEGDNATLSCFIDE-HVTRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITQVGLGDEGLYTCSFQTRh 118
Cdd:cd05717    5 DVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYTD- 83

                         90
                 ....*....|.
gi 257096063 119 QPYTTQVYLIV 129
Cdd:cd05717   84 PVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257096063  134 RIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTW----------RQLRDGFTSEGEILEISDIQRGQAGEYECVTHN 199
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWykngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063  41 NYTVCEGDNATLSCFIDE-HVTRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITQVGLGDEGLYTCSFQTRh 118
Cdd:cd05717    5 DVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYTD- 83

                         90
                 ....*....|.
gi 257096063 119 QPYTTQVYLIV 129
Cdd:cd05717   84 PVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257096063  134 RIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTW----------RQLRDGFTSEGEILEISDIQRGQAGEYECVTHN 199
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWykngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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 257096063   139 SSPVAVNEGGNVNLLCLAVGRPEPTVTWRQ-------LRDGFTSEGE----ILEISDIQRGQAGEYECVTHNGVNSApdS 207
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqggkllaESGRFSVSRSgstsTLTISNVTPEDSGTYTCAATNSSGSA--S 78

                   ....*..
gi 257096063   208 RRVLVTV 214
Cdd:smart00410  79 SGTTLTV 85

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 257096063   230 LGRAALLRCEAMAVPPADFQWYKDDRLLSSGSaEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 306
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGGKLLAES-GRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063   37 SPADNYTVCEGDNATLSCFI--DEHVTRVAWLNRSNILYAGNDRWTSDPRVRllintpeEFSILITQVGLGDEGLYTCSF 114
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAstGSPGPDVTWSKEGGTLIESLKVKHDNGRTT-------QSSLLISNVTKEDAGTYTCVV 73

                  ....*....
gi 257096063  115 QTRHQPYTT 123
Cdd:pfam00047  74 NNPGGSATL 82

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063  41 NYTVCEGDNATLSCFIDE-HVTRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITQVGLGDEGLYTCSFQTRh 118
Cdd:cd05717    5 DVTVVEGETLTLKCQVSLrDDSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHYTD- 83

                         90
                 ....*....|.
gi 257096063 119 QPYTTQVYLIV 129
Cdd:cd05717   84 PVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257096063  134 RIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTW----------RQLRDGFTSEGEILEISDIQRGQAGEYECVTHN 199
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWykngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257096063  43 TVCEGDNATLSCFIDEHV-TRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITQVGLGDEGLYTCSFQT 116
Cdd:cd05882    8 TVAVGGTVTLKCGVKEHDnSSLQWSNTAQqTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIFT 83

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 257096063  231 GRAALLRCEAMAVPPADFQWYKDDRLLSSGSAegLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 306
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKDGQPLRSSDR--FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88

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 257096063 234 ALLRCEAMAVPPADFQWYKDDRLLSSGSAEglKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSAS 303
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRD--SRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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 257096063 132 PARIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTWRQLrDG-------FTSEGEILEISDIQRGQAGEYECVTHN 199
Cdd:cd04968    1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKV-DGspssqweITTSEPVLEIPNVQFEDEGTYECEAEN 74

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 257096063 139 SSPVAVNEGGNVNLLCLAVGRPEPTVTWRqlRDG-----------FTSEGEILEISDIQRGQAGEYECVTHNGVNSAPDS 207
Cdd:cd20970    9 SFTVTAREGENATFMCRAEGSPEPEISWT--RNGnliiefntryiVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSVEK 86

                 ....*
gi 257096063 208 RRVLV 212
Cdd:cd20970   87 RITLQ 91

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063 218 PTITDVTSARTALGRAALLRCEAMAVPPA-DFQWYKDDRLLSS-GSAEGLKVQTERTRSMLLFANVSARHYGNYTCRAAN 295
Cdd:cd05895    1 PKLKEMKSQEVAAGSKLVLRCETSSEYPSlRFKWFKNGKEINRkNKPENIKIQKKKKKSELRINKASLADSGEYMCKVSS 80

                 ....*...
gi 257096063 296 RLGASSAS 303
Cdd:cd05895   81 KLGNDSAS 88

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 257096063  230 LGRAALLRCEA-MAVPPADFQWYKDD-RLLSSgsAEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 306
Cdd:pfam00047  10 EGDSATLTCSAsTGSPGPDVTWSKEGgTLIES--LKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063  219 TITDVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSSGSAeglkvqtertrsmLLFANVSARHYGNYTCRAAN-RL 297
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPN-------------FFTLSVSAEDSGTYTCVARNgRG 68

                  ....*....
gi 257096063  298 GASSASMRL 306
Cdd:pfam13895  69 GKVSNPVEL 77

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063    41 NYTVCEGDNATLSC-FIDEHVTRVAWLNRSNILYAGNDRWTsdprvrlLINTPEEFSILITQVGLGDEGLYTCSFQTRHQ 119
Cdd:smart00410   3 SVTVKEGESVTLSCeASGSPPPEVTWYKQGGKLLAESGRFS-------VSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

                           90
                   ....*....|
gi 257096063   120 PYTTQVYLIV 129
Cdd:smart00410  76 SASSGTTLTV 85

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule 2; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-2, Necl-2 (also known as cell adhesion molecule 1 (CADM1), SynCAM1, IGSF4A, Tslc1, sgIGSF, and RA175). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063  40 DNYTVCEGDNATLSCFI---DEHVTRVAWLNRSNIlYAGNDRWTSDPRVRLLINTPEEFSILITQVGLGDEGLYTCSFQT 116
Cdd:cd05881    4 EDVTVVEGEVATISCRVknsDDSVIQLLNPNRQTI-YFRDFRPLKDSRFQLVNFSSSELRVSLTNVSISDEGRYFCQLYT 82

                 ....*....
gi 257096063 117 R--HQPYTT 123
Cdd:cd05881   83 DppQEAYTT 91

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063  134 RIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTWRqlRDG-FTSEGEILEISDIQRGQAGEYECVTHNGVNSaPDSRRVLV 212
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWY--KDGsAISSSPNFFTLSVSAEDSGTYTCVARNGRGG-KVSNPVEL 77

                  ..
gi 257096063  213 TV 214
Cdd:pfam13895  78 TV 79

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 257096063 144 VNEGGNVNLLCLAVGRPEPTVTWRQLRDGFTSEGE------ILEISDIQrgQAGEYECV 196
Cdd:cd05739    9 VMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEmpvgrnVLELTNIY--ESANYTCV 65

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 257096063 228 TALGRAALLRCEAMAVPPADFQWYKDDRLLSSGSAEGLKVQTERTRsmllfaNVSARHYGNYTCRAANRLGASSASMRL 306
Cdd:cd05725    9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDHSLKIR------KVTAGDMGSYTCVAENMVGKIEASATL 81

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 257096063 142 VAVNEGGNVNLLCLAVGRPEPTVTWRQLRDGFTSEGEI-------LEISDIQRGQAGEYECVTHNGVNSAPdSRRVLVTV 214
Cdd:cd20968    9 VTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIavlesgsLRIHNVQKEDAGQYRCVAKNSLGIAY-SKPVTIEV 87

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063 218 PTITDVTSartalGRAALLRCEAMAVPPADFQWYKDDRLLSSGSAEGLKVQTerTRSMLLFANVSARHYGNYTCRAANRL 297
Cdd:cd20949    6 AYVTTVKE-----GQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRI--LADGLLINKVTQDDTGEYTCRAYQVN 78

                 ....
gi 257096063 298 GASS 301
Cdd:cd20949   79 SIAS 82

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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063 140 SPVAVNEGGNVNLLCLAVGRPEPTVTWR---------QLRDGFTSEGEILEISDIQRGQAGEYECVTHNG 200
Cdd:cd04978    7 PSLVLSPGETGELICEAEGNPQPTITWRlngvpiepaPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 257096063 231 GRAALLRCEAMAVPPADFQWYKDDRLLSSGSAEGLKVQTERTRSmLLFANVSARHYGNYTCRAANRLGASSASMRLL 307
Cdd:cd20990   15 GKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHS-LIIEPVTSRDAGIYTCIATNRAGQNSFNLELV 90

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 257096063 139 SSPVAVNEGGNVNLLCLAVGRPEPTVTWRqLRDGFTSEGEILEISDIQRGQAGEYECVTHNGVNSAPDSRRVLVTV 214
Cdd:cd20948    2 PSDTYYLSGENLNLSCHAASNPPAQYSWT-INGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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 257096063 131 VPARIVNISSPVAVNEGGNVNLLCLAVGRPEPTVTWrqLRDG------------FTSEGEILEISDIQRGQAGEYECVTH 198
Cdd:cd05747    2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTW--MREGqiivssqrhqitSTEYKSTFEISKVQMSDEGNYTVVVE 79

                 .
gi 257096063 199 N 199
Cdd:cd05747   80 N 80

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063 218 PTITDVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSS--GSAEGLKVQTERTR-SMLLFANVSARHYGNYTCRAA 294
Cdd:cd05732    3 PKITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFeeGDLDGRIVVRGHARvSSLTLKDVQLTDAGRYDCEAS 82

                         90
                 ....*....|..
gi 257096063 295 NRLGASSASMRL 306
Cdd:cd05732   83 NRIGGDQQSMYL 94

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 257096063 138 ISSP---VAVNEGGNVNLLCLAVGRPEPTVTWRQLRDGFTSEGEI-------LEISDIQRGQAGEYECVthnGVNSAPD- 206
Cdd:cd20978    4 IQKPeknVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERatvedgtLTIINVQPEDTGYYGCV---ATNEIGDi 80

                 ....*...
gi 257096063 207 SRRVLVTV 214
Cdd:cd20978   81 YTETLLHV 88

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 257096063 229 ALGRAALLRCEAMAVPPADFQWYKDDRLLSSGSAegLKVQTERTrsmLLFANVSARHYGNYTCRAANRLGASSAS 303
Cdd:cd04969   15 AKGGDVIIECKPKASPKPTISWSKGTELLTNSSR--ICILPDGS---LKIKNVTKSDEGKYTCFAVNFFGKANST 84

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 257096063 147 GGNVNLLCLAVGRPEPTVTWRQlrdgftSEGEI------------LEISDIQRGQAGEYECVTHNGVNSAPDSRRVLV 212
Cdd:cd05725   12 DDSAEFQCEVGGDPVPTVRWRK------EDGELpkgryeilddhsLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 257096063 231 GRAALLRCEAMAVPPADFQWYKDDRLLSSgSAEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRLL 307
Cdd:cd20973   12 GSAARFDCKVEGYPDPEVKWMKDDNPIVE-SRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 257096063 236 LRCEAMAVPPADFQWYKDDrllsSGSAEGLKVQterTRSMLLFANVSARHYGNYTCRAANRLGASSAS 303
Cdd:cd16082   18 LQCQAWGSPPISYVWYKEQ----TNNQEPIKVA---ALSTLLFKPAVVADSGSYFCTAKGRVGSEQRS 78