Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 141 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 219
Cdd:cd05883    1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                         90       100
                 ....*....|....*....|
gi 530397971 220 CQVEHPAVTGnLQTQRYLEV 239
Cdd:cd05883   81 CLVDHPAVKD-LQTQRYLEV 99

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 530397971   378 LGRYFARHKGTYFTHEAKG 396
Cdd:smart00294   1 MYRYKHRDEGSYHTHEPKG 19

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 141 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 219
Cdd:cd05883    1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                         90       100
                 ....*....|....*....|
gi 530397971 220 CQVEHPAVTGnLQTQRYLEV 239
Cdd:cd05883   81 CLVDHPAVKD-LQTQRYLEV 99

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971  242 KPQVHIQmtyPLQGLTREGDALELTCEAIGKPQPVmVTWVRVDDEM------PQHAVLSGPNLFINNLNKTDNGTYRCEA 315
Cdd:pfam13927   1 KPVITVS---PSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPIssgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 530397971  316 SN 317
Cdd:pfam13927  77 SN 78

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530397971  157 VEGEEIEVNCTAMASKPATTIRWFKGNTELKG---KSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPA 226
Cdd:pfam08205  12 GEGPEVVATCSSAGGKPAPRITWYLDGKPLEAaetSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYGA 84

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 530397971   50 KDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQT---------IYFRDFRP--LKDSRFQLL-NFSSSELKVSLTNVSIS 117
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpgkgptfliAYYSNGSEegVKKGRFSGRgDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 530397971  118 DEGRYFCQLYTDPPQ--ESYTTITVL 141
Cdd:pfam07686  84 DSGTYTCAVIPSGEGvfGKGTRLTVL 109

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 530397971   378 LGRYFARHKGTYFTHEAKG 396
Cdd:smart00294   1 MYRYKHRDEGSYHTHEPKG 19

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 141 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 219
Cdd:cd05883    1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                         90       100
                 ....*....|....*....|
gi 530397971 220 CQVEHPAVTGnLQTQRYLEV 239
Cdd:cd05883   81 CLVDHPAVKD-LQTQRYLEV 99

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one 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 and Necl-2 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 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 141 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEWS--DMYTVTSQLMLKVHKEDDGVPV 218
Cdd:cd05761    1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGagKTFTVTSTLRFRVDRDDDGVAV 80

                         90       100
                 ....*....|....*....|..
gi 530397971 219 ICQVEHPAVTG-NLQTQRYLEV 239
Cdd:cd05761   81 ICRVDHESLTStPKQTQQVLEV 102

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971  49 TKDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQLYT 128
Cdd:cd05882    4 TQDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIFT 83

                         90
                 ....*....|..
gi 530397971 129 DPPQESYTTITV 140
Cdd:cd05882   84 MPVRTAKATVTV 95

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 140 VLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEE---WSDMYTVTSQLMLKVHKEDDGV 216
Cdd:cd05884    1 VLGVPEKPQISGFTSPVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAedaNRKTFTVSSSLDFHVDRDDDGV 80

                         90       100
                 ....*....|....*....|....
gi 530397971 217 PVICQVEHPAVTGNLQ-TQRYLEV 239
Cdd:cd05884   81 AITCRVDHESLTATPQiAMQVLEI 104

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one 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 and Necl-2 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. Ig domains are likely to participate in ligand binding and recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 152 QKDTAvegeeiEVNCTAMASKPATTIRWFKGNTELKG-KSEVEEWSD--MYTVTSQLMLKVHKEDDGVPVICQVEHPAVT 228
Cdd:cd07705   18 EKDKA------KLRCTSSGSKPAANIKWRKGDQELEGaPTSVQEDGNgkTFTVSSSVEFQVTREDDGAEITCSVGHESLH 91

                 .
gi 530397971 229 G 229
Cdd:cd07705   92 D 92

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530397971 259 EGDALELTCEAIGKPQPVmVTWV----RVDDEMPQHAVLSGpNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 330
Cdd:cd20978   15 GGQDVTLPCQVTGVPQPK-ITWLhngkPLQGPMERATVEDG-TLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530397971 263 LELTCEAIGKPQPVmVTWVRVDDEMPQHAVLSGPN------LFINNLNKTDNGTYRCEASNIVGKAHS 324
Cdd:cd00096    1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSelgngtLTISNVTLEDSGTYTCVASNSAGGSAS 67

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 530397971 260 GDALELTCEAIGKPQPvMVTWVRVDDEMPQHAVL--SGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYVY 331
Cdd:cd04968   16 GQTVTLECFALGNPVP-QIKWRKVDGSPSSQWEIttSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971    50 KDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDfrplkdsRFQLlnfSSSELKVSLT--NVSISDEGRYFCQLY 127
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESG-------RFSV---SRSGSTSTLTisNVTPEDSGTYTCAAT 71

                           90
                   ....*....|....
gi 530397971   128 TDPPQ-ESYTTITV 140
Cdd:smart00410  72 NSSGSaSSGTTLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530397971  257 TREGDALELTCEAIGKPQPVmVTWVRVDDEMPQHavlsgPNLFINNLNKTDNGTYRCEASNIVGKAHSDYM 327
Cdd:pfam13895  11 VTEGEPVTLTCSAPGNPPPS-YTWYKDGSAISSS-----PNFFTLSVSAEDSGTYTCVARNGRGGKVSNPV 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530397971 259 EGDALELTCEAIGKPQPvMVTWVRVDDEMPQH---AVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHS 324
Cdd:cd20968   13 EGLKAVLPCTTMGNPKP-SVSWIKGDDLIKENnriAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

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 530397971  254 QGLTREGDALELTCEAIGKPQPVMVTWVRVDDEMPQ-HAVLSGPN------LFINNLNKTDNGTYRCEASNIVGKA 322
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIEsLKVKHDNGrttqssLLISNVTKEDAGTYTCVVNNPGGSA 80

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; 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 and 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, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530397971 260 GDALELTCEAIGKPQPVmVTWVRVDDEMPQHAVLS---GPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 330
Cdd:cd05731   10 GGVLLLECIAEGLPTPD-IRWIKLGGELPKGRTKFenfNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 253 LQGLTREGDALeLTCEAIGKPQPVmVTWVRVDD---EMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLY 329
Cdd:cd04969   11 KILAAKGGDVI-IECKPKASPKPT-ISWSKGTElltNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLS 88

                 .
gi 530397971 330 V 330
Cdd:cd04969   89 V 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530397971 258 REGDALELTCEAIGkpQPVMVTWVRVDDEMPQHA--VLSGPN--LFINNLNKTDNGTYRCEASNIVGKAHSD-YMLYVY 331
Cdd:cd05740   13 EDKDAVTLTCEPET--QNTSYLWWFNGQSLPVTPrlTLSNGNrtLTLLNVTREDAGAYQCEISNPVSANRSDpVTLDVI 89

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 530397971   50 KDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQT---------IYFRDFRP--LKDSRFQLL-NFSSSELKVSLTNVSIS 117
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpgkgptfliAYYSNGSEegVKKGRFSGRgDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 530397971  118 DEGRYFCQLYTDPPQ--ESYTTITVL 141
Cdd:pfam07686  84 DSGTYTCAVIPSGEGvfGKGTRLTVL 109

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 530397971 259 EGDALELTCEAIGKPQPvMVTWVRVDDEMPQHAVLSGPN---LFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 330
Cdd:cd05876    9 RGQSLVLECIAEGLPTP-TVKWLRPSGPLPPDRVKYQNHnktLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 251 YPLQGLTREGDALELTCEAIGKPQPVmVTWVR--------VDDEMPQHAVLSGPNLFI-----NNLNKTDNGTYRCEASN 317
Cdd:cd07693    6 HPSDLIVSKGDPATLNCKAEGRPTPT-IQWLKngqpletdKDDPRSHRIVLPSGSLFFlrvvhGRKGRSDEGVYVCVAHN 84

                 ....*..
gi 530397971 318 IVGKAHS 324
Cdd:cd07693   85 SLGEAVS 91

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 258 REGDALELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASN 317
Cdd:cd05754   14 RPGADVSFICRAKSKSPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSN 73

Seventh 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 seventh 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530397971 260 GDALELTCEAIGKPQPvMVTWVRVDDEMP--QHAVLSGPN--------LFINNLNKTDNGTYRCEASNIVG 320
Cdd:cd20954   16 GQDVMLHCQADGFPTP-TVTWKKATGSTPgeYKDLLYDPNvrilpngtLVFGHVQKENEGHYLCEAKNGIG 85

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530397971 260 GDALELTCEAIGKPQPVmVTW------------VRVDDEMPQHA-VLSGPNlfINNLNKTDNGTYRCEASNIVGKA-HS 324
Cdd:cd20956   16 GPSVSLKCVASGNPLPQ-ITWtldgfpipesprFRVGDYVTSDGdVVSYVN--ISSVRVEDGGEYTCTATNDVGSVsHS 91

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 243 PQVHIQMTyPLQGLTREGDALELTCE-AIGKPQPVMVTWVRVDDEMPQHAVLSgpnLFINNLNKTDNGTYRCEASNIVGK 321
Cdd:cd20937    1 PKLEIKVT-PSDAIVREGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFT---LNLREVTKDQSGKYCCQVSNDVGP 76

                 ...
gi 530397971 322 AHS 324
Cdd:cd20937   77 GRS 79

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530397971 260 GDALELTCEAIGKPQPVmVTWVRVDDEMPQHAVLSGPN------LFINNLNKTDNGTYRCEASNIVG 320
Cdd:cd05743    1 GETVEFTCVATGVPTPI-INWRLNWGHVPDSARVSITSeggygtLTIRDVKESDQGAYTCEAINTRG 66

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 530397971 259 EGDALELTCEAIGKPQPVmVTWVR------VDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 330
Cdd:cd20969   16 EGHTVQFVCRADGDPPPA-ILWLSprkhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530397971 252 PLQGLTREGDALELTCEAIGKPQPVmVTWVRVDDE-MPQH--AVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYML 328
Cdd:cd05723    4 PSNIYAHESMDIVFECEVTGKPTPT-VKWVKNGDVvIPSDyfKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

                 ..
gi 530397971 329 YV 330
Cdd:cd05723   83 II 84

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530397971  158 EGEEIEVNCTAMASKPATTIRWFKGNTELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVpVICQVEHP 225
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGT-YTCVVNNP 76