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 46575940 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 46575940 223 CQVEHPAVTGnLQTQRYLEV 242
Cdd:cd05883  81 CLVDHPAVKD-LQTQRYLEV 99

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 46575940    381 LGRYFARHKGTYFTHEAKG 399
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 46575940 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 46575940 223 CQVEHPAVTGnLQTQRYLEV 242
Cdd:cd05883  81 CLVDHPAVKD-LQTQRYLEV 99

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46575940   160 VEGEEIEVNCTAMASKPATTIRWFKGNKELKG---KSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPA 229
Cdd:pfam08205  12 GEGPEVVATCSSAGGKPAPRITWYLDGKPLEAaetSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYGA 84

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 46575940 266 FELTCEAIGKPQPVmVTWVRVDDEMPQHAVLSGPN------LFINNLNKTDNGTYRCEASNIVGKAHS 327
Cdd:cd00096   1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRSelgngtLTISNVTLEDSGTYTCVASNSAGGSAS 67

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 46575940    53 KDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQT---------IYFRDFRP--LKDSRFQLL-NFSSSELKVSLTNVSIS 120
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpgkgptfliAYYSNGSEegVKKGRFSGRgDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 46575940   121 DEGRYFCQLYTDPPQ--ESYTTITVL 144
Cdd:pfam07686  84 DSGTYTCAVIPSGEGvfGKGTRLTVL 109

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 46575940    381 LGRYFARHKGTYFTHEAKG 399
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 46575940 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 46575940 223 CQVEHPAVTGnLQTQRYLEV 242
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 46575940 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEWS--DMYTVTSQLMLKVHKEDDGVPV 221
Cdd:cd05761   1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGagKTFTVTSTLRFRVDRDDDGVAV 80

                        90       100
                ....*....|....*....|..
gi 46575940 222 ICQVEHPAVTG-NLQTQRYLEV 242
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 46575940  52 TKDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQLYT 131
Cdd:cd05882   4 TQDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIFT 83

                        90
                ....*....|..
gi 46575940 132 DPPQESYTTITV 143
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 46575940 143 VLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEE---WSDMYTVTSQLMLKVHKEDDGV 219
Cdd:cd05884   1 VLGVPEKPQISGFTSPVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAedaNRKTFTVSSSLDFHVDRDDDGV 80

                        90       100
                ....*....|....*....|....
gi 46575940 220 PVICQVEHPAVTGNLQ-TQRYLEV 242
Cdd:cd05884  81 AITCRVDHESLTATPQiAMQVLEI 104

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940    255 PLQGLTREGDAFELTCEAIGKPQPvMVTWVRVDDEM---PQHAVLSGPN----LFINNLNKTDNGTYRCEASNIVGKAHS 327
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLlaeSGRFSVSRSGststLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 46575940    328 DYMLYV 333
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940   245 KPQVHIQmtyPLQGLTREGDAFELTCEAIGKPQPVmVTWVRVDDEM------PQHAVLSGPNLFINNLNKTDNGTYRCEA 318
Cdd:pfam13927   1 KPVITVS---PSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPIssgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 46575940   319 SN 320
Cdd:pfam13927  77 SN 78

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 46575940 262 EGDAFELTCEAIGKPQPVmVTWV----RVDDEMPQHAVLSGpNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd20978  15 GGQDVTLPCQVTGVPQPK-ITWLhngkPLQGPMERATVEDG-TLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 248 VHIQMTYPLQGltregDAFELTCEAIGKPQPVmVTWVRVDDEMPQHA--VLSGPNLFINNLNKTDNGTYRCEASNIVGKA 325
Cdd:cd05851   6 VKFKDTYALKG-----QNVTLECFALGNPVPV-IRWRKILEPMPATAeiSMSGAVLKIFNIQPEDEGTYECEAENIKGKD 79

                ....*...
gi 46575940 326 HSDYMLYV 333
Cdd:cd05851  80 KHQARVYV 87

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 46575940 263 GDAFELTCEAIGKPQPvMVTWVRVDDEMPQHAVL--SGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYVY 334
Cdd:cd04968  16 GQTVTLECFALGNPVP-QIKWRKVDGSPSSQWEIttSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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 46575940 263 GDAFELTCEAIGKPQPVmVTWVRVDDEMP--QHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd05725  12 DDSAEFQCEVGGDPVPT-VRWRKEDGELPkgRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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 46575940 262 EGDAFELTCEAIGKPQPvMVTWVRVDDEMPQH---AVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHS 327
Cdd:cd20968  13 EGLKAVLPCTTMGNPKP-SVSWIKGDDLIKENnriAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 147 PRNLMIdIQKDTAVEGEEIEV-NCTAMASKPATTIRWFKGNKELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQV 225
Cdd:cd05719   1 PTNSLE-GGPALLIGGEPTLVaTCISANGKPPASVTWETDLKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLTCVV 79

                        90
                ....*....|....
gi 46575940 226 EHPAVtgnLQTQRY 239
Cdd:cd05719  80 EHPSL---EKDQRI 90

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46575940   257 QGLTREGDAFELTCEAIGKPQPVMVTWVRVDDEMPQ-HAVLSGPN------LFINNLNKTDNGTYRCEASNIVGKA 325
Cdd:pfam00047   5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIEsLKVKHDNGrttqssLLISNVTKEDAGTYTCVVNNPGGSA 80

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46575940 262 EGDAFELTCEAIGKPQPVmVTWV---RVDDEMPQHAVLS--GPNLFINNLNKTDNGTYRCEASNIVG 323
Cdd:cd04978  13 PGETGELICEAEGNPQPT-ITWRlngVPIEPAPEDMRRTvdGRTLIFSNLQPNDTAVYQCNASNVHG 78

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 254 YPLQGLTREGDAFELTCEAIGKPQPVmVTWVR--------VDDEMPQHAVLSGPNLFI-----NNLNKTDNGTYRCEASN 320
Cdd:cd07693   6 HPSDLIVSKGDPATLNCKAEGRPTPT-IQWLKngqpletdKDDPRSHRIVLPSGSLFFlrvvhGRKGRSDEGVYVCVAHN 84

                ....*..
gi 46575940 321 IVGKAHS 327
Cdd:cd07693  85 SLGEAVS 91

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 46575940 263 GDAFELTCEAIGKPQPVmVTWVRVDDEMPQHAVLS---GPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd05731  10 GGVLLLECIAEGLPTPD-IRWIKLGGELPKGRTKFenfNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 169 CTAMASKPATTIRWFKG-NKELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQVEH 227
Cdd:cd07703  22 CVSANGRPPARISWSSTlNGNANTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTCKVEH 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46575940    53 KDVTVIEGEVATISCQVNKSDDSVIQllnpnrqtiYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQ 128
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTIT---------WYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46575940 268 LTCEAIGKPQPvMVTWVRVDDEMP--QHAVLSGPN--------LFINNLNKTDNGTYRCEASNIVG 323
Cdd:cd20954  21 LHCQADGFPTP-TVTWKKATGSTPgeYKDLLYDPNvrilpngtLVFGHVQKENEGHYLCEAKNGIG 85

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 254 YPLQGLTREGDAFELTCEAIGKPQPvMVTWVR----VDDEMPQHAVL--SGPNLFINNLNKTDNGTYRCEASNIVGKAHS 327
Cdd:cd05736   6 YPEFQAKEPGVEASLRCHAEGIPLP-RVQWLKngmdINPKLSKQLTLiaNGSELHISNVRYEDTGAYTCIAKNEGGVDED 84

                ....*....
gi 46575940 328 DYMLYVYDT 336
Cdd:cd05736  85 ISSLFVEDS 93

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 46575940 253 TYPLQGLT---REGDAFELTCEAIGKPQPVmVTWVRvDDEMPQ-----HAVLS-GPNLFINNLNKTDNGTYRCEASNIV- 322
Cdd:cd20970   4 STPQPSFTvtaREGENATFMCRAEGSPEPE-ISWTR-NGNLIIefntrYIVREnGTTLTIRNIRRSDMGIYLCIASNGVp 81

                        90
                ....*....|.
gi 46575940 323 GKAHSDYMLYV 333
Cdd:cd20970  82 GSVEKRITLQV 92

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 246 PQVHIQMTyPLQGLTREGDAFELTCE-AIGKPQPVMVTWVRVDDEMPQHAVLSgpnLFINNLNKTDNGTYRCEASNIVGK 324
Cdd:cd20937   1 PKLEIKVT-PSDAIVREGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFT---LNLREVTKDQSGKYCCQVSNDVGP 76

                ...
gi 46575940 325 AHS 327
Cdd:cd20937  77 GRS 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 46575940 261 REGDAFELTCEAIGKPQPVmVTWVRVDDEMPQHAV------LSGPNLFINNLNKTDNGTYRCEASNIVGKA 325
Cdd:cd20949  12 KEGQSATILCEVKGEPQPN-VTWHFNGQPISASVAdmskyrILADGLLINKVTQDDTGEYTCRAYQVNSIA 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46575940   161 EGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVpVICQVEHP 228
Cdd:pfam00047  10 EGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGT-YTCVVNNP 76

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 46575940 262 EGDAFELTCEAIGKPQPVmVTWVR------VDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd20969  16 EGHTVQFVCRADGDPPPA-ILWLSprkhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46575940 267 ELTCEAIGKPQPVmVTW----VRVDDEMPQHAVLSGpNLFINNLNKTDNGTYRCEASNIVGKAHSDYML 331
Cdd:cd05746   2 QIPCSAQGDPEPT-ITWnkdgVQVTESGKFHISPEG-YLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46575940 267 ELTCEAIGKPQPVmVTWVRVDDE-MPQH--AVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd05723  16 VFECEVTGKPTPT-VKWVKNGDVvIPSDyfKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84