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 71040102 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 71040102 223 CQVEHPAVTGnLQTQRYLEV 242
Cdd:cd05883  81 CLVDHPAVKD-LQTQRYLEV 99

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 71040102    409 LGRYFARHKGTYFTHEAKG 427
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 71040102 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 71040102 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 71040102   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 71040102 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 71040102    53 KDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQT---------IYFRDFRP--LKDSRFQLL-NFSSSELKVSLTNVSIS 120
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSMSEASTSVYWYRQPpgkgptfliAYYSNGSEegVKKGRFSGRgDPSNGDGSLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 71040102   121 DEGRYFCQLYTDPPQ--ESYTTITVL 144
Cdd:pfam07686  84 DSGTYTCAVIPSGEGvfGKGTRLTVL 109

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 71040102    409 LGRYFARHKGTYFTHEAKG 427
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 71040102 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEW-SDMYTVTSQLMLKVHKEDDGVPVI 222
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSEVEEWySRMFTVTSQLMLKVTKEDDGVPVI 80

                        90       100
                ....*....|....*....|
gi 71040102 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 71040102 144 LVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEEWS--DMYTVTSQLMLKVHKEDDGVPV 221
Cdd:cd05761   1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGagKTFTVTSTLRFRVDRDDDGVAV 80

                        90       100
                ....*....|....*....|..
gi 71040102 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 71040102  52 TKDVTVIEGEVATISCQVNKSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQLYT 131
Cdd:cd05882   4 TQDETVAVGGTVTLKCGVKEHDNSSLQWSNTAQQTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIFT 83

                        90
                ....*....|..
gi 71040102 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 71040102 143 VLVPPRNLMIDIQKDTAVEGEEIEVNCTAMASKPATTIRWFKGNKELKGKSEVEE---WSDMYTVTSQLMLKVHKEDDGV 219
Cdd:cd05884   1 VLGVPEKPQISGFTSPVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAedaNRKTFTVSSSLDFHVDRDDDGV 80

                        90       100
                ....*....|....*....|....
gi 71040102 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 71040102    255 PLQGLTREGDAFELTCEAIGKPQPvMVTWVRVDDEM---PQHAVLSGPN----LFINNLNKTDNGTYRCEASNIVGKAHS 327
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLlaeSGRFSVSRSGststLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 71040102    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 71040102   245 KPQVHIQmtyPLQGLTREGDAFELTCEAIGKPQPVmVTWVRVDDEM------PQHAVLSGPNLFINNLNKTDNGTYRCEA 318
Cdd:pfam13927   1 KPVITVS---PSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPIssgstrSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 71040102   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 71040102 262 EGDAFELTCEAIGKPQPVmVTWV----RVDDEMPQHAVLSGpNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd20978  15 GGQDVTLPCQVTGVPQPK-ITWLhngkPLQGPMERATVEDG-TLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71040102   251 QMTYPLQGLT-REGDAFELTCEAIGKPQPVmVTWVRVDDEMPQ---HAVLSGPN---LFINNLNKTDNGTYRCEASNIVG 323
Cdd:pfam07679   2 KFTQKPKDVEvQEGESARFTCTVTGTPDPE-VSWFKDGQPLRSsdrFKVTYEGGtytLTISNVQPDDSGKYTCVATNSAG 80

                  ..
gi 71040102   324 KA 325
Cdd:pfam07679  81 EA 82

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 71040102 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 71040102 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 71040102 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 71040102 147 PRNLMIdIQKDTAVEGEEIEV-NCTAMASKPATTIRWFKGNKELKGKSEVEEWSDMYTVTSQLMLKVHKEDDGVPVICQV 225
Cdd:cd05719   1 PTNSLE-GGPALLIGGEPTLVaTCISANGKPPASVTWETDLKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLTCVV 79

                        90
                ....*....|....
gi 71040102 226 EHPAVtgnLQTQRY 239
Cdd:cd05719  80 EHPSL---EKDQRI 90

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71040102 263 GDAFELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFINNLNKTdnGTYRCEASNIVGKAHS 327
Cdd:cd05749  14 NTPFNLTCQAVGPPEPVEILWWQGGSPLGGPPAPSPSVLNVPGLNET--TKFSCEAHNAKGLTSS 76

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71040102 261 REGDAFELTCEAIGkpQPVMVTWVRVDDEMPQHA--VLSGPN--LFINNLNKTDNGTYRCEASNIVGKAHSD-YMLYVY 334
Cdd:cd05740  13 EDKDAVTLTCEPET--QNTSYLWWFNGQSLPVTPrlTLSNGNrtLTLLNVTREDAGAYQCEISNPVSANRSDpVTLDVI 89

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 71040102 254 YPLQGLTREGDAFELTCEAIGKPQPVmVTWVR--------VDDEMPQHAVLSGPNLFI-----NNLNKTDNGTYRCEASN 320
Cdd:cd07693   6 HPSDLIVSKGDPATLNCKAEGRPTPT-IQWLKngqpletdKDDPRSHRIVLPSGSLFFlrvvhGRKGRSDEGVYVCVAHN 84

                ....*..
gi 71040102 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71040102 263 GDAFELTCEAIGKPQPVmVTWVRVDDEMPQHAVLS---GPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71040102 256 LQGLTREGDAFeLTCEAIGKPQPVmVTWVRVDD---EMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLY 332
Cdd:cd04969  11 KILAAKGGDVI-IECKPKASPKPT-ISWSKGTElltNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLS 88

                .
gi 71040102 333 V 333
Cdd:cd04969  89 V 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71040102    53 KDVTVIEGEVATISCQVNKSDDSVIQllnpnrqtiYFRDFRPLKDSRFQLLNFSSSELKVSLTNVSISDEGRYFCQ 128
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTIT---------WYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71040102 261 REGDAFELTCEAIGKPQPVMVTWVRVDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASN 320
Cdd:cd05754  14 RPGADVSFICRAKSKSPAYTLVWTRVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSN 73

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71040102 263 GDAFELTCEAIGKPQPVmVTWVRVDDEMPQHAVLSGPN------LFINNLNKTDNGTYRCEASNIVG 323
Cdd:cd05743   1 GETVEFTCVATGVPTPI-INWRLNWGHVPDSARVSITSeggygtLTIRDVKESDQGAYTCEAINTRG 66

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), 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 nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-1 through -4). 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. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71040102 161 EGEEIEVNCTAMASKPATTIRWfkgNKELKGKSEVE--EWSDMYTVTSQLMLKVHKEDDGVPVICQVEHPAVtgnLQTQR 238
Cdd:cd07704  16 GNETLAASCTAETGKPAASVTW---ETDLGGMESSRtfEHNRTATVTSEYHLVPTRFANGRPLTCVVSHPAL---QQDIR 89

                .
gi 71040102 239 Y 239
Cdd:cd07704  90 I 90

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71040102 253 TYPLQGLT---REGDAFELTCEAIGKPQPVmVTWVRvDDEMPQ-----HAVLS-GPNLFINNLNKTDNGTYRCEASNIV- 322
Cdd:cd20970   4 STPQPSFTvtaREGENATFMCRAEGSPEPE-ISWTR-NGNLIIefntrYIVREnGTTLTIRNIRRSDMGIYLCIASNGVp 81

                        90
                ....*....|.
gi 71040102 323 GKAHSDYMLYV 333
Cdd:cd20970  82 GSVEKRITLQV 92

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71040102 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71040102   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 71040102 262 EGDAFELTCEAIGKPQPVmVTWVR------VDDEMPQHAVLSGPNLFINNLNKTDNGTYRCEASNIVGKAHSDYMLYV 333
Cdd:cd20969  16 EGHTVQFVCRADGDPPPA-ILWLSprkhlvSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; 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. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71040102 261 REGDAFELTCEAIGKPQPVmVTWVRVDDEM--PQHA-VLSGPN---LFINNLNKTDNGTYRCEASNIVGKAHSD 328
Cdd:cd05748   5 RAGESLRLDIPIKGRPTPT-VTWSKDGQPLkeTGRVqIETTASstsLVIKNAKRSDSGKYTLTLKNSAGEKSAT 77

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 71040102 267 ELTCEAIGKPQPVmVTW----VRVDDEMPQHAVLSGpNLFINNLNKTDNGTYRCEASNIVGKAHSDYML 331
Cdd:cd05746   2 QIPCSAQGDPEPT-ITWnkdgVQVTESGKFHISPEG-YLAIRDVGVADQGRYECVARNTIGYASVSMVL 68