First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; 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-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  35 VPLVQNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCS 114
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1207108497 115 LFTMPVKTAKAFLTVL 130
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207108497 233 PYVEIRQSTNVPQEGQYLKLQCVPKGNPSPDpVLWTKDGGELPD----MDRMIVDGRDLTFTSLNKTDNGTYRCEATN 306
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSgstrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; 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-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  35 VPLVQNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCS 114
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1207108497 115 LFTMPVKTAKAFLTVL 130
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 136 PEINGLtKPVLEGDHI--TLTCVTSGSKPAADVRWFKNEMEVKGAK---EVNASGKTFTVKSSLRLHVNRDDDGVAYTCR 210
Cdd:pfam08205   1 PTIEPP-ASLLEGEGPevVATCSSAGGKPAPRITWYLDGKPLEAAEtssEQDPESGLVTVTSELKLVPSRSDHGQSLTCQ 79

                          90
                  ....*....|
gi 1207108497 211 VDHVALTATH 220
Cdd:pfam08205  80 VSYGALRGSI 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207108497 233 PYVEIRQSTNVPQEGQYLKLQCVPKGNPSPDpVLWTKDGGELPD----MDRMIVDGRDLTFTSLNKTDNGTYRCEATN 306
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSgstrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  245 QEGQYLKLQCVPKGNPSPDpVLWTKDGGELPDM-DRMIVDGRD----LTFTSLNKTDNGTYRCEATNHLGTSHAEFKLVI 319
Cdd:smart00410   7 KEGESVTLSCEASGSPPPE-VTWYKQGGKLLAEsGRFSVSRSGststLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207108497  145 VLEGDHITLTCVTSGSkPAADVRWFKNEMEVKGAKEvNASGKTFTVKSSLRLH-VNRDDDGVaYTCRV 211
Cdd:smart00410   6 VKEGESVTLSCEASGS-PPPEVTWYKQGGKLLAESG-RFSVSRSGSTSTLTISnVTPEDSGT-YTCAA 70

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; 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-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  35 VPLVQNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCS 114
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1207108497 115 LFTMPVKTAKAFLTVL 130
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

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 1207108497 130 LGVPKKPEINGLTKPVLEGDHITLTCVTSGSKPAADVRWFKNEMEVKGAKEVNASG--KTFTVKSSLRLHVNRDDDGVAY 207
Cdd:cd05761     1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGagKTFTVTSTLRFRVDRDDDGVAV 80

                          90       100
                  ....*....|....*....|..
gi 1207108497 208 TCRVDHVALTATHEETTQVLEV 229
Cdd:cd05761    81 ICRVDHESLTSTPKQTQQVLEV 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  36 PLVQNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCSL 115
Cdd:cd05717     1 PHTQDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLH 80

                          90
                  ....*....|....
gi 1207108497 116 FTMPVKTAKAFLTV 129
Cdd:cd05717    81 YTDPVSTKKVTVTV 94

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  37 LVQNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCSLF 116
Cdd:cd05881     2 VTEDVTVVEGEVATISCRVKNSDDSVIQLLNPNRQTIYFRDFRPLKDSRFQLVNFSSSELRVSLTNVSISDEGRYFCQLY 81

                          90
                  ....*....|...
gi 1207108497 117 TMPVKTAKAFLTV 129
Cdd:cd05881    82 TDPPQEAYTTITV 94

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); 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-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. 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 1207108497 133 PKKPEINGLTKPVlEGDHITLTCVTSGSKPAADVRWFKNEMEVKGAKEVNASGKTFTVKSSLRLHVNRDDDGVAYTCRVD 212
Cdd:cd05885     4 PENPVVEVREQAV-EGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQENGKVWSVASTVRFRVDRKDDGGIVICEAQ 82

                          90
                  ....*....|....*...
gi 1207108497 213 HVALTATHEETTQ-VLEV 229
Cdd:cd05885    83 NQALPSGHSKQTQyVLDV 100

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497   39 QNMTVTEGGTANLTCRVEHNDNTSLQWSNPAQQTLFFGDkkalrdnRIELVRaTSQELTISISEVSLSDEGLYTCSL-FT 117
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESG-------RFSVSR-SGSTSTLTISNVTPEDSGTYTCAAtNS 73

                           90
                   ....*....|..
gi 1207108497  118 MPVKTAKAFLTV 129
Cdd:smart00410  74 SGSASSGTTLTV 85

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 239 QSTNVPQEGQYLKLQCVPKGNPSPDpVLWTKDGGELPDmDRMIVD--GRDLTFTSLNKTDNGTYRCEATNHLGTSHAEFK 316
Cdd:cd05731     2 ESSTMVLRGGVLLLECIAEGLPTPD-IRWIKLGGELPK-GRTKFEnfNKTLKIENVSEADSGEYQCTASNTMGSARHTIS 79

                  ...
gi 1207108497 317 LVI 319
Cdd:cd05731    80 VTV 82

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, 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 of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 136 PEINGltKPV---LEGDHITLTCVTSGSKPAADVRWFKNEMEVKGA---KEVNASGKTFTVKSSLRLHVNRDDDGVAYTC 209
Cdd:cd05759     2 PVIEG--GPVislQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAvysKELLKDGKRETTVSTLLITPSDLDTGRTFTC 79

                          90       100
                  ....*....|....*....|
gi 1207108497 210 RVDHVALtATHEETTQVLEV 229
Cdd:cd05759    80 RARNEAI-PNGKETSITLDV 98

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 1207108497 247 GQYLKLQCVPKGNPSPDpVLWTKDGGELPDMDRMIVDGRDLTFTSLNKTDNGTYRCEATNHLGTSHAEFKLVI 319
Cdd:cd05725    12 DDSAEFQCEVGGDPVPT-VRWRKEDGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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 1207108497 250 LKLQCVPKGNPSPDpVLWTKDGGELP----DMDRMIVDGRDLTFTSLNKTDNGTYRCEATNHLGTS 311
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPpssrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGS 65

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 233 PYVEIRQS-TNVPQE-GQYLKLQCVPKGNPSPDpVLWTKDGGELPDMDRMIV---DGRDLTFTSLNKTDNGTYRCEATNH 307
Cdd:cd05730     2 PTIRARQSeVNATANlGQSVTLACDADGFPEPT-MTWTKDGEPIESGEEKYSfneDGSEMTILDVDKLDEAEYTCIAENK 80

                          90
                  ....*....|...
gi 1207108497 308 LGTSHAEFKLVIY 320
Cdd:cd05730    81 AGEQEAEIHLKVF 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 233 PYVEIRQSTNVPQ-EGQYLKLQCVPKGNPSPDpVLWTKDGGEL-PDMDRMIVDGRDLTFTSLNKTDNGTYRCEATNHLGT 310
Cdd:cd20978     1 PKFIQKPEKNVVVkGGQDVTLPCQVTGVPQPK-ITWLHNGKPLqGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGD 79

                  ....*....
gi 1207108497 311 SHAEFKLVI 319
Cdd:cd20978    80 IYTETLLHV 88

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 144 PVLEGDHITLTCVTSGSKPA-ADVRWFKN----EMEVKGAKEVNASGKTFTVKSSLRLHVNRDDDGVAYTCRVDHVALTA 218
Cdd:cd00098    10 EEKGGGKVTLVCLVSGFYPKdITVTWLKNgvplTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDEGATYTCVVTHESLKS 89

                  .
gi 1207108497 219 T 219
Cdd:cd00098    90 P 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 139 NGLTKPVLEGDHITLTCVTSGSkPAADVRWFKNEMEVKGAKE---VNASGKTFTVKSslrlhVNRDDDGvAYTCRVDH-V 214
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGS-PEPEISWTRNGNLIIEFNTryiVRENGTTLTIRN-----IRRSDMG-IYLCIASNgV 80

                          90
                  ....*....|..
gi 1207108497 215 ALTATHEETTQV 226
Cdd:cd20970    81 PGSVEKRITLQV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497  39 QNMTVTEGGTANLTCRVEHNDNTSLQWsnpaqqtlfFGDKKALRDNRIELVRATSQELTISISEVSLSDEGLYTCSLfTM 118
Cdd:pfam07679   8 KDVEVQEGESARFTCTVTGTPDPEVSW---------FKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVA-TN 77

                          90
                  ....*....|...
gi 1207108497 119 PVK--TAKAFLTV 129
Cdd:pfam07679  78 SAGeaEASAELTV 90

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 1207108497 135 KPEINGlTKPVLEGDHITL--TCVTSGSKPAADVRWfknEMEVKG---AKEVNASGKTFTVKSSLRLHVNRDDDGVAYTC 209
Cdd:cd05719     2 TNSLEG-GPALLIGGEPTLvaTCISANGKPPASVTW---ETDLKGeasTTQVRGSNGTVTVTSRYRLVPSREADGQPLTC 77

                  ....*..
gi 1207108497 210 RVDHVAL 216
Cdd:cd05719    78 VVEHPSL 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 135 KPEINGLTKP--VLEGDHITLTCVTSGSkPAADVRWFKNEMEVKGakEVNASGKTFTVKSSLRLH-VNRDDDGVaYTCRV 211
Cdd:pfam13927   1 KPVITVSPSSvtVREGETVTLTCEATGS-PPPTITWYKNGEPISS--GSTRSRSLSGSNSTLTISnVTRSDAGT-YTCVA 76

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 245 QEGQYLKLQCVPKGNPSPDpVLWTKDGGELPDMDR--MIVD--GR-DLTFTSLNKTDNGTYRCEATNHLGTSHAEFKLVI 319
Cdd:cd05744    13 QEGRLCRFDCKVSGLPTPD-LFWQLNGKPVRPDSAhkMLVRenGRhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207108497 239 QSTNVPQEGQYLKLQCVPKGNPSPDpVLWTKDGGELPDmDRMIVDGRDLTFTSLN--KTDNGTYRCEATNHLGTS 311
Cdd:cd05876     2 SSSLVALRGQSLVLECIAEGLPTPT-VKWLRPSGPLPP-DRVKYQNHNKTLQLLNvgESDDGEYVCLAENSLGSA 74

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207108497 233 PYVEIRQSTNVPQ-EGQYLKLQCVPKGNPSPDpVLWTKDGGELPDMDRMIVDGRDLTFTSLNKTDNGTYRCEATNHLGTS 311
Cdd:cd04968     1 PSIKVRFPADTYAlKGQTVTLECFALGNPVPQ-IKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKD 79

                  ....*....
gi 1207108497 312 HAEFKLVIY 320
Cdd:cd04968    80 TVQGRIIVQ 88

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207108497 151 ITLTCVTSGSkPAADVRWFKNEMEVKGAKEVnaSGKTFTVKSSLRLH-VNRDDDGVaYTCRVDHVALTATHEET 223
Cdd:cd00096     1 VTLTCSASGN-PPPTITWYKNGKPLPPSSRD--SRRSELGNGTLTISnVTLEDSGT-YTCVASNSAGGSASASV 70

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 1207108497 154 TCVTSGSKPAADVRWFKN-EMEVKGAKEVNASGKTFTVKSSLRLHVNRDDDGVAYTCRVDH 213
Cdd:cd07703    21 RCVSANGRPPARISWSSTlNGNANTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTCKVEH 81

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207108497 143 KPVLEGDHITLTCVTSG-SKPAADVRWFKNEMEV-KGAK---EVNASGKTFTVKSSLRLHVNRDDDGVAYTCRVDHVAL 216
Cdd:pfam07654   7 SPEELGKPNTLTCLVTGfYPPDITVTWLKNGQEVtEGVKttpPSPNSDWTYQLSSYLTVTPSDWESGDEYTCRVEHEGL 85

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207108497 247 GQYLKLQCVPKGNPSPDpVLWTKDGGELpdMDRMIVDGRDLTFT----SLNKTDNGTYRCEATNHLGTSHAEFKL 317
Cdd:cd05856    19 GSSVRLKCVASGNPRPD-ITWLKDNKPL--TPPEIGENKKKKWTlslkNLKPEDSGKYTCHVSNRAGEINATYKV 90

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 1207108497 235 VEIRQSTNVPQeGQYLKLQCVPKGNPSPDpVLWTKDGGEL------PDMDRMIVDGRDLTFTSL-----NKTDNGTYRCE 303
Cdd:cd07693     4 VEHPSDLIVSK-GDPATLNCKAEGRPTPT-IQWLKNGQPLetdkddPRSHRIVLPSGSLFFLRVvhgrkGRSDEGVYVCV 81

                  ....*...
gi 1207108497 304 ATNHLGTS 311
Cdd:cd07693    82 AHNSLGEA 89

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207108497  145 VLEGDHITLTCVTSGSkPAADVRWFKNEMEVKGAKEvNASGKTFTVKSSLRLH-VNRDDDGVaYTCRV 211
Cdd:smart00410   6 VKEGESVTLSCEASGS-PPPEVTWYKQGGKLLAESG-RFSVSRSGSTSTLTISnVTPEDSGT-YTCAA 70