Second immunoglobulin (Ig) domain of nectin-1, 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-1 (also known as poliovirus receptor related protein 1, or cluster of differentiation (CD) 111). Nectin-1 belongs 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. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 146 PTNWIEGTRAVLRARKGQDDKVLVATCTSANGKPPSAVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 148693609 226 CIVNYHLDRFRESLTLNV 243
Cdd:cd05890   81 CIVNYHMDRFTDSLTLNV 98

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                         10        20        30
                 ....*....|....*....|....*....|
gi 148693609 353 TAIIGGVAGSVLLVLIVvgGIIVALRRRRH 382
Cdd:cd12087    6 TSIAAGVVGGLLVLVIL--GLIVFLFRRRR 33

Second immunoglobulin (Ig) domain of nectin-1, 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-1 (also known as poliovirus receptor related protein 1, or cluster of differentiation (CD) 111). Nectin-1 belongs 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. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 146 PTNWIEGTRAVLRARKGQDDKVLVATCTSANGKPPSAVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 148693609 226 CIVNYHLDRFRESLTLNV 243
Cdd:cd05890   81 CIVNYHMDRFTDSLTLNV 98

Third immunoglobulin domain of Nectin-like Protein-5, and similar domains; The members here are composed of the third immunoglobulin domain of Nectin-like Protein-5 (also known as Cluster of Differentiation 155 (CD155)). Nectin-like Protein-5 mediates NK (Natural Killer) cell adhesion and triggers NK cell effector functions. CD155 binds two different NK cell receptors: CD96 and CD226. These interactions accumulate at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. CD155 may also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Moreover, CD155 plays a role in mediating tumor cell invasion and migration.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 247 PEVTIEGFDGNWYLQRTDVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTLFFRgPITYSLAGTYICEATNPIGTrs 326
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIH-SVDRLVNTTFICTVTNAVGT-- 77

                 ....*..
gi 148693609 327 GQVEVNI 333
Cdd:cd20930   78 GRAEQTI 84

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609    46 DVVLHCSFANPLPSvkITQVTWQKASNGSKQNMAIYNPTMGVSVLPP-YEKRVEFLR-PSFIDGTIRLSGLELEDEGMYI 123
Cdd:smart00406   1 SVTLSCKFSGSTFS--SYYVSWVRQPPGKGLEWLGYIGSNGSSYYQEsYKGRFTISKdTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 148693609   124 CEF 126
Cdd:smart00406  79 CAV 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148693609  264 DVKLTCKADANPPATeYHWTtLNGSLPKGVEAQ-------NRTLFFRgPITYSLAGTYICEATN 320
Cdd:pfam13927  18 TVTLTCEATGSPPPT-ITWY-KNGEPISSGSTRsrslsgsNSTLTIS-NVTRSDAGTYTCVASN 78

Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. They are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of EGFR family RTKs have been associated with increased breast cancer risk.

                         10        20        30
                 ....*....|....*....|....*....|
gi 148693609 353 TAIIGGVAGSVLLVLIVvgGIIVALRRRRH 382
Cdd:cd12087    6 TSIAAGVVGGLLVLVIL--GLIVFLFRRRR 33

Second immunoglobulin (Ig) domain of nectin-1, 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-1 (also known as poliovirus receptor related protein 1, or cluster of differentiation (CD) 111). Nectin-1 belongs 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. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 146 PTNWIEGTRAVLRARKGQDDKVLVATCTSANGKPPSAVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 148693609 226 CIVNYHLDRFRESLTLNV 243
Cdd:cd05890   81 CIVNYHMDRFTDSLTLNV 98

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 148693609 146 PTNWIEGTRAVLRarkgQDDKVLVATCTSANGKPPSAVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05719    1 PTNSLEGGPALLI----GGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLT 76

                         90       100
                 ....*....|....*....|
gi 148693609 226 CIVNYH--LDRFRESLTLNV 243
Cdd:cd05719   77 CVVEHPslEKDQRISVTLNV 96

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609  44 GTDVVLHCSFANPLpsvKITQVTWQKASNGSKQNMAIYNPTMGVSVLPPYEKRVEFLRPSFIDGTIRLSGLELEDEGMYI 123
Cdd:cd05846   13 GGNATLSCNLTLPE---EVLQVTWQKIKASSPENIVTYSKKYGVKIQPSYVRRISFTSSGLNSTSITIWNVTLEDEGCYK 89

                         90
                 ....*....|....*....
gi 148693609 124 CEFATFPTGNRESQLNLTV 142
Cdd:cd05846   90 CLFNTFPDGIKSGTACLTV 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609  148 NWIEGTRAVLRArkgqDDKVLVATCTSANGKPPSAVSWETRLKGE---AEYQEIRNPNGTVTVISRYRLVPSREAHRQSL 224
Cdd:pfam08205   1 PTIEPPASLLEG----EGPEVVATCSSAGGKPAPRITWYLDGKPLeaaETSSEQDPESGLVTVTSELKLVPSRSDHGQSL 76

                          90
                  ....*....|..
gi 148693609  225 ACIVNYHLDRFR 236
Cdd:pfam08205  77 TCQVSYGALRGS 88

Third immunoglobulin domain of Nectin-like Protein-5, and similar domains; The members here are composed of the third immunoglobulin domain of Nectin-like Protein-5 (also known as Cluster of Differentiation 155 (CD155)). Nectin-like Protein-5 mediates NK (Natural Killer) cell adhesion and triggers NK cell effector functions. CD155 binds two different NK cell receptors: CD96 and CD226. These interactions accumulate at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. CD155 may also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Moreover, CD155 plays a role in mediating tumor cell invasion and migration.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 247 PEVTIEGFDGNWYLQRTDVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTLFFRgPITYSLAGTYICEATNPIGTrs 326
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIH-SVDRLVNTTFICTVTNAVGT-- 77

                 ....*..
gi 148693609 327 GQVEVNI 333
Cdd:cd20930   78 GRAEQTI 84

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609 166 KVLVATCTSANGKPPSAVSWETRLKGEAEYQEIRnPNGTVTVISRYRLVPSREAHRQSLACIVNYH--LDRFRESLTLNV 243
Cdd:cd07704   18 ETLAASCTAETGKPAASVTWETDLGGMESSRTFE-HNRTATVTSEYHLVPTRFANGRPLTCVVSHPalQQDIRITHILDV 96

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 148693609   44 GTDVVLHCSFaNPLPSVKITQVTW--QKASNGSKQNMAIYNPTMGVSVLPPyekRVEFLR-PSFIDGTIRLSGLELEDEG 120
Cdd:pfam07686  11 GGSVTLPCTY-SSSMSEASTSVYWyrQPPGKGPTFLIAYYSNGSEEGVKKG---RFSGRGdPSNGDGSLTIQNLTLSDSG 86

                          90       100
                  ....*....|....*....|..
gi 148693609  121 MYICEFATFPTGNRESQLNLTV 142
Cdd:pfam07686  87 TYTCAVIPSGEGVFGKGTRLTV 108

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609  32 VVQVNDSMYGFIGTDVVLHCSFANPLPSVKITQVTW--QKASNGSKQNMAIY-NPTMGVSVLPPYEKRVEFL-RPSFIDG 107
Cdd:cd05715    2 EVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWtyQPEGGNTTESMFHYsKGKPYILKVGRFKDRVSWAgNPSKKDA 81

                         90
                 ....*....|....*..
gi 148693609 108 TIRLSGLELEDEGMYIC 124
Cdd:cd05715   82 SIVISNLQFSDNGTYTC 98

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 148693609 265 VKLTCkaDANPPATEYHWTTLNGSLPKGVEAQ----NRTLFFRgPITYSLAGTYICEATNPIGT-RSGQVEVNI 333
Cdd:cd05740   18 VTLTC--EPETQNTSYLWWFNGQSLPVTPRLTlsngNRTLTLL-NVTREDAGAYQCEISNPVSAnRSDPVTLDV 88

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148693609 265 VKLTCKADANPPATeYHWTTLNGSLPKGVEAQNR------TLFFRgPITYSLAGTYICEATNPIGTRS 326
Cdd:cd00096    1 VTLTCSASGNPPPT-ITWYKNGKPLPPSSRDSRRselgngTLTIS-NVTLEDSGTYTCVASNSAGGSA 66

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609  38 SMYGFIGTDVVLHCSfANPLpsvKITQVTWQKasngSKQNMAIYNPTMGVSVLPPYEKRVEFLrpsFIDGTIRLSGLELE 117
Cdd:cd05775    4 EVYGALGGNVTLTIS-SLQD---DIDEIKWKK----TKDKIVEWENNIGPTYFGSFKDRVLLD---KESGSLTIKNLTKE 72

                         90       100
                 ....*....|....*....|....*
gi 148693609 118 DEGMYICEFATFPTGNRESQLNLTV 142
Cdd:cd05775   73 DSGTYELEITSTNGKVLSSKFTLEV 97

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 148693609 264 DVKLTCKADAnPPATEYHWTTLNGSLPKG---VEAQNRTLFFRGpITYSLAGTYICEATNPIGTRSGQVEV 331
Cdd:cd05731   12 VLLLECIAEG-LPTPDIRWIKLGGELPKGrtkFENFNKTLKIEN-VSEADSGEYQCTASNTMGSARHTISV 80

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148693609 265 VKLTCKADANPPATeYHWTTLNGSLPKGVEAQNR----TLFFRGPITYSLAGTYICEATNPIGT 324
Cdd:cd04967   22 VALNCRARANPVPS-YRWLMNGTEIDLESDYRYSlvdgTLVISNPSKAKDAGHYQCLATNTVGS 84

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 148693609 259 YLQRTDVKLTCKADANPPAtEYHWTTlNGslpkGVEAQNRTLFFrGPITYSLAGTYICEATNPIGTRS 326
Cdd:cd20948    7 YLSGENLNLSCHAASNPPA-QYSWTI-NG----TFQTSSQELFL-PAITENNEGTYTCSAHNSLTGKN 67

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 148693609  261 QRTDVKLTCKADANPPATeYHWTTLNGSLPKGveaQNrtlFFRGPITYSLAGTYICEATNP-IGTRSGQVEVNI 333
Cdd:pfam13895  13 EGEPVTLTCSAPGNPPPS-YTWYKDGSAISSS---PN---FFTLSVSAEDSGTYTCVARNGrGGKVSNPVELTV 79

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 148693609 171 TCTSANGKPPSAVSW---ETRLKGEAEYQEiRNPNGTVTVISRYRLVPSREAHRQSLACIVNYhldrfrESLT 240
Cdd:cd05761   25 TCTTSGSKPAADIRWfknDKELKGVKEVQE-SGAGKTFTVTSTLRFRVDRDDDGVAVICRVDH------ESLT 90

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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 148693609 258 WYLQRTDVKLTCKADANPpATEYHWTTLNGSLpkgVEAQNRTLFFR------GPITYSLAGTYICEATNPIGTRSGQVEV 331
Cdd:cd05764   11 RVLEGQRATLRCKARGDP-EPAIHWISPEGKL---ISNSSRTLVYDngtldiLITTVKDTGAFTCIASNPAGEATARVEL 86

                 ..
gi 148693609 332 NI 333
Cdd:cd05764   87 HI 88

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 148693609 264 DVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTLFFRgPITYSLAGTYICEATNPIGTRSG 327
Cdd:cd05754   18 DVSFICRAKSKSPAYTLVWTRVNGTLPSRAMDFNGILTIR-NVQLSDAGTYVCTGSNMLDTDEA 80

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148693609  46 DVVLHCSFaNPLPSVKITqvtWQKASNGSKQNMAIYNPTMGVSVLPPYEKRVEFLRPSFIDG--TIRLSGLELEDEGMYI 123
Cdd:cd16091   14 DCILPCSF-TPGSEVVIH---WYKQDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGnaSLLLRRVQLQDEGRYK 89

                         90
                 ....*....|....*....
gi 148693609 124 CEFATFpTGNRESQLNLTV 142
Cdd:cd16091   90 CYTSTI-IGNQESFVNLKV 107