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 747165386 146 PTNWIEGTQAVLRARKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 747165386 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 747165386 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 747165386 146 PTNWIEGTQAVLRARKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 747165386 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 747165386 247 PEVTIEGFDGNWYLQRTDVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTLFFRgPINYSLAGTYICEATNPIGTrs 326
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIH-SVDRLVNTTFICTVTNAVGT-- 77

                 ....*..
gi 747165386 327 GQVEVNI 333
Cdd:cd20930   78 GRAEQTI 84

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386    46 DVILHCSFANPlpTVKITQVTWQKASNGSKQNMAIYNPTMGVSVLPP-YEKRVEFLR-PSFIDGTIRLSHLELEDEGMYI 123
Cdd:smart00406   1 SVTLSCKFSGS--TFSSYYVSWVRQPPGKGLEWLGYIGSNGSSYYQEsYKGRFTISKdTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 747165386   124 CEF 126
Cdd:smart00406  79 CAV 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 747165386  264 DVKLTCKADANPPATeYHWTtLNGSLPKGVEAQ-------NRTLFFRgPINYSLAGTYICEATN 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 747165386 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 747165386 146 PTNWIEGTQAVLRARKGQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05890    1 PTNRMEGTTAVLRAKKGQDDKVLVATCTSANGKPPSVVSWDTRLKGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLA 80

                         90
                 ....*....|....*...
gi 747165386 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 747165386 146 PTNWIEGTQAVLRarkgQDDKVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRNPNGTVTVISRYRLVPSREAHRQSLA 225
Cdd:cd05719    1 PTNSLEGGPALLI----GGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGSNGTVTVTSRYRLVPSREADGQPLT 76

                         90       100
                 ....*....|....*....|
gi 747165386 226 CIVNYH--LDRFRESLTLNV 243
Cdd:cd05719   77 CVVEHPslEKDQRISVTLNV 96

First immunoglobulin variable (IgV) domain of nectin-2, nectin-like protein 5, and similar 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386  32 VVQVNDSMYGFIGTDVILHCSFANPLPTVKITQVTWQKASNGskQNMAIYNPTMGVSVlpPYEKRVEFLRP----SFIDG 107
Cdd:cd20989    2 RVQVPPEVRGFLGGSVTLPCHLLPPNMVTHVSQVTWQRHDEH--GSVAVFHPKQGPSF--PESERLSFVAArlgaELRNA 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 747165386 108 TIRLSHLELEDEGMYICEFATFPTGNRESQLNLTV 142
Cdd:cd20989   78 SLAMFGLRVEDEGNYTCEFATFPQGSRSGDTWLRV 112

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386 164 DDKVLVATCTSANGKPPSVVSWETRLKGEA-EYQEIRNPNGTVTVISRYRLVPSREAHRQSLACIVNYhlDRFRE----S 238
Cdd:cd07703   14 GIPVPVARCVSANGRPPARISWSSTLNGNAnTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTCKVEH--ETLEEpqllP 91

                 ....*.
gi 747165386 239 LTLNVQ 244
Cdd:cd07703   92 VTLSVR 97

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 747165386 247 PEVTIEGFDGNWYLQRTDVKLTCKADANPPATEYHWTTLNGSLPKGVEAQNRTLFFRgPINYSLAGTYICEATNPIGTrs 326
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIH-SVDRLVNTTFICTVTNAVGT-- 77

                 ....*..
gi 747165386 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 747165386 166 KVLVATCTSANGKPPSVVSWETRLKGEAEYQEIRnPNGTVTVISRYRLVPSREAHRQSLACIVNYH--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 747165386   44 GTDVILHCSFaNPLPTVKITQVTW--QKASNGSKQNMAIYNPTMGVSVLPPyekRVEFLR-PSFIDGTIRLSHLELEDEG 120
Cdd:pfam07686  11 GGSVTLPCTY-SSSMSEASTSVYWyrQPPGKGPTFLIAYYSNGSEEGVKKG---RFSGRGdPSNGDGSLTIQNLTLSDSG 86

                          90       100
                  ....*....|....*....|..
gi 747165386  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 747165386  32 VVQVNDSMYGFIGTDVILHCSFANPLPTVKITQVTW--QKASNGSKQNMAIY-NPTMGVSVLPPYEKRVEFL-RPSFIDG 107
Cdd:cd05715    2 EVYTPRELNVLNGSDVRLTCTFTSCYTVGDAFSVTWtyQPEGGNTTESMFHYsKGKPYILKVGRFKDRVSWAgNPSKKDA 81

                         90
                 ....*....|....*..
gi 747165386 108 TIRLSHLELEDEGMYIC 124
Cdd:cd05715   82 SIVISNLQFSDNGTYTC 98

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386    46 DVILHCSFANPlpTVKITQVTWQKASNGSKQNMAIYNPTMGVSVLPP-YEKRVEFLR-PSFIDGTIRLSHLELEDEGMYI 123
Cdd:smart00406   1 SVTLSCKFSGS--TFSSYYVSWVRQPPGKGLEWLGYIGSNGSSYYQEsYKGRFTISKdTSKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 747165386   124 CEF 126
Cdd:smart00406  79 CAV 81

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 747165386 265 VKLTCkaDANPPATEYHWTTLNGSLPKGVEAQ----NRTLFFRgPINYSLAGTYICEATNPIGT-RSGQVEVNI 333
Cdd:cd05740   18 VTLTC--EPETQNTSYLWWFNGQSLPVTPRLTlsngNRTLTLL-NVTREDAGAYQCEISNPVSAnRSDPVTLDV 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386    38 SMYGFIGTDVILHCSFANPLPTvkitQVTWQKasNGSKqnmaiynptmgvsvLPPYEKRVEFLRPSFiDGTIRLSHLELE 117
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPP----EVTWYK--QGGK--------------LLAESGRFSVSRSGS-TSTLTISNVTPE 61

                           90       100
                   ....*....|....*....|....*
gi 747165386   118 DEGMYICEfATFPTGNRESQLNLTV 142
Cdd:smart00410  62 DSGTYTCA-ATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 747165386  264 DVKLTCKADANPPATeYHWTtLNGSLPKGVEAQ-------NRTLFFRgPINYSLAGTYICEATN 320
Cdd:pfam13927  18 TVTLTCEATGSPPPT-ITWY-KNGEPISSGSTRsrslsgsNSTLTIS-NVTRSDAGTYTCVASN 78

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 747165386  44 GTDVILHCSfANPLPTvkiTQVTWQKASnGSKQNM---AIYNPTmgVSVLPpyekrveflrpsfiDGTIRLSHLELEDEG 120
Cdd:cd20954   16 GQDVMLHCQ-ADGFPT---PTVTWKKAT-GSTPGEykdLLYDPN--VRILP--------------NGTLVFGHVQKENEG 74

                 ....*
gi 747165386 121 MYICE 125
Cdd:cd20954   75 HYLCE 79

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 747165386 264 DVKLTCKADAnPPATEYHWTTLNGSLPKG---VEAQNRTLFFRGpINYSLAGTYICEATNPIGTRSGQVEV 331
Cdd:cd05731   12 VLLLECIAEG-LPTPDIRWIKLGGELPKGrtkFENFNKTLKIEN-VSEADSGEYQCTASNTMGSARHTISV 80

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 747165386 171 TCTSANGKPPSVVSW---ETRLKGEAEYQEiRNPNGTVTVISRYRLVPSREAHRQSLACIVNYhldrfrESLT 240
Cdd:cd05761   25 TCTTSGSKPAADIRWfknDKELKGVKEVQE-SGAGKTFTVTSTLRFRVDRDDDGVAVICRVDH------ESLT 90

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.

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gi 747165386 353 TAIIGGVAGSVLLVLIVvgGIIVALRRRRH 382
Cdd:cd12087    6 TSIAAGVVGGLLVLVIL--GLIVFLFRRRR 33

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 747165386  260 LQRTDVKLTCKADANPPATEYHW-----TTLNGSLPKGVEAQNRTL-FFRGPINYSLAGTYICEATNPIG 323
Cdd:pfam00047   9 LEGDSATLTCSASTGSPGPDVTWskeggTLIESLKVKHDNGRTTQSsLLISNVTKEDAGTYTCVVNNPGG 78

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 747165386 258 WYLQRTDVKLTCKADANPpATEYHWTTLNGSLpkgVEAQNRTLFFRgpiNYSL---------AGTYICEATNPIGTRSGQ 328
Cdd:cd05764   11 RVLEGQRATLRCKARGDP-EPAIHWISPEGKL---ISNSSRTLVYD---NGTLdilittvkdTGAFTCIASNPAGEATAR 83

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gi 747165386 329 VEVNI 333
Cdd:cd05764   84 VELHI 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.

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gi 747165386  47 VILHCSF-ANPLPTVkitqvTWQKasNGSKQNMAIYNPTMGVSVlppyekrveflrpsfiDGTIRLSHLELEDEGMYICE 125
Cdd:cd00096    1 VTLTCSAsGNPPPTI-----TWYK--NGKPLPPSSRDSRRSELG----------------NGTLTISNVTLEDSGTYTCV 57

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

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gi 747165386  37 DSMYGFIGTDVILHCSFAnPLPTVKITQVT--WQKasngSKQNMAIYNPTMGVSVL----PPYEKRVEFLRPSFIDG--T 108
Cdd:cd20934    5 DPVVALVGTDATLRCSFS-PEPGFSLAQLSvfWQL----TDTKQLVHSFTESQDQGrdqgSAYANRTALFPDLLAQGnaS 79

                         90
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gi 747165386 109 IRLSHLELEDEGMYIC 124
Cdd:cd20934   80 LRLQRVRVADEGSYTC 95