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 209413728  29 VVVQAPTQVPGFLGDSVTLPCYLQVPNMeVTHVSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASL 108
Cdd:cd20989    1 VRVQVPPEVRGFLGGSVTLPCHLLPPNM-VTHVSQVTWQRHDEHGSVAVFHPKQGPSFPESERLSFVAARLGAELRNASL 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 209413728 109 RMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRV 141
Cdd:cd20989   80 AMFGLRVEDEGNYTCEFATFPQGSRSGDTWLRV 112

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728 244 PEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGPLPPFAVAQGAQLLIRPVDKPINTTLICNVTNALGARQA 323
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIHSVDRLVNTTFICTVTNAVGTGRA 80

                 ....*.
gi 209413728 324 ELTVQV 329
Cdd:cd20930   81 EQTIFV 86

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 209413728  29 VVVQAPTQVPGFLGDSVTLPCYLQVPNMeVTHVSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASL 108
Cdd:cd20989    1 VRVQVPPEVRGFLGGSVTLPCHLLPPNM-VTHVSQVTWQRHDEHGSVAVFHPKQGPSFPESERLSFVAARLGAELRNASL 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 209413728 109 RMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRV 141
Cdd:cd20989   80 AMFGLRVEDEGNYTCEFATFPQGSRSGDTWLRV 112

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 209413728 244 PEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGPLPPFAVAQGAQLLIRPVDKPINTTLICNVTNALGARQA 323
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIHSVDRLVNTTFICTVTNAVGTGRA 80

                 ....*.
gi 209413728 324 ELTVQV 329
Cdd:cd20930   81 EQTIFV 86

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728    44 SVTLPC-YLQVPNMEvthvSQLTWARH--GESGSMAVFHQTQGPSYSESK---RLEFVAARLGaelRNASLRMFGLRVED 117
Cdd:smart00406   1 SVTLSCkFSGSTFSS----YYVSWVRQppGKGLEWLGYIGSNGSSYYQESykgRFTISKDTSK---NDVSLTISNLRVED 73

                   ....*...
gi 209413728   118 EGNYTCLF 125
Cdd:smart00406  74 TGTYYCAV 81

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 209413728  29 VVVQAPTQVPGFLGDSVTLPCYLQVPNMeVTHVSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASL 108
Cdd:cd20989    1 VRVQVPPEVRGFLGGSVTLPCHLLPPNM-VTHVSQVTWQRHDEHGSVAVFHPKQGPSFPESERLSFVAARLGAELRNASL 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 209413728 109 RMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRV 141
Cdd:cd20989   80 AMFGLRVEDEGNYTCEFATFPQGSRSGDTWLRV 112

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 209413728 244 PEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGPLPPFAVAQGAQLLIRPVDKPINTTLICNVTNALGARQA 323
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQLLIHSVDRLVNTTFICTVTNAVGTGRA 80

                 ....*.
gi 209413728 324 ELTVQV 329
Cdd:cd20930   81 EQTIFV 86

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 209413728 145 PQNTAEVQKVQL-TGEPVPMARCVSTGGRPPAQITWHSDLGGMPNTSQVPGFlSGTVTVTSLWILVPSSQVDGKNVTCKV 223
Cdd:cd05719    1 PTNSLEGGPALLiGGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGS-NGTVTVTSRYRLVPSREADGQPLTCVV 79

                         90
                 ....*....|....*..
gi 209413728 224 EHESFEKPQLLTVNLTV 240
Cdd:cd05719   80 EHPSLEKDQRISVTLNV 96

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 209413728 164 ARCVSTGGRPPAQITWHSDLGGMPNTSQVpgFLSGTVTVTSLWILVPSSQVDGKNVTCKVEHESFEKPQLLTVNLTV 240
Cdd:cd07704   22 ASCTAETGKPAASVTWETDLGGMESSRTF--EHNRTATVTSEYHLVPTRFANGRPLTCVVSHPALQQDIRITHILDV 96

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-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. In addition nectins 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 209413728  30 VVQAPTQVPGFLGDSVTLPCYLQVPNMEVThVSQLTWAR--HGESGSMAVFHQTQG----PSYSEskRLEFvaarLGAEL 103
Cdd:cd05886    2 TVQVNDSMSGFIGTDVVLHCSFANPLPSVK-ITQVTWQKstNGSKQNVAIYNPSMGvsvlPPYRE--RVTF----LNPSF 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 209413728 104 RNASLRMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRVL 142
Cdd:cd05886   75 TDGTIRLSRLELEDEGVYICEFATFPTGNRESQLNLTVM 113

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728  41 LGDSVTLPCYLQVPNMEvtHVSQLTWARHGESG---SMAVFH----QTQGPSYSesKRLEFVA----ARLGAELRNASlr 109
Cdd:cd05888    7 LGQDAKLPCFYRGDSGE--QVGQVAWARVDAGEgaqEIALLHskygLHVFPAYE--GRVEQPPpprpADGSVLLRNAV-- 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 209413728 110 mfglrVEDEGNYTCLFVTFPQGSRSVDIWLRVL 142
Cdd:cd05888   81 -----QADEGEYECRVSTFPAGNFQAELRLRVL 108

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728    44 SVTLPC-YLQVPNMEvthvSQLTWARH--GESGSMAVFHQTQGPSYSESK---RLEFVAARLGaelRNASLRMFGLRVED 117
Cdd:smart00406   1 SVTLSCkFSGSTFSS----YYVSWVRQppGKGLEWLGYIGSNGSSYYQESykgRFTISKDTSK---NDVSLTISNLRVED 73

                   ....*...
gi 209413728   118 EGNYTCLF 125
Cdd:smart00406  74 TGTYYCAV 81

First immunoglobulin variable (IgV) domain of DNAX accessory molecule 1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of DNAX accessory molecule 1 (DNAM-1, also known as CD226). DNAM-1 is a transmembrane protein having two Ig-like domains. It is an adhesion molecule which plays a part in tumor-directed cytotoxicity and adhesion in natural killer (NK) cells and T lymphocytes. It has been shown to regulate the NK cell killing of several tumor types, including myeloma cells and ovarian carcinoma cells. DNAM-1 interacts specifically with poliovirus receptor (PVR; CD155) and nectin -2 (CD211), other members of the Ig superfamily. DNAM-1 is expressed in most peripheral T cells, NK cells, monocytes and a subset of B lymphocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728  41 LGDSVTLPCYlqVPNMEVthVSQLTWARH-GESGSMAVFHQTQG----PSYSEskRLEFVAARLGAelRNASLRMFGLRV 115
Cdd:cd05889   13 LSENMSLECV--YPSTGI--LTQVEWTKIgGQKDNIAVYHPTHGmhirKPYAG--RVYFLNSTMAS--NNMSLSFRNASE 84

                         90       100
                 ....*....|....*....|..
gi 209413728 116 EDEGNYTCLFVTFPQGSRSVDI 137
Cdd:cd05889   85 DDVGYYSCSLYTYPQGSWEKVI 106

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728  27 GDVVVqaPTQVPGFLGDSVTLPCYLQVPnmevTHVSQLTWAR-HGESG-SMAVFHQTQGPSYSE--SKRLEFVAArlgaE 102
Cdd:cd05887    1 GPIIV--EPHVTAVWGKNVSLKCLIEVN----ETITQISWEKiHGKSSqTVAVHHPQYGISIQGeyQGRVSFKNY----S 70

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 209413728 103 LRNASLRMFGLRVEDEGNYTCLFVTFPQGSRSVDIWLRVL 142
Cdd:cd05887   71 LNDATITLHNVGFSDSGKYICKAVTFPLGNAQSSTTVTVL 110

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 209413728 150 EVQKVQLTgepvpmarCVSTGGRPPAQITW---HSDLGGMPNTSQVPGflSGTVTVTSLWILVPSSQVDGKNVTCKVEHE 226
Cdd:cd05761   18 EGDEITLT--------CTTSGSKPAADIRWfknDKELKGVKEVQESGA--GKTFTVTSTLRFRVDRDDDGVAVICRVDHE 87

                 .
gi 209413728 227 S 227
Cdd:cd05761   88 S 88

N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family and similar proteins. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. Members of this group include proteins such as CD84, SLAM (CD150), Ly-9 (CD229), NTB-A (ly-108, SLAM6), 19A (CRACC), and SLAMF9. The genes coding for the SLAM family are nested on chromosome 1, in humans at 1q23, and in mice at 1H2. The SLAM family is a subset of the CD2 family, which also includes CD2 and CD58 located on chromosome 1 at 1p13 in humans. In mice, CD2 is located on chromosome 3, and there is no CD58 homolog. The SLAM family proteins are organized as an extracellular domain with either two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728  35 TQVPGFLGDSVTLPcyLQVPnmEVTHVSQLTWARH--------GESGSmAVFHQTQgPSYSEskRLEFVAarlgaelRNA 106
Cdd:cd16842    1 KEVNGILGGSVTFP--LNIS--DGQEIENITWSFKtslaviapGEGGA-PEIIITD-KSYKE--RLNISQ-------NDY 65

                         90
                 ....*....|....*
gi 209413728 107 SLRMFGLRVEDEGNY 121
Cdd:cd16842   66 SLQISNLTMEDAGSY 80

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209413728  33 APTQVPGFLGDSVTLPC-YLQVPNMEVTHVSQLTWARHGESG--------SMAVFHQTQGpSYSESKRLEfvaarlGAEL 103
Cdd:cd05877    3 VQAKVFSHRGGNVTLPCrYHYEPELSAPRKIRVKWTKLEVDYakeedvlvAIGTRHKSYG-SYQGRVFLR------RADD 75

                         90       100
                 ....*....|....*....|
gi 209413728 104 RNASLRMFGLRVEDEGNYTC 123
Cdd:cd05877   76 LDASLVITDLRLEDYGRYRC 95