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 12957496 170 PTVSLIKGPDSLIDGGNETVAAVCVAATGKPVAQIDWEGDLGEMESSTTSFPNETATIVSQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704   1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                        90
                ....*....|....*.
gi 12957496 250 HPALEKDIRYSFILDI 265
Cdd:cd07704  81 HPALQQDIRITHILDV 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496 170 PTVSLIKGPDSLIDGGNETVAAVCVAATGKPVAQIDWEGDLGEMESSTTSFPNETATIVSQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704   1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                        90
                ....*....|....*.
gi 12957496 250 HPALEKDIRYSFILDI 265
Cdd:cd07704  81 HPALQQDIRITHILDV 96

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 12957496 269 PEVSVTGYDGNWFVGRKGVNLKCNADANPPPFKSVWSRLDGQWPDGLLASDNTLhFVHPLTVNYSGVYVCKVSNSLGQRS 348
Cdd:cd20930   1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQL-LIHSVDRLVNTTFICTVTNAVGTGR 79

                ....*..
gi 12957496 349 DQKVIYI 355
Cdd:cd20930  80 AEQTIFV 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496     64 PHVTAVWGKNVSLKCLIEVNETItQISWEKIHGKstqtvaVHHPQYGFSVQGDYqgrvlfknyslNDATITLHNIGFSDS 143
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGK------LLAESGRFSVSRSG-----------STSTLTISNVTPEDS 63

                           90       100
                   ....*....|....*....|...
gi 12957496    144 GKYICkAVTFPLGNAQSSTTVTV 166
Cdd:smart00410  64 GTYTC-AATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 12957496   287 VNLKCNADANPPPfkSVWSRLDGQWPDGLLASDNTLHF------VHPLTVNYSGVYVCKVSN 342
Cdd:pfam13927  19 VTLTCEATGSPPP--TITWYKNGEPISSGSTRSRSLSGsnstltISNVTRSDAGTYTCVASN 78

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 12957496 170 PTVSLIKGPDSLIDGGNETVAAVCVAATGKPVAQIDWEGDLGEMESSTTSFPNETATIVSQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704   1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                        90
                ....*....|....*.
gi 12957496 250 HPALEKDIRYSFILDI 265
Cdd:cd07704  81 HPALQQDIRITHILDV 96

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 12957496 170 PTVSLIKGPDSLIdGGNETVAAVCVAATGKPVAQIDWEGDLGEMESSTTSFP-NETATIVSQYKLFPTRFARGRRITCVV 248
Cdd:cd05719   1 PTNSLEGGPALLI-GGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGsNGTVTVTSRYRLVPSREADGQPLTCVV 79

                        90
                ....*....|....*..
gi 12957496 249 KHPALEKDIRYSFILDI 265
Cdd:cd05719  80 EHPSLEKDQRISVTLNV 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 12957496  71 GKNVSLKCLIE---VNETITQISWEKIHGKSTQTVAVHHPQYGFSVQGDYQGRVLFKNYSLNDATITLHNIGFSDSGKYI 147
Cdd:cd05886  14 GTDVVLHCSFAnplPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLPPYRERVTFLNPSFTDGTIRLSRLELEDEGVYI 93

                        90       100
                ....*....|....*....|
gi 12957496 148 CKAVTFPLGNAQSSTTVTVL 167
Cdd:cd05886  94 CEFATFPTGNRESQLNLTVM 113

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 12957496  64 PHVTAVWGKNVSLKCLIEVNETITQISWEKIHGKStQTVAVHHPQYGFSVQGDYQGRVLFKNYSL--NDATITLHNIGFS 141
Cdd:cd05889   7 WDTSVPLSENMSLECVYPSTGILTQVEWTKIGGQK-DNIAVYHPTHGMHIRKPYAGRVYFLNSTMasNNMSLSFRNASED 85

                        90       100
                ....*....|....*....|....*....
gi 12957496 142 DSGKYICKAVTFPLGnaqSSTTVTVLVEP 170
Cdd:cd05889  86 DVGYYSCSLYTYPQG---SWEKVIQVVQS 111

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 12957496 269 PEVSVTGYDGNWFVGRKGVNLKCNADANPPPFKSVWSRLDGQWPDGLLASDNTLhFVHPLTVNYSGVYVCKVSNSLGQRS 348
Cdd:cd20930   1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQL-LIHSVDRLVNTTFICTVTNAVGTGR 79

                ....*..
gi 12957496 349 DQKVIYI 355
Cdd:cd20930  80 AEQTIFV 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 12957496  60 IIVEPHVTAVWGKNVSLKCLIEVNE---TITQISWEKiHGKStQTVAVHHPQYGFSVQGdyQGRVLF----KNYSLNDAT 132
Cdd:cd20989   3 VQVPPEVRGFLGGSVTLPCHLLPPNmvtHVSQVTWQR-HDEH-GSVAVFHPKQGPSFPE--SERLSFvaarLGAELRNAS 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 12957496 133 ITLHNIGFSDSGKYICKAVTFPLGNAQSSTTVTV 166
Cdd:cd20989  79 LAMFGLRVEDEGNYTCEFATFPQGSRSGDTWLRV 112

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 12957496 191 AVCVAATGKPVAQIDWEGDL-GEMESSTTSFPNETATIVSQYKLFPTRFARGRRITCVVKH 250
Cdd:cd05890  25 ATCTSANGKPPSVVSWDTRLkGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNY 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496     64 PHVTAVWGKNVSLKCLIEVNETItQISWEKIHGKstqtvaVHHPQYGFSVQGDYqgrvlfknyslNDATITLHNIGFSDS 143
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGK------LLAESGRFSVSRSG-----------STSTLTISNVTPEDS 63

                           90       100
                   ....*....|....*....|...
gi 12957496    144 GKYICkAVTFPLGNAQSSTTVTV 166
Cdd:smart00410  64 GTYTC-AATNSSGSASSGTTLTV 85

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 12957496  66 VTAVWGKNVSLKCLIEVNETI-----TQISWEKIHGKSTQTVAV------HHPQYGfsvqgDYQGRVLFKNYSLNDATIT 134
Cdd:cd05877   7 VFSHRGGNVTLPCRYHYEPELsaprkIRVKWTKLEVDYAKEEDVlvaigtRHKSYG-----SYQGRVFLRRADDLDASLV 81

                        90
                ....*....|....
gi 12957496 135 LHNIGFSDSGKYIC 148
Cdd:cd05877  82 ITDLRLEDYGRYRC 95

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 12957496 287 VNLKCNADANPPPfKSVWSR------LDGQWPDGLLASDNTLHFvHPLTVNYSGVYVCKVSNSLG 345
Cdd:cd00096   1 VTLTCSASGNPPP-TITWYKngkplpPSSRDSRRSELGNGTLTI-SNVTLEDSGTYTCVASNSAG 63

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 12957496 287 VNLKCNADANPPPfKSVWSRLDGQWPDGL--LASDNTLHFVHpLTVNYSGVYVCKVSNSLGQ 346
Cdd:cd05725  15 AEFQCEVGGDPVP-TVRWRKEDGELPKGRyeILDDHSLKIRK-VTAGDMGSYTCVAENMVGK 74

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496    62 VEPHVTAVW-GKNVSLKCLIEVNETITQISWEKIHGKSTQTVAVHHpqygfsvqgdyqgrvlfKNYSLNDATITLHNIGF 140
Cdd:pfam00047   1 SAPPTVTVLeGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKH-----------------DNGRTTQSSLLISNVTK 63

                          90       100
                  ....*....|....*....|....
gi 12957496   141 SDSGKYICKaVTFPLGNAQSSTTV 164
Cdd:pfam00047  64 EDAGTYTCV-VNNPGGSATLSTSL 86

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496     73 NVSLKCLIEVNE-TITQISW-EKIHGKSTQTVAVHHPQYGFSVQGDYQGRVLF-KNYSLNDATITLHNIGFSDSGKYICK 149
Cdd:smart00406   1 SVTLSCKFSGSTfSSYYVSWvRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTIsKDTSKNDVSLTISNLRVEDTGTYYCA 80

Immunoglobulin I-set domain;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 12957496   129 NDATITLHNIGFSDSGKYICKAvTFPLGNAQSSTTVTV 166
Cdd:pfam07679  54 GTYTLTISNVQPDDSGKYTCVA-TNSAGEAEASAELTV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496  65 HVTAVWGKNVSLKCLIEVNETiTQISWEKIHGkstQTVAVhhpqygfsvqGDYQG----RVLFKNYSLNDATITLHNIGF 140
Cdd:cd05717   5 DVTVVEGETLTLKCQVSLRDD-SSLQWLNPNG---QTIYF----------NDKRAlrdsRYQLLNHSASELSISVSNVTL 70

                        90       100
                ....*....|....*....|....*.
gi 12957496 141 SDSGKYICKAVTFPLgnAQSSTTVTV 166
Cdd:cd05717  71 SDEGVYTCLHYTDPV--STKKVTVTV 94

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496 167 LVEPTVSLIKGPDSLIDGGNEtVAAVCVAATGKPVAQIDWEGDLGEM--ESSTTSFPNETATIVSQYKLFPTRFARGRRI 244
Cdd:cd05883   1 LVPPRNLVIDIQKDTAVEGEE-IELNCTAMASKPAATIRWFKGNKELtgKSEVEEWYSRMFTVTSQLMLKVTKEDDGVPV 79

                        90
                ....*....|...
gi 12957496 245 TCVVKHPALeKDI 257
Cdd:cd05883  80 ICLVDHPAV-KDL 91

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 12957496 288 NLKCNADANPPPFKSvWSrldgqWPDGLLASDNTLhFVHPLTVNYSGVYVCKVSNSLGQRSDQKV 352
Cdd:cd20948  14 NLSCHAASNPPAQYS-WT-----INGTFQTSSQEL-FLPAITENNEGTYTCSAHNSLTGKNISLV 71

Tapasin-R immunoglobulin-like domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain on Tapasin-R. Tapasin is a V-C1 (variable-constant) immunoglobulin superfamily molecule present in the endoplasmic reticulum (ER), where it links MHC class I molecules to the transporter associated with antigen processing (TAP). Tapasin-R is a tapasin-related protein that contains similar structural motifs to Tapasin, with some marked differences, especially in the V domain, transmembrane and cytoplasmic regions. The majority of Tapasin-R is located within the ER; however, there may be some expression of Tapasin-R at the cell surface. Tapasin-R lacks an obvious ER retention signal.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 12957496 224 TATIVSQYKLFPTRFARGRRITCVVKHPALEKDIRYS 260
Cdd:cd05771  64 TYSISSYLTLEPGTENRGATYTCRVTHVSLEEPLSVS 100

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496  64 PHVTAVWGKNVSLKCLIEVNETIT---------QISWEKIH--GKSTQTVAVHHPQYG-FSVQGDYQGRVLFKNY--SLN 129
Cdd:cd05878   5 SPVRVLLGTSVTLPCYFIDPPHPVtpstaplapRIKWSKVSvdGKKEKEVVLLVATEGrVRVNSAYQGRVSLPNYpaIPS 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 12957496 130 DATITLHNIGFSDSGKYICKAVTfplGNAQSSTTVTVLVEPTV 172
Cdd:cd05878  85 DATLEVQSLRASDSGLYRCEVMH---GIEDSQDTVELVVKGVV 124

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12957496  66 VTAVWGKNVSLKCLIEVNETI---TQISW--EKIHGKSTQTVAVHHPQYGFSVQ-GDYQGRVLFK-NYSLNDATITLHNI 138
Cdd:cd05715   9 LNVLNGSDVRLTCTFTSCYTVgdaFSVTWtyQPEGGNTTESMFHYSKGKPYILKvGRFKDRVSWAgNPSKKDASIVISNL 88

                        90
                ....*....|
gi 12957496 139 GFSDSGKYIC 148
Cdd:cd05715  89 QFSDNGTYTC 98