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 109032960 170 PTVSLIKGPDSLIDGGNETVAAICIAATGKPVAHIDWEGDLGEMESTTTSFPNETATIISQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704    1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                         90
                 ....*....|....*.
gi 109032960 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 109032960 170 PTVSLIKGPDSLIDGGNETVAAICIAATGKPVAHIDWEGDLGEMESTTTSFPNETATIISQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704    1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                         90
                 ....*....|....*.
gi 109032960 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 109032960 269 PEVSVTGYDGNWFVGRKGVNLKCNADANPPPFKSVWSRLDGQWPDGLLASDNTLhFVHPLTFNYSGVYICKVTNSLGQRS 348
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQL-LIHSVDRLVNTTFICTVTNAVGTGR 79

                 ....*..
gi 109032960 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 109032960    64 PHVTAVWGKNVSLKCLIEVNETItQISWEKIHGKSSQtvavhhpqygfsvqgeYQGRVLFKNYSlNDATITLHNIGFSDS 143
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKLLA----------------ESGRFSVSRSG-STSTLTISNVTPEDS 63

                           90       100
                   ....*....|....*....|...
gi 109032960   144 GKYICkAVTFPLGNAQSSTTVTV 166
Cdd:smart00410  64 GTYTC-AATNSSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 109032960  287 VNLKCNADANPPPfKSVWSRlDGQwpdgLLASDNTLHF----------VHPLTFNYSGVYICKVTNSLGQRS 348
Cdd:pfam07679  18 ARFTCTVTGTPDP-EVSWFK-DGQ----PLRSSDRFKVtyeggtytltISNVQPDDSGKYTCVATNSAGEAE 83

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 109032960 170 PTVSLIKGPDSLIDGGNETVAAICIAATGKPVAHIDWEGDLGEMESTTTSFPNETATIISQYKLFPTRFARGRRITCVVK 249
Cdd:cd07704    1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                         90
                 ....*....|....*.
gi 109032960 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 109032960 170 PTVSLIKGPDSLIdGGNETVAAICIAATGKPVAHIDWEGDLGEMESTTTSFP-NETATIISQYKLFPTRFARGRRITCVV 248
Cdd:cd05719    1 PTNSLEGGPALLI-GGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGsNGTVTVTSRYRLVPSREADGQPLTCVV 79

                         90
                 ....*....|....*..
gi 109032960 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 109032960  71 GKNVSLKCLI---EVNETITQISWEKIHGKSSQTVAVHHPQYGFSVQGEYQGRVLFKNYSLNDATITLHNIGFSDSGKYI 147
Cdd:cd05886   14 GTDVVLHCSFanpLPSVKITQVTWQKSTNGSKQNVAIYNPSMGVSVLPPYRERVTFLNPSFTDGTIRLSRLELEDEGVYI 93

                         90       100
                 ....*....|....*....|
gi 109032960 148 CKAVTFPLGNAQSSTTVTVL 167
Cdd:cd05886   94 CEFATFPTGNRESQLNLTVM 113

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 109032960 269 PEVSVTGYDGNWFVGRKGVNLKCNADANPPPFKSVWSRLDGQWPDGLLASDNTLhFVHPLTFNYSGVYICKVTNSLGQRS 348
Cdd:cd20930    1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQL-LIHSVDRLVNTTFICTVTNAVGTGR 79

                 ....*..
gi 109032960 349 DQKVIYI 355
Cdd:cd20930   80 AEQTIFV 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 109032960 184 GGNETVAAICIAATGKPVAHIDWEGDLGEMESTT--TSFPNETATIISQYKLFPTRFARGRRITCVVKHPALEKD 256
Cdd:cd07703   13 GGIPVPVARCVSANGRPPARISWSSTLNGNANTTqvPGPDSGTVTVTSEYSLVPTPEANGKEVTCKVEHETLEEP 87

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 109032960  60 IIVEPHVTAVWGKNVSLKCLIEVNE---TITQISWEKiHGkSSQTVAVHHPQYGFSVQGEyqGRVLF----KNYSLNDAT 132
Cdd:cd20989    3 VQVPPEVRGFLGGSVTLPCHLLPPNmvtHVSQVTWQR-HD-EHGSVAVFHPKQGPSFPES--ERLSFvaarLGAELRNAS 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 109032960 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 109032960 191 AICIAATGKPVAHIDWEGDL-GEMESTTTSFPNETATIISQYKLFPTRFARGRRITCVVKH 250
Cdd:cd05890   25 ATCTSANGKPPSVVSWDTRLkGEAEFQEIRNPNGTVTVISRYRLVPSREAHQQSLACIVNY 85

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960  63 EPHVTAVWGKNVSLKCLIEVNETITQISWEKIHGksSQTVAVHHPQygfSVQGEYQGRVlfknySLNDATITLHNIGFSD 142
Cdd:cd20946    6 QQVVTVVENQEVILSCKTPKKTSSPRVEWKKLQR--DVTFVVFQNN---KIQGDYKGRA-----EILGTNITIKNVTRSD 75

                         90       100
                 ....*....|....*....|....*.
gi 109032960 143 SGKYICKAVTFPLGNAQSSTTVTVLV 168
Cdd:cd20946   76 SGKYRCEVSARSDGQNLGEVTVTLEV 101

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 109032960  66 VTAVWGKNVSLKCLIEVNETI-----TQISWEKIHGKSSQTVAV------HHPQYGfsvqgEYQGRVLFKNYSLNDATIT 134
Cdd:cd05877    7 VFSHRGGNVTLPCRYHYEPELsaprkIRVKWTKLEVDYAKEEDVlvaigtRHKSYG-----SYQGRVFLRRADDLDASLV 81

                         90
                 ....*....|....
gi 109032960 135 LHNIGFSDSGKYIC 148
Cdd:cd05877   82 ITDLRLEDYGRYRC 95

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960 171 TVSLIKGPDSLIDGGNETVaaICIAaTG--KPVAHIDWEGDLGEMESTTTSFP-----NETATIISQYKLFPTRFARGRR 243
Cdd:cd00098    1 TVTLLPPSPEEKGGGKVTL--VCLV-SGfyPKDITVTWLKNGVPLTSGVSTSSpvepnDGTYSVTSSLTVPPSDWDEGAT 77

                         90
                 ....*....|....*...
gi 109032960 244 ITCVVKHPALEKDIRYSF 261
Cdd:cd00098   78 YTCVVTHESLKSPLSKTW 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 109032960 287 VNLKCNADANPPPfKSVWSR------LDGQWPDGLLASDNTLHFvHPLTFNYSGVYICKVTNSLG 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 109032960 287 VNLKCNADANPPPfKSVWSRLDGQWPDGL--LASDNTLHFVHpLTFNYSGVYICKVTNSLGQ 346
Cdd:cd05725   15 AEFQCEVGGDPVP-TVRWRKEDGELPKGRyeILDDHSLKIRK-VTAGDMGSYTCVAENMVGK 74

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960  66 VTAVWGKNVSLKCLIEVNETiTQISWEKihgKSSQTVavhhpqYGFSVQGEYQGRVLFKNYSLNDATITLHNIGFSDSGK 145
Cdd:cd05882    7 ETVAVGGTVTLKCGVKEHDN-SSLQWSN---TAQQTL------YFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGE 76

                         90
                 ....*....|....*....
gi 109032960 146 YICKAVTFPLGNAQSSTTV 164
Cdd:cd05882   77 YTCSIFTMPVRTAKATVTV 95

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 109032960  287 VNLKCNADANPPPfKSVWSRlDGQwpdgLLASDNTLHF----------VHPLTFNYSGVYICKVTNSLGQRS 348
Cdd:pfam07679  18 ARFTCTVTGTPDP-EVSWFK-DGQ----PLRSSDRFKVtyeggtytltISNVQPDDSGKYTCVATNSAGEAE 83

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960    73 NVSLKCLIEVNE-TITQISW-EKIHGKSSQTVAVHHPQYGFSVQGEYQGRVLF-KNYSLNDATITLHNIGFSDSGKYICK 149
Cdd:smart00406   1 SVTLSCKFSGSTfSSYYVSWvRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTIsKDTSKNDVSLTISNLRVEDTGTYYCA 80

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960  71 GKNVSLKCLIEVNETITQISWekIHGKSSQtvavhHPQY-------GFSVQGEYQGRVLFKNYSLNDATITLHNIGFSDS 143
Cdd:cd00099   13 GESVTLSCEVSSSFSSTYIYW--YRQKPGQ-----GPEFliylsssKGKTKGGVPGRFSGSRDGTSSFSLTISNLQPEDS 85

                         90       100
                 ....*....|....*....|....*.
gi 109032960 144 GKYICKAVTFPLGNAQ---SSTTVTV 166
Cdd:cd00099   86 GTYYCAVSESGGTDKLtfgSGTRLTV 111

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960  58 GPiivEPHVTAVWGKNVSLKCLI--EVNETITQISWekIHGKSSQtvAVHHPQYG---FSVQ-GEYQGRVLFKNYSLNDA 131
Cdd:cd05713    5 GP---TEPILALVGEDAELPCHLspKMSAEHMEVRW--FRSQFSP--VVHLYRDGqdqEEEQmPEYRGRTELLKDAIAEG 77

                         90
                 ....*....|....*....
gi 109032960 132 TITL--HNIGFSDSGKYIC 148
Cdd:cd05713   78 SVALriHNVRPSDEGQYTC 96

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109032960 167 LVEPTVSLIKGPDSLIDGGNEtVAAICIAATGKPVAHIDWEGDLGEM--ESTTTSFPNETATIISQYKLFPTRFARGRRI 244
Cdd:cd05883    1 LVPPRNLVIDIQKDTAVEGEE-IELNCTAMASKPAATIRWFKGNKELtgKSEVEEWYSRMFTVTSQLMLKVTKEDDGVPV 79

                         90
                 ....*....|...
gi 109032960 245 TCVVKHPALeKDI 257
Cdd:cd05883   80 ICLVDHPAV-KDL 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 109032960 128 LNDATITLHNIGFSDSGKYICKAVTFpLGNAQSSTTVTV 166
Cdd:cd04969   52 LPDGSLKIKNVTKSDEGKYTCFAVNF-FGKANSTGSLSV 89