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 2024339461 176 PVVSLTKGPNPLIDGANQTIAAICTAATGKPAAEIDWEGGLGEMESSSTLFPNETVTVISQYTIIPTRFARGRRITCIVR 255
Cdd:cd07704     1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                          90
                  ....*....|....*.
gi 2024339461 256 HPALEKEIRFSHVLDI 271
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 2024339461 176 PVVSLTKGPNPLIDGANQTIAAICTAATGKPAAEIDWEGGLGEMESSSTLFPNETVTVISQYTIIPTRFARGRRITCIVR 255
Cdd:cd07704     1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                          90
                  ....*....|....*.
gi 2024339461 256 HPALEKEIRFSHVLDI 271
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 2024339461 275 PEVSVTGYDGNWFIGRENVQLRCNADANPLPMEFMWTRLDGQWPEGLLSVNNTLqFSSPLTYNYTGTYICKVTNSLGQRS 354
Cdd:cd20930     1 PEVSISGYDDNWYLGRNEATLTCDVRSNPEPTGYDWSTTSGPFPTSAVAQGPQL-LIHSVDRLVNTTFICTVTNAVGTGR 79

                  ....*..
gi 2024339461 355 DQKTIYI 361
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 2024339461   70 PHVTAVWGKKVALKCIIDVNETItQVSWEKIHGKTsetiavhhpeygISIQEKYQGKVSFKNYSLTdatiiLKNVSFSDA 149
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPP-EVTWYKQGGKL------------LAESGRFSVSRSGSTSTLT-----ISNVTPEDS 63

                           90       100
                   ....*....|....*....|...
gi 2024339461  150 GEYICkAVTFPLGNSQSSITVTV 172
Cdd:smart00410  64 GTYTC-AATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024339461 291 ENVQLRCNADANPLPmEFMWTRLDGQWPEG------LLSVNNTLQFSSpLTYNYTGTYICKVTN 348
Cdd:pfam13927  17 ETVTLTCEATGSPPP-TITWYKNGEPISSGstrsrsLSGSNSTLTISN-VTRSDAGTYTCVASN 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 2024339461 176 PVVSLTKGPNPLIDGANQTIAAICTAATGKPAAEIDWEGGLGEMESSSTLFPNETVTVISQYTIIPTRFARGRRITCIVR 255
Cdd:cd07704     1 PLVSLNPGPALLIDGGNETLAASCTAETGKPAASVTWETDLGGMESSRTFEHNRTATVTSEYHLVPTRFANGRPLTCVVS 80

                          90
                  ....*....|....*.
gi 2024339461 256 HPALEKEIRFSHVLDI 271
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 2024339461 176 PVVSLTKGPNPLIdGANQTIAAICTAATGKPAAEIDWEGGLGEMESSSTLFP-NETVTVISQYTIIPTRFARGRRITCIV 254
Cdd:cd05719     1 PTNSLEGGPALLI-GGEPTLVATCISANGKPPASVTWETDLKGEASTTQVRGsNGTVTVTSRYRLVPSREADGQPLTCVV 79

                          90
                  ....*....|....*..
gi 2024339461 255 RHPALEKEIRFSHVLDI 271
Cdd:cd05719    80 EHPSLEKDQRISVTLNV 96

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 2024339461  70 PHVTAVWGKKVALKCIIDVNETITQVSWEKIHGKtSETIAVHHPEYGISIQEKYQGKVSFKNYSLT--DATIILKNVSFS 147
Cdd:cd05889     7 WDTSVPLSENMSLECVYPSTGILTQVEWTKIGGQ-KDNIAVYHPTHGMHIRKPYAGRVYFLNSTMAsnNMSLSFRNASED 85

                          90       100
                  ....*....|....*....|...
gi 2024339461 148 DAGEYICKAVTFPLGNSQSSITV 170
Cdd:cd05889    86 DVGYYSCSLYTYPQGSWEKVIQV 108

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 2024339461  72 VTAVWGKKVALKCI--IDVNETITQVSWEKIH-GKTSETIAVHHPEYGISIQEKYQGKVSFK-NYSLTDATIILKNVSFS 147
Cdd:cd05888     3 VTVVLGQDAKLPCFyrGDSGEQVGQVAWARVDaGEGAQEIALLHSKYGLHVFPAYEGRVEQPpPPRPADGSVLLRNAVQA 82

                          90       100
                  ....*....|....*....|....*.
gi 2024339461 148 DAGEYICKAVTFPLGNSQSSITVTVL 173
Cdd:cd05888    83 DEGEYECRVSTFPAGNFQAELRLRVL 108

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461 163 NSQSSITVTVLVEPVVsltkgpnplidganqtiAAICTAATGKPAAEIDWEGGLGEM--ESSSTLFPNETVTVISQYTII 240
Cdd:cd07703     3 NSAEAQEVQAGGIPVP-----------------VARCVSANGRPPARISWSSTLNGNanTTQVPGPDSGTVTVTSEYSLV 65

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2024339461 241 PTRFARGRRITCIVRHPALEKEIRFSHVLDIQ 272
Cdd:cd07703    66 PTPEANGKEVTCKVEHETLEEPQLLPVTLSVR 97

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 2024339461  68 VDPHVTAVWGKKVALKCIIDVNE---TITQVSWEKiHGkTSETIAVHHPEYGISIQEKyqGKVSF----KNYSLTDATII 140
Cdd:cd20989     5 VPPEVRGFLGGSVTLPCHLLPPNmvtHVSQVTWQR-HD-EHGSVAVFHPKQGPSFPES--ERLSFvaarLGAELRNASLA 80

                          90       100
                  ....*....|....*....|..
gi 2024339461 141 LKNVSFSDAGEYICKAVTFPLG 162
Cdd:cd20989    81 MFGLRVEDEGNYTCEFATFPQG 102

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461  72 VTAVWGKKVALKCII--DVNETITQVSWEKIH--GKTSETIAVHHPEYGisiQEKYQGKVSF-KNYSLTDATIILKNVSF 146
Cdd:pfam07686   6 VTVALGGSVTLPCTYssSMSEASTSVYWYRQPpgKGPTFLIAYYSNGSE---EGVKKGRFSGrGDPSNGDGSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*..
gi 2024339461 147 SDAGEYICKAVTFPLGNSQSSITVTVL 173
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGKGTRLTVL 109

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461 176 PVVSLTKGpnpliDGANQTiaaiCTAATGKPAAEIDW--EGGL--GEMESSSTLFPNETVTVISQYTIIPTRFARGRRIT 251
Cdd:cd05759     8 PVISLQAG-----VPYNLT----CRARGAKPAAEIIWfrDGEQleGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFT 78

                  ....*...
gi 2024339461 252 CIVRHPAL 259
Cdd:cd05759    79 CRARNEAI 86

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 2024339461  70 PHVTAVWGKKVALKCIIDVNETITQVSWEKIHGKTSETIAvhhpeYGISIQEKYQGKVSFknyslTDATIILKNVSFSDA 149
Cdd:cd20946     7 QVVTVVENQEVILSCKTPKKTSSPRVEWKKLQRDVTFVVF-----QNNKIQGDYKGRAEI-----LGTNITIKNVTRSDS 76

                          90       100
                  ....*....|....*....|....*
gi 2024339461 150 GEYICKAVTFPLGNSQSSITVTVLV 174
Cdd:cd20946    77 GKYRCEVSARSDGQNLGEVTVTLEV 101

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). 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. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2024339461 199 CTAATGKPAAEIDWEGGLGEMESSSTLF---PN-ETVTVISQYTIIPTRFARGRRITCIVRHPALE 260
Cdd:cd07705    26 CTSSGSKPAANIKWRKGDQELEGAPTSVqedGNgKTFTVSSSVEFQVTREDDGAEITCSVGHESLH 91

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 2024339461 293 VQLRCNADANPLPmEFMWTR------LDGQWPEGLLSVNNTLQFSsPLTYNYTGTYICKVTNSLG 351
Cdd:cd00096     1 VTLTCSASGNPPP-TITWYKngkplpPSSRDSRRSELGNGTLTIS-NVTLEDSGTYTCVASNSAG 63

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461  72 VTAVWGKKVALKCIIDVNETiTQVSWEKIHGktsetiavhhpeygisiqEKYQGKVSFKNYSltdATIILKNVSFSDAGE 151
Cdd:cd05731     5 TMVLRGGVLLLECIAEGLPT-PDIRWIKLGG------------------ELPKGRTKFENFN---KTLKIENVSEADSGE 62

                          90       100
                  ....*....|....*....|.
gi 2024339461 152 YICKAVTfPLGNSQSSITVTV 172
Cdd:cd05731    63 YQCTASN-TMGSARHTISVTV 82

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024339461 291 ENVQLRCNADANPLPmEFMWTRLDGQWPEG------LLSVNNTLQFSSpLTYNYTGTYICKVTN 348
Cdd:pfam13927  17 ETVTLTCEATGSPPP-TITWYKNGEPISSGstrsrsLSGSNSTLTISN-VTRSDAGTYTCVASN 78

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461  70 PHVTAVWGKKVALKCIIDVNETIT---------QVSWEKIH---GKTSETIAVHHPEYGISIQEKYQGKVSFKNY--SLT 135
Cdd:cd05878     5 SPVRVLLGTSVTLPCYFIDPPHPVtpstaplapRIKWSKVSvdgKKEKEVVLLVATEGRVRVNSAYQGRVSLPNYpaIPS 84

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2024339461 136 DATIILKNVSFSDAGEYICKaVTFPLGNSQSSITVTV 172
Cdd:cd05878    85 DATLEVQSLRASDSGLYRCE-VMHGIEDSQDTVELVV 120

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024339461 275 PEVSVTGYDGnwfigrENVQLRCNADANPLPMEFMWTRLDGQWPEGLLSV-------NNTLQFSsPLTYNYTGTYICKVT 347
Cdd:pfam00047   2 APPTVTVLEG------DSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKhdngrttQSSLLIS-NVTKEDAGTYTCVVN 74

                  ....*
gi 2024339461 348 NSLGQ 352
Cdd:pfam00047  75 NPGGS 79

Immunoglobulin V-Type;

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024339461   91 TITQVSW-EKIHGKTSETIAVHHPEYGISIQEKYQGKVSF-KNYSLTDATIILKNVSFSDAGEYICK 155
Cdd:smart00406  14 SSYYVSWvRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTIsKDTSKNDVSLTISNLRVEDTGTYYCA 80

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.

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                  ....*....|....*....|....*....|....*..
gi 2024339461 230 TVTVISQYTIIPTRFARGRRITCIVRHPALEKEIRFS 266
Cdd:cd05771    64 TYSISSYLTLEPGTENRGATYTCRVTHVSLEEPLSVS 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2024339461 199 CTAATGKPAAEIDWEGGLGEMESSSTLFPNETVTVISQYTIIPTRFARGRRITCIVRHPALEKEIRFS 266
Cdd:pfam00047  18 CSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTS 85

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024339461 291 ENVQLRCNADANPLPmEFMWTRLDGQWPEGLLSV--NNTLQFSSpLTYNYTGTYICKVTNSLGQ 352
Cdd:cd05725    13 DSAEFQCEVGGDPVP-TVRWRKEDGELPKGRYEIldDHSLKIRK-VTAGDMGSYTCVAENMVGK 74

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. In CSPGs, the 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 HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. 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 2024339461  94 QVSWEKIhGKTSETIAVHHPEYGISIQEKYQGKVSFKNYSL--TDATIILKNVSFSDAGEYICKaVTFPLGNSQSSITVT 171
Cdd:cd05900    40 RIKWSFI-SKEKESVLLVATEGKVRVNTEYLDRVSLPNYPAipSDATLEITELRSNDSGTYRCE-VMHGIEDNYDTVEVQ 117

                  .
gi 2024339461 172 V 172
Cdd:cd05900   118 V 118

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 2024339461 121 EKYQGKVSF-KNYSLTDATIILKNVSFSDAGEYICKAVTFPlGNSQSSITVT 171
Cdd:cd20960    64 PALKGRVAFtSNDLSGDASLNISNLKLSDTGTYQCKVKKAP-GYAWSKITLI 114

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 2024339461 291 ENVQLRCNADANPlPMEFMWTrldgqWPEGLLSVNNTLqFSSPLTYNYTGTYICKVTNSLG--QRSDQKTI 359
Cdd:cd20948    11 ENLNLSCHAASNP-PAQYSWT-----INGTFQTSSQEL-FLPAITENNEGTYTCSAHNSLTgkNISLVLSV 74