Immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA); The members here are composed of the immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA; also known as B7-H5, PD-1H, Gi24, Dies1, SISP1 and DD1alpha). VISTA is an immune checkpoint protein involved in the regulation of T cell activity and inhibits the T cell response against cancer. VISTA is a type I transmembrane protein with a single IgV domain with sequence homology to the IgV domains of the members of B7 family. VISTA is the only B7 family member that lacks an IgC domain. VISTA is primarily expressed in white blood cells and its transcription is partially controlled by p53. Similar to PD-1/PD-L1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Unlike the B7 family members, VISTA contains 10 beta-strands, instead of the nine that typically comprises of an IgV fold. Moreover, human VISTA contains the 21-residue extended loop between stands C and C', which does not align with any B7 family structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 227330580  34 KVTTPYSLYVCPEGQNATLTCRILGPVSKGHDVTIYKTWYLSSRGEVQMCKEHRPIRNFTLQHLQHHGSHLKANASHDQP 113
Cdd:cd20980    1 KVATPYSLYVCPEGQNVTLTCRLLGPVDKGHDVTFYKTWYRSSRGEVQTCSERRPIRNLTFQDLHLHHGGQAANTSHDLA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 227330580 114 QKHGLELASDHHGNFSITLRNVTPRDSGLYCCLVIELKNHHPEQRFYGSMELQVQAGKGSGSTCMAS 180
Cdd:cd20980   81 QRHGLESASDHHGNFSITMRNLTLLDSGLYCCLVVEIRHHHSEQRLYGAMELQVQTGKDAPSTCVAY 147

Immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA); The members here are composed of the immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA; also known as B7-H5, PD-1H, Gi24, Dies1, SISP1 and DD1alpha). VISTA is an immune checkpoint protein involved in the regulation of T cell activity and inhibits the T cell response against cancer. VISTA is a type I transmembrane protein with a single IgV domain with sequence homology to the IgV domains of the members of B7 family. VISTA is the only B7 family member that lacks an IgC domain. VISTA is primarily expressed in white blood cells and its transcription is partially controlled by p53. Similar to PD-1/PD-L1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Unlike the B7 family members, VISTA contains 10 beta-strands, instead of the nine that typically comprises of an IgV fold. Moreover, human VISTA contains the 21-residue extended loop between stands C and C', which does not align with any B7 family structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 227330580  34 KVTTPYSLYVCPEGQNATLTCRILGPVSKGHDVTIYKTWYLSSRGEVQMCKEHRPIRNFTLQHLQHHGSHLKANASHDQP 113
Cdd:cd20980    1 KVATPYSLYVCPEGQNVTLTCRLLGPVDKGHDVTFYKTWYRSSRGEVQTCSERRPIRNLTFQDLHLHHGGQAANTSHDLA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 227330580 114 QKHGLELASDHHGNFSITLRNVTPRDSGLYCCLVIELKNHHPEQRFYGSMELQVQAGKGSGSTCMAS 180
Cdd:cd20980   81 QRHGLESASDHHGNFSITMRNLTLLDSGLYCCLVVEIRHHHSEQRLYGAMELQVQTGKDAPSTCVAY 147

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 227330580    38 PYSLYVcPEGQNATLTCRILGpvskghDVTIYKTWYLssrgevqmckehrpirnftlQHLQHHGSHLKANASHDqpqkhg 117
Cdd:smart00410   1 PPSVTV-KEGESVTLSCEASG------SPPPEVTWYK--------------------QGGKLLAESGRFSVSRS------ 47

                           90       100       110
                   ....*....|....*....|....*....|
gi 227330580   118 lelasdhHGNFSITLRNVTPRDSGLYCCLV 147
Cdd:smart00410  48 -------GSTSTLTISNVTPEDSGTYTCAA 70

Immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA); The members here are composed of the immunoglobulin variable (IgV) domain of V-domain immunoglobulin suppressor of T cell activation (VISTA; also known as B7-H5, PD-1H, Gi24, Dies1, SISP1 and DD1alpha). VISTA is an immune checkpoint protein involved in the regulation of T cell activity and inhibits the T cell response against cancer. VISTA is a type I transmembrane protein with a single IgV domain with sequence homology to the IgV domains of the members of B7 family. VISTA is the only B7 family member that lacks an IgC domain. VISTA is primarily expressed in white blood cells and its transcription is partially controlled by p53. Similar to PD-1/PD-L1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Unlike the B7 family members, VISTA contains 10 beta-strands, instead of the nine that typically comprises of an IgV fold. Moreover, human VISTA contains the 21-residue extended loop between stands C and C', which does not align with any B7 family structure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 227330580  34 KVTTPYSLYVCPEGQNATLTCRILGPVSKGHDVTIYKTWYLSSRGEVQMCKEHRPIRNFTLQHLQHHGSHLKANASHDQP 113
Cdd:cd20980    1 KVATPYSLYVCPEGQNVTLTCRLLGPVDKGHDVTFYKTWYRSSRGEVQTCSERRPIRNLTFQDLHLHHGGQAANTSHDLA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 227330580 114 QKHGLELASDHHGNFSITLRNVTPRDSGLYCCLVIELKNHHPEQRFYGSMELQVQAGKGSGSTCMAS 180
Cdd:cd20980   81 QRHGLESASDHHGNFSITMRNLTLLDSGLYCCLVVEIRHHHSEQRLYGAMELQVQTGKDAPSTCVAY 147

Immunoglobulin Variable (IgV) domain of Programmed death ligand 1 (PD-L1); The members here are composed of the immunoglobulin variable (IgV) domain of Programmed death ligand 1 (PD-L1; also known as Cluster of Differentiation 274 (CD274)). PD-L1 is a cell-surface ligand that competes with PD-L2 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. Like PD-L2, PD-L1 interacts with PD-1 and suppresses T cell proliferation and cytokine production. The PD-1 receptor is expressed on the surface of activated T cells, while PD-L1 is expressed on cancer cells. When PD-1 and PD-L1 bind together, they form a molecular shield protecting tumor cells from being destroyed by the immune system. Thus, inhibiting the binding of PD-L1 to PD-1 with an antibody leads to killing of tumor cells by T cells. PD-1 inhibitors (such as Pembrolizumab, Nivolumab, and Cemiplimab) and PD-L1 inhibitors (such as Atezolizumab, Avelumab, and Durvalumab ) are an emerging class of immunotherapy that stimulate lymphocytes against tumor cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 227330580  35 VTTPYSLYVCPEGQNATLTCRIlgPVSKGHDVT---IYktWYLSSRGEVQMCKEHRPIRnftlqhLQHHGSHLKANASHD 111
Cdd:cd20947    1 VTVPKDLYVVEYGSNMTIECKF--PVEKQLDLAaliVY--WEMEDKNIIQFVHGEEDLK------VQHSSYRQRARLLKD 70

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 227330580 112 QPQKhglelasdhhGNFSITLRNVTPRDSGLYCCLV 147
Cdd:cd20947   71 QLSL----------GNAALQITDVKLQDAGVYRCMI 96

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 227330580  46 EGQNATLTCRilgpVSKGHDVTIykTWyLSSRGEVQMCKEHRPIRNFTLQhLQHHGSHlkanashdqpqkhglelasdhh 125
Cdd:cd05717   10 EGETLTLKCQ----VSLRDDSSL--QW-LNPNGQTIYFNDKRALRDSRYQ-LLNHSAS---------------------- 59

                         90       100
                 ....*....|....*....|.
gi 227330580 126 gNFSITLRNVTPRDSGLYCCL 146
Cdd:cd05717   60 -ELSISVSNVTLSDEGVYTCL 79

Immunoglobulin Variable (IgV) domain of B7-H2 (B7 homolog 2); The members here are composed of the immunoglobulin variable (IgV) domain of B7-H2 (B7 homolog 2 also known as ICOSL (inducible T cell costimulator ligand) or CD275). B7-H2 is a ligand for the T-cell-specific cell surface receptor ICOS and acts as a costimulatory signal for T-cell proliferation and cytokine secretion. The interaction of ICOS with ICOSL (B7-H2) regulates T cell activation and expansion, is involved in T cell dependent B cell activation, and T-helper cell differentiation. It is a member of the B7 family of immune regulatory proteins and shares homology with other B7 ligands, such as B7-1, B7-2, B7-H1 (PD-L1), PD-L2, and B7-H3. The extracellular domains of B7 proteins contain two Ig-like domains and all members have short cytoplasmic domains. These ligands are typically expressed on antigen presenting cells (such as macrophages, B cells and dendritic cells) and have the ability to regulate T-cell proliferation and function. Tumor cells are also capable of expressing the B7 family members in order to evade immune surveillance.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 227330580 118 LELASDHHGNFSITLRNVTPRDSGLYCCLVielknhhpeqrFYGSMELQ 166
Cdd:cd20935   64 LSLDSMKQGDFSLRLFNVTPQDEQKFHCLV-----------FSQSLELQ 101

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
                 ....*....|....*....|....*.
gi 227330580 122 SDHHGNFSITLRNVTPRDSGLYCCLV 147
Cdd:cd00096   33 RSELGNGTLTISNVTLEDSGTYTCVA 58