Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  28 FTITGLERPVLAPLGGILELSCQLSPPQNAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVT 107
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 156523060 108 LRVFKVTVDDDGSYHCVFKDGIFYEEHITEVKVT 141
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 156523060  28 FTITGLERPVLAPLGGILELSCQLSPPQNAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVT 107
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 156523060 108 LRVFKVTVDDDGSYHCVFKDGIFYEEHITEVKVT 141
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

Immunoglobulin constant (IgC)-like domain of antigen receptor Cluster of Differentiation (CD) 80; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin constant (IgC)-like domain of the antigen receptor Cluster of Differentiation (CD) 80. CD80 (also known as glycoprotein B7-1) and CD86 (also known as glycoprotein B7-2) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules, and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig 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, and the IgC domain is involved in oligomerization and molecular interactions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060 130 FYEEHITEVKvtATSSDIKIIMhppnikgvmleCHSRGWFPQPHMEWRDsNGQVIPATSKSQSQD-ENKL--------FN 200
Cdd:cd16083    1 FPVPSITEFG--NPSPNIKRII-----------CSTSGGFPEPRLSWLE-NGEELNAINTTVSQDpETELytvsseldFN 66

                         90       100
                 ....*....|....*....|
gi 156523060 201 MTMNlfadvglHQIVtCYIQ 220
Cdd:cd16083   67 VTYN-------HSIV-CLIK 78

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 156523060  159 VMLECHSRGWFPQPHMEWRDSNGQVIPATSKSQSQDENKLFNMTMNLfaDVGLH-----QIVTCYIQN 221
Cdd:pfam08205  17 VVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSEL--KLVPSrsdhgQSLTCQVSY 82

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 156523060  28 FTITGLERPVLAPLGGILELSCQLSPPQNAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVT 107
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 156523060 108 LRVFKVTVDDDGSYHCVFKDGIFYEEHITEVKVT 141
Cdd:cd05713   81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

Immunoglobulin Variable (IgV) domain of B7-H3, a member of the B7 family of immune checkpoint molecules; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H3 also known as CD276), a member of the B7 family of immune checkpoint molecules. B7-H3 is an important immune checkpoint member of the B7 family and shares homology with other B7 ligands such as programmed death ligand 1 (PD-L1). The B7 family molecules interact with CD28 on T-cells to provide co-stimulatory signals that regulate T-cell activation and T-helper cell differentiation. Although B7-H3 has been shown to have both co-stimulatory and co-inhibitory effects on T-cell responses, the most current studies describe B7-H3 as a T cell inhibitor that promotes tumor aggressiveness and proliferation. Moreover, B7-H3 is highly overexpressed on a wide range of human solid cancers and promotes tumor growth, metastasis, and drug resistance. Thus, B7-H3 expression in tumors often correlates with both negative prognosis and poor clinical outcome in cancer patients. B7-H3 protein contains a predicted signal peptide, V- and C-like Ig domains (IgV and IgC), a transmembrane region, and an intracellular tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  34 ERPVLAPLGGILELSCQLSPPQ--NAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVTLRVF 111
Cdd:cd20934    4 EDPVVALVGTDATLRCSFSPEPgfSLAQLSVFWQLTDTKQLVHSFTESQDQGRDQGSAYANRTALFPDLLAQGNASLRLQ 83

                         90
                 ....*....|..
gi 156523060 112 KVTVDDDGSYHC 123
Cdd:cd20934   84 RVRVADEGSYTC 95

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 156523060  47 LSCQLSPPQNAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVTLRVFKVTVDDDGSYHCV 124
Cdd:cd20984   17 LSCTFTPDIKLSDIVIQWLKEGDSGLVHEFKEGKDELSRQSPMFRGRTSLFADQVHVGNASLRLKNVQLTDAGTYLCI 94

Immunoglobulin variable (IgV)-like domain in complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the immunoglobulin variable (IgV) region of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also known as Z39Ig and V-set and Ig domain-containing 4 (VSIG4) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. Like all members of this family, the CRIg domain contains two beta-sheets: one composed of strands A', G, F, C, C' and C", and the other of strands B, E and D. The complement system is an important part of the innate immune system and is required for removal of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convertases. CRIg, a complement receptor expressed on macrophages, binds to C3b and iC3b mediating phagocytosis of the particles. It is also a potent inhibitor of the alternative pathway convertases and a negative regulator of T cell activation. 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, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  33 LERP--VLAPLGGILELSCQLSPPQNAQQMEIRWFRNRYTEPVYLYRngKDLHGETI--SKYVERTELLKHdiGKGKVTL 108
Cdd:cd16089    3 LEGPesITGPWKGSVNLPCTYVPEEGYTQVLVKWLVQRDSDPVTIFL--RDSSGDHIqqAKYRGRLEVSKD--TPGDVSL 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 156523060 109 RVFKVTVDDDGSYHC--VFKD---GIFYEEHITEVKV 140
Cdd:cd16089   79 QLDTLEMDDRGHYTCqvTWQTpdgNLIVREKTTELRV 115

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  47 LSCQLSPpqnAQQMEIRWFRNRYTEPVYLYRNGKDLHGETISKYVERTELLKHDIGKGKVTLRVFKVTVDDDGSYHCVFK 126
Cdd:cd16091   17 LPCSFTP---GSEVVIHWYKQDSDIKVHSYYYGKDQLESQDQRYRNRTSLFKDQISNGNASLLLRRVQLQDEGRYKCYTS 93

                         90
                 ....*....|....
gi 156523060 127 DGIFYEEHITEVKV 140
Cdd:cd16091   94 TIIGNQESFVNLKV 107

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 156523060  159 VMLECHSRGWFPQPHMEWRDSNGQVIPATSKSQSQDENKLFNMTMNLfaDVGLH-----QIVTCYIQN 221
Cdd:pfam08205  17 VVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSEL--KLVPSrsdhgQSLTCQVSY 82

Immunoglobulin Variable (IgV) domain of T cell Immunoglobulin Domain and Mucin Domain 3 (Tim-3), and similar domains; The members here are composed of the immunoglobulin variable (IgV) domain of T cell immunoglobulin domain and mucin domain 3 (Tim-3; also known as Hepatitis A virus cellular receptor 2 (HAVcr-2) and Cluster of Differentiation 366 (CD366)) and similar proteins. TIM-3 is a checkpoint inhibitor in immune responses to tumors, as well as involved in chronic viral infections. Thus, Tim-3 has emerged as one of most promising immune checkpoint targets for cancer immunotherapy. Tim-3 is highly expressed on Th1 lymphocytes and CD11b(+) macrophages and is upregulated on activated T and myeloid cells. TIM-3 regulates macrophage, activation and inhibits Th1 mediated immune responses to promote immunological tolerance. There are three TIM family members in humans (TIM-1, TIM-3, and TIM-4) and eight members in mice (TIM-1 to TIM-8). The IgV domain of human TIM-3 has been shown to bind ligands such as carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), high mobility group protein B1 (HMGB1)and galectin-9 (GAL9). The binding of GAL9 to TIM-3 can negatively regulate Th1 immune response, enhance immune tolerance and inhibit anti#tumor immunity. Dysregulation of the TIM-3/GAL9 pathway is implicated in numerous chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  47 LSCQLSPPQNAQQMEIRWFRNR----YTEPVYLYRNGKDLHGETISKYverteLLKHDIGKGKVTLRVFKVTVDDDGSYH 122
Cdd:cd20982   13 LPCSYTTAAPGNLVPVCWGKGAcpvsYCGNVLLRTDERDVTYQKSSRY-----QLKGDFSKGDVSLTIENVTLADSGIYC 87

                         90       100
                 ....*....|....*....|
gi 156523060 123 CVFK-DGIFY-EEHITEVKV 140
Cdd:cd20982   88 CRIQiPGIMNdEKFNLKLVI 107

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156523060  45 LELSCQLSPPQNAQqmeIRWfrnrytepvylYRNGKDLHGETISKYVERTellkhdigkGKVTLRVFKVTVDDDGSYHCV 124
Cdd:cd00096    1 VTLTCSASGNPPPT---ITW-----------YKNGKPLPPSSRDSRRSEL---------GNGTLTISNVTLEDSGTYTCV 57