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 74757248  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 74757248 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   362 KPSMTLEPNK-DLRPGDTVTITCSSyRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRvvlGANGTYSCLV 440
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTR---SDAGTYTCVA 76

                  ..
gi 74757248   441 RN 442
Cdd:pfam13927  77 SN 78

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 74757248  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 74757248 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   362 KPSMTLEPNK-DLRPGDTVTITCSSyRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRvvlGANGTYSCLV 440
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTR---SDAGTYTCVA 76

                  ..
gi 74757248   441 RN 442
Cdd:pfam13927  77 SN 78

Immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2); The members here are composed of the immunoglobulin Constant 1 (IgC1) domain of Programmed death ligand 2 (PD-L2; also known as B7-DC or CD273). PD-L2 is a cell-surface ligand that competes with PD-L1 for binding to the immunosuppressive receptor programmed death-1 (PD-1). PD-1 is a member of the CD28/B7 family that plays an important role in negatively regulating immune responses upon interaction with its two ligands, PD-L1 or PD-L2. PD-L2 has a higher affinity for PD-1 but is expressed at lower levels. PD-L2 interaction with PD-1 suppresses T cell proliferation, cytokine production and cytotoxic activity. PD-L2 is expressed on tumor cells, antigen-presenting cells or APCs (such as macrophages, B cells and dendritic cells), and a variety of other immune and nonimmune cells. Tumor expression of PD-L2 may contribute to tumor evasion of immune destruction by inactivating T cells. Thus, PD-L2 is a negative predictor for prognosis among solid cancer patients.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 74757248 375 PG-DTVTITCSSyRGYPEAEVFWQDgqgVPLTGNvtTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRN 442
Cdd:cd20986   8 PGtGEVQLTCQA-RGYPLAEVSWQN---VSVPAN--TSHTRTPEGLYQVTSVLRLKPQPGRNFSCMFWN 70

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74757248 161 VTITCSsYQGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLfdvhSILRVVLGANGTYSCLVRNPVLQQDAHS 233
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWYkNGKPLPPSSRDSRRSELGNGTL----TISNVTLEDSGTYTCVASNSAGGSASAS 69

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248    374 RPGDTVTITCsSYRGYPEAEVFW--QDGQGVPLTGNVTTSQMANEQGLFdvhsVLRVVLGANGTYSCLVRNPVlqQDAHG 451
Cdd:smart00410   7 KEGESVTLSC-EASGSPPPEVTWykQGGKLLAESGRFSVSRSGSTSTLT----ISNVTPEDSGTYTCAATNSS--GSASS 79

                   ....*
gi 74757248    452 SVTIT 456
Cdd:smart00410  80 GTTLT 84

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248     45 DATLCCSFSpepGFSLAQLNLIWQ-LTDTKQLVHsFAEGQDQGSAYA-----NRTALFPDLlAQGNASLRLQRVRVADEG 118
Cdd:smart00406   1 SVTLSCKFS---GSTFSSYYVSWVrQPPGKGLEW-LGYIGSNGSSYYqesykGRFTISKDT-SKNDVSLTISNLRVEDTG 75

                   ....*.
gi 74757248    119 SFTCFV 124
Cdd:smart00406  76 TYYCAV 81

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 74757248  32 QVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQ----DQGSAYANRTALFPDLLAQGNASL 107
Cdd:cd20934   1 RVPEDPVVALVGTDATLRCSFSPEPGFSLAQLSVFWQLTDTKQLVHSFTESQdqgrDQGSAYANRTALFPDLLAQGNASL 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 74757248 108 RLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPY 142
Cdd:cd20934  81 RLQRVRVADEGSYTCFVSVQDFGSAAVSLQVAAPF 115

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 74757248  34 PEDPVVALVGTDATLCCSFSPEpgFSLAQLNLIWQLTDTKQLVHSFAEGQDQGS----AYANRTALFPDLLAQGNASLRL 109
Cdd:cd05713   6 PTEPILALVGEDAELPCHLSPK--MSAEHMEVRWFRSQFSPVVHLYRDGQDQEEeqmpEYRGRTELLKDAIAEGSVALRI 83

                        90       100       110
                ....*....|....*....|....*....|.
gi 74757248 110 QRVRVADEGSFTCFVSIRDF-GSAAVSLQVA 139
Cdd:cd05713  84 HNVRPSDEGQYTCFFRSGSFyEEATLELKVA 114

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248 257 VALVGTDATLRCSFSPEPgfSLAQLNLIWQLTDTKQLVHSFTEGRD----QGSAYANRTALFPDLLAQGNASLRLQRVRV 332
Cdd:cd20984   8 AGNIGEDGILSCTFTPDI--KLSDIVIQWLKEGDSGLVHEFKEGKDelsrQSPMFRGRTSLFADQVHVGNASLRLKNVQL 85

                        90
                ....*....|.
gi 74757248 333 ADEGSFTCFVS 343
Cdd:cd20984  86 TDAGTYLCIIS 96

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 74757248  35 EDPVVALVGTDATLCCSFSPEPgfslaQLNLIWQLTDTKQLVHSFAEGQD----QGSAYANRTALFPDLLAQGNASLRLQ 110
Cdd:cd16091   4 EVIVVCLLSEDCILPCSFTPGS-----EVVIHWYKQDSDIKVHSYYYGKDqlesQDQRYRNRTSLFKDQISNGNASLLLR 78

                        90       100
                ....*....|....*....|....*....
gi 74757248 111 RVRVADEGSFTCFVS-IRDFGSAAVSLQV 138
Cdd:cd16091  79 RVQLQDEGRYKCYTStIIGNQESFVNLKV 107

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 74757248  31 VQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTK--QLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLR 108
Cdd:cd20947   1 VTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNiiQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQ 80

                        90
                ....*....|....*..
gi 74757248 109 LQRVRVADEGSFTCFVS 125
Cdd:cd20947  81 ITDVKLQDAGVYRCMIS 97

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248  38 VVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQG----SAYANRTALFPDLLAQGNASLRLQRVR 113
Cdd:cd20935   3 VRAMVGSDVELSCICPEGSRFDLNDLYVYWQISESETVVTYHLPQNSSLenvdSHYRNRALLSLDSMKQGDFSLRLFNVT 82

                        90       100       110
                ....*....|....*....|....*....|.
gi 74757248 114 VADEGSFTCFVSIRDFG-----SAAVSLQVA 139
Cdd:cd20935  83 PQDEQKFHCLVFSQSLElqkvlEVVVTLHVA 113

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   362 KPSMTLEPNK-DLRPGDTVTITCSSyRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRvvlGANGTYSCLV 440
Cdd:pfam13927   1 KPVITVSPSSvTVREGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTR---SDAGTYTCVA 76

                  ..
gi 74757248   441 RN 442
Cdd:pfam13927  77 SN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   366 TLEPNKDLRPGD--TVTITCSSYRGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVL--GANG-TYSCLV 440
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 74757248   441 RNPVLQQDA 449
Cdd:pfam08205  81 SYGALRGSI 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   148 TLEPNKDLRPGD--TVTITCSSYQGYPEAEVFWQdGQGVPLTGNVTTSQMANEQGLFDVHSILRVVL--GANG-TYSCLV 222
Cdd:pfam08205   2 TIEPPASLLEGEgpEVVATCSSAGGKPAPRITWY-LDGKPLEAAETSSEQDPESGLVTVTSELKLVPsrSDHGqSLTCQV 80

                  ....*....
gi 74757248   223 RNPVLQQDA 231
Cdd:pfam08205  81 SYGALRGSI 89

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 74757248   250 QVPEDPVVALvGTDATLRCSFSPEPgfSLAQLNLIWQLTDT----KQLVHSFTEGRDQGSaYANRTALFPDLlAQGNASL 325
Cdd:pfam07686   1 QTPREVTVAL-GGSVTLPCTYSSSM--SEASTSVYWYRQPPgkgpTFLIAYYSNGSEEGV-KKGRFSGRGDP-SNGDGSL 75

                          90
                  ....*....|....*
gi 74757248   326 RLQRVRVADEGSFTC 340
Cdd:pfam07686  76 TIQNLTLSDSGTYTC 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   369 PNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNvTTSQMANEQGLFDVHsVLRVVLGANGTYSCLVRNPVLQQD 448
Cdd:pfam00047   4 PTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESL-KVKHDNGRTTQSSLL-ISNVTKEDAGTYTCVVNNPGGSAT 81

                  .
gi 74757248   449 A 449
Cdd:pfam00047  82 L 82

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 86; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 86). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. The CTLA-4 and B7-2 monomers are both two-layer beta-sandwiches that display the chain topology characteristic of the immunoglobulin variable (V-type) domains present in antigen receptors. The front and back sheets of B7-2 are composed of AGFCC'C" and BED strands, respectively. Members of the IgV family 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248  38 VVALVGTDATLCCSFSPEPGFSLAQLNLIWQlTDTKQLVHSFAEGQDQ----GSAYANRTALfpdllAQGNASLRLQRVR 113
Cdd:cd16087   3 IQAYFNETAYLPCQFKNPQNISLSELVVFWQ-DQKKLVLYELYLGKEKldnvNSKYIGRTSF-----DQENWTLQLHNVQ 76

                        90
                ....*....|.
gi 74757248 114 VADEGSFTCFV 124
Cdd:cd16087  77 IKDQGTYQCFI 87

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 74757248 161 VTITCSsYQGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLfdvhSILRVVLGANGTYSCLVRNPVLQQDAHS 233
Cdd:cd00096   1 VTLTCS-ASGNPPPTITWYkNGKPLPPSSRDSRRSELGNGTL----TISNVTLEDSGTYTCVASNSAGGSASAS 69

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 74757248 247 VEVQVPEDpVVALVGTDATLRCSF-SPEPGFSLAQLNliWQLTDTKQLVHSFTEgrDQGSAYAN-------RTALFPDLL 318
Cdd:cd20989   1 VRVQVPPE-VRGFLGGSVTLPCHLlPPNMVTHVSQVT--WQRHDEHGSVAVFHP--KQGPSFPEserlsfvAARLGAELR 75

                        90       100
                ....*....|....*....|..
gi 74757248 319 aqgNASLRLQRVRVADEGSFTC 340
Cdd:cd20989  76 ---NASLAMFGLRVEDEGNYTC 94

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 74757248  31 VQVPEDpVVALVGTDATLCCSF-SPEPGFSLAQLNliWQLTDTKQLVHSFAegQDQGSAYAN-------RTALFPDLLaq 102
Cdd:cd20989   3 VQVPPE-VRGFLGGSVTLPCHLlPPNMVTHVSQVT--WQRHDEHGSVAVFH--PKQGPSFPEserlsfvAARLGAELR-- 75

                        90       100
                ....*....|....*....|
gi 74757248 103 gNASLRLQRVRVADEGSFTC 122
Cdd:cd20989  76 -NASLAMFGLRVEDEGNYTC 94

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   251 VPEDPVVALVGTDATLRCSFSPEPGFslaqLNLIWQLTDtKQLVHSFTEGRDQGSayanrtalfpdllaQGNASLRLQRV 330
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPG----PDVTWSKEG-GTLIESLKVKHDNGR--------------TTQSSLLISNV 61

                          90       100
                  ....*....|....*....|...
gi 74757248   331 RVADEGSFTCFVSIRDFGSAAVS 353
Cdd:pfam00047  62 TKEDAGTYTCVVNNPGGSATLST 84

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 74757248 369 PNKDLRPGDTVTITCSSYRGYPEaEVF--W-QDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGA--NG-TYSCLV 440
Cdd:cd05768   9 PEEELSLNETVTLTCLVKGFYPE-DIFvsWlQNGEPLPSADYKTTAPVPESDGSFFVYSKLNVSTADwnSGdVFSCVV 85

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 74757248 372 DLRPGDTVTITCSSYRGYPE-AEVFW-QDGQGVPlTGNVTTSQMANEQGLFDVHSVLRVVLG---ANGTYSCLVRNPVLQ 446
Cdd:cd00098  10 EEKGGGKVTLVCLVSGFYPKdITVTWlKNGVPLT-SGVSTSSPVEPNDGTYSVTSSLTVPPSdwdEGATYTCVVTHESLK 88

                .
gi 74757248 447 Q 447
Cdd:cd00098  89 S 89

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248     45 DATLCCSFSpepGFSLAQLNLIWQ-LTDTKQLVHsFAEGQDQGSAYA-----NRTALFPDLlAQGNASLRLQRVRVADEG 118
Cdd:smart00406   1 SVTLSCKFS---GSTFSSYYVSWVrQPPGKGLEW-LGYIGSNGSSYYqesykGRFTISKDT-SKNDVSLTISNLRVEDTG 75

                   ....*.
gi 74757248    119 SFTCFV 124
Cdd:smart00406  76 TYYCAV 81

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248 376 GDTVTITCSsYRGYPEAEVFWQ-DGQGVPLTGNvttsQMANEQGLFDVHSVLRVVlgANGTYSCLVRNPVlQQDAHGSVT 454
Cdd:cd20958  15 GQTLRLHCP-VAGYPISSITWEkDGRRLPLNHR----QRVFPNGTLVIENVQRSS--DEGEYTCTARNQQ-GQSASRSVF 86

                ..
gi 74757248 455 IT 456
Cdd:cd20958  87 VK 88

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248   145 PSMTLEP-NKDLRPGDTVTITCSSyQGYPEAEVFWQ-DGQGVPLTGNVTTSQMANEQGLFdvhsILRVVLGANGTYSCLV 222
Cdd:pfam07679   1 PKFTQKPkDVEVQEGESARFTCTV-TGTPDPEVSWFkDGQPLRSSDRFKVTYEGGTYTLT----ISNVQPDDSGKYTCVA 75

                          90
                  ....*....|....*
gi 74757248   223 RNPVLQQDAHSSVTI 237
Cdd:pfam07679  76 TNSAGEAEASAELTV 90

Class II major histocompatibility complex (MHC) beta chain immunoglobulin domain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class II beta chain. MHC class II molecules play a key role in the initiation of the antigen-specific immune reponse. These molecules have been shown to be expressed constitutively on the cell surface of professional antigen-presenting cells (APCs), including B-lymphocytes, monocytes, and macrophages in both humans and mice. The expression of these molecules has been shown to be induced in nonprofessional APCs such as keratinocyctes and they are also expressed on the surface of activated human T cells and on T cells from other species. The MHC II molecules present antigenic peptides to CD4(+) T-lymphocytes. These peptides derive mostly from proteolytic processing via the endocytic pathway of antigens internalized by the APC. These peptides bind to the MHC class II molecules in the endosome before they are transported to the cell surface. MHC class II molecules are heterodimers, comprised of two similarly-sized membrane-spanning chains, alpha and beta. Each chain has two globular domains (N- and C-terminal) and a membrane-anchoring transmembrane segment. The two chains form a compact four-domain structure. The peptide-binding site is a cleft in the structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 74757248 144 KPSMTLEPNKDLRPGDTVTITCSSYQGYP-EAEVFW-QDGQGVPlTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCL 221
Cdd:cd05766   3 QPSVKVSPTKTGPLEHPNLLVCSVTGFYPaEIEVKWfRNGQEET-AGVVSTELIPNGDWTFQILVMLETTPRRGDVYTCQ 81

                ....*...
gi 74757248 222 VRNPVLQQ 229
Cdd:cd05766  82 VEHSSLQS 89

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 74757248 145 PSMTLEPNKDLRPGD--TVTITCSSYQGYPEAEVFWqDGQgvpLTGNVTTSQMANEQGLFDVHSILRVVLG--ANG-TYS 219
Cdd:cd05719   1 PTNSLEGGPALLIGGepTLVATCISANGKPPASVTW-ETD---LKGEASTTQVRGSNGTVTVTSRYRLVPSreADGqPLT 76

                        90
                ....*....|....*....
gi 74757248 220 CLVRNPVLQQDAHSSVTIT 238
Cdd:cd05719  77 CVVEHPSLEKDQRISVTLN 95