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 829986063 136 FSQPEIMEIsnGTENSGIINVTCSSQQGYPEPIKMFFviktENSSDEYMANMMIYQDNVTELYSVSASLSFPV 208
Cdd:cd16083    1 FPVPSITEF--GNPSPNIKRIICSTSGGFPEPRLSWL----ENGEELNAINTTVSQDPETELYTVSSELDFNV 67

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 829986063    38 LPCRFKNPQNTsldELVVFWQNQ--DKVLYELYTGSENPHNV-HPMYKGRTSF----DLGSWTLKLHNIEIKDEGTYYC 109
Cdd:smart00406   4 LSCKFSGSTFS---SYYVSWVRQppGKGLEWLGYIGSNGSSYyQESYKGRFTIskdtSKNDVSLTISNLRVEDTGTYYC 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 829986063 136 FSQPEIMEIsnGTENSGIINVTCSSQQGYPEPIKMFFviktENSSDEYMANMMIYQDNVTELYSVSASLSFPV 208
Cdd:cd16083    1 FPVPSITEF--GNPSPNIKRIICSTSGGFPEPRLSWL----ENGEELNAINTTVSQDPETELYTVSSELDFNV 67

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 829986063  25 AETSQAYFGDTGLLPCRFKnpQNTSLDELVVFWQNQD--KVLYELYTGSENPHNVHPMYKGRTSFDL-----GSWTLKLH 97
Cdd:cd20984    4 AKHLAGNIGEDGILSCTFT--PDIKLSDIVIQWLKEGdsGLVHEFKEGKDELSRQSPMFRGRTSLFAdqvhvGNASLRLK 81

                         90
                 ....*....|....
gi 829986063  98 NIEIKDEGTYYCYV 111
Cdd:cd20984   82 NVQLTDAGTYLCII 95

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 829986063  30 AYFGDTGLLPCRFKNPQNTSLDELVVFWQ--NQDKVLYELYTGSENPHNVHPMYKGRTSF--DL---GSWTLKLHNIEIK 102
Cdd:cd20934    9 ALVGTDATLRCSFSPEPGFSLAQLSVFWQltDTKQLVHSFTESQDQGRDQGSAYANRTALfpDLlaqGNASLRLQRVRVA 88

                 ....*....
gi 829986063 103 DEGTYYCYV 111
Cdd:cd20934   89 DEGSYTCFV 97

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 829986063  32 FGDTGLLPCRFknpqnTSLDELVVFW--QNQDKVLYELYTGSENPHNVHPMYKGRTS-----FDLGSWTLKLHNIEIKDE 104
Cdd:cd16091   11 LSEDCILPCSF-----TPGSEVVIHWykQDSDIKVHSYYYGKDQLESQDQRYRNRTSlfkdqISNGNASLLLRRVQLQDE 85

                         90
                 ....*....|....
gi 829986063 105 GTYYCYVHHKQRNI 118
Cdd:cd16091   86 GRYKCYTSTIIGNQ 99

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 80; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 80). 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 cluster of differentiation 152/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 829986063  37 LLPCRFknpqNTSLDELV---VFWQNQDKVLYELYTGSENphnVHPMYKGRTSFDL-GSWTLKLHNIEIKDEGTYYCYVH 112
Cdd:cd16086   13 LLSCDY----NVSVDELAqvrIYWQKDDKMVLTIISGDVK---VWPEYKNRTLFDItNNLSIVILALRLSDRGTYTCVVQ 85

                 ....
gi 829986063 113 HKQR 116
Cdd:cd16086   86 KKER 89

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 829986063  33 GDTGLLPCRFKNPQNTSldelVVFW--QNQDKVLYELYTGSENPHNVHPMYKGR--TSFDLG-SWTLKLHNIEIKDEGTY 107
Cdd:cd00099   13 GESVTLSCEVSSSFSST----YIYWyrQKPGQGPEFLIYLSSSKGKTKGGVPGRfsGSRDGTsSFSLTISNLQPEDSGTY 88

                 ..
gi 829986063 108 YC 109
Cdd:cd00099   89 YC 90

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 829986063  33 GDTGLLPCRFKNPqntSLDELVVFWQNQ------DKVLYELYTGSENP--HNVHPMYKGRTSFDLGSWTLKLHNIEIKDE 104
Cdd:cd04982   13 SKSVTISCKVSGI---DFSTTYIHWYRQkpgqalERLLYVSSTSAVRKdsGKTKNKFEARKDVGKSTSTLTITNLEKEDS 89

                 ....*
gi 829986063 105 GTYYC 109
Cdd:cd04982   90 ATYYC 94

First immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 829986063  33 GDTGLLPCrfKNPQNTSLDelvVFWQN--QDKVL-YELYTGSENPHNVHPMYKGRTS-FDLGSWTLKLHNIEIKDEGTYY 108
Cdd:cd07690    9 GDTAELPC--TASQKKSIQ---FHWKNsnQIKILgNQGSFLTKGPSKLNDRADSRRNlWDQGSFPLIIKNLKIEDSDTYI 83

                         90
                 ....*....|
gi 829986063 109 CYVHHKQRNI 118
Cdd:cd07690   84 CEVEDKKEEV 93

First immunoglobulin variable (IgV) domain of nectin-1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-1 (also known as poliovirus receptor related protein 1 (PVRL1) or cluster of differentiation (CD) 111). Nectin-1 belongs to the nectin family comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. In addition nectins heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls), nectin-1 for example, has been shown to trans-interact with Necl-1. Nectins also interact with various other proteins, including the actin filament (F-actin)-binding protein, afadin. Mutation in the human nectin-1 gene is associated with cleft lip/palate ectodermal dysplasia syndrome (CLPED1). Nectin-1 is a major receptor for herpes simplex virus through interaction with the viral envelope glycoprotein D.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 829986063  26 ETSQAYFGDTGLLPCRFKNPQ-NTSLDElvVFWQ---NQDKVLYELYtgseNPH---NVHPMYKGRTSFDLGSW---TLK 95
Cdd:cd05886    7 DSMSGFIGTDVVLHCSFANPLpSVKITQ--VTWQkstNGSKQNVAIY----NPSmgvSVLPPYRERVTFLNPSFtdgTIR 80

                         90
                 ....*....|....
gi 829986063  96 LHNIEIKDEGTYYC 109
Cdd:cd05886   81 LSRLELEDEGVYIC 94

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 829986063  30 AYFGDTGLLPCRFKNPQntslDELVVFWQN-QDKVLYELYTGSENpH--NVHPMYKGRTSF---DLGSWTLKLHNIEIKD 103
Cdd:cd05846   10 AVLGGNATLSCNLTLPE----EVLQVTWQKiKASSPENIVTYSKK-YgvKIQPSYVRRISFtssGLNSTSITIWNVTLED 84

                 ....*.
gi 829986063 104 EGTYYC 109
Cdd:cd05846   85 EGCYKC 90