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 185959    22 IQMTQSPSSLSASVGDRVTITCRASQGI-SNNLNWYQQKPGKTPKLLIYAAPSLQSGIPSRFSDSGSGADYTLTIRSLQP 100
Cdd:cd04980   1 IVMTQSPASLSVSPGERVTISCKASQSIsSNYLAWYQQKPGQAPKLLIYYASTLHSGVPSRFSGSGSGTDFTLTISSVEP 80

                ....*.
gi 185959   101 EDFATY 106
Cdd:cd04980  81 EDAAVY 86

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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 composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    22 IQMTQSPSSLSASVGDRVTITCRASQGI-SNNLNWYQQKPGKTPKLLIYAAPSLQSGIPSRFSDSGSGADYTLTIRSLQP 100
Cdd:cd04980   1 IVMTQSPASLSVSPGERVTISCKASQSIsSNYLAWYQQKPGQAPKLLIYYASTLHSGVPSRFSGSGSGTDFTLTISSVEP 80

                ....*.
gi 185959   101 EDFATY 106
Cdd:cd04980  81 EDAAVY 86

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 185959      26 QSPSSLSASVGDRVTITCRASQGISNN---LNWYQQKPGKTPKLLIYAAPSLQ--SGIPSRFS--DSGSGADYTLTIRSL 98
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSMSEAstsVYWYRQPPGKGPTFLIAYYSNGSeeGVKKGRFSgrGDPSNGDGSLTIQNL 80

                  ....*...
gi 185959      99 QPEDFATY 106
Cdd:pfam07686  81 TLSDSGTY 88

Immunoglobulin (Ig) light chain, kappa type, variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, kappa type, variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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 composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which seem to be functionally identical, and can associate with any of the heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    22 IQMTQSPSSLSASVGDRVTITCRASQGI-SNNLNWYQQKPGKTPKLLIYAAPSLQSGIPSRFSDSGSGADYTLTIRSLQP 100
Cdd:cd04980   1 IVMTQSPASLSVSPGERVTISCKASQSIsSNYLAWYQQKPGQAPKLLIYYASTLHSGVPSRFSGSGSGTDFTLTISSVEP 80

                ....*.
gi 185959   101 EDFATY 106
Cdd:cd04980  81 EDAAVY 86

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 185959    24 MTQSPSSLSASVGDRVTITCRASQGISNN-LNWYQQKPGKTPKLLIYAAPSLQS---GIPSRFSDSGSGA-DYTLTIRSL 98
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTyIYWYRQKPGQGPEFLIYLSSSKGKtkgGVPGRFSGSRDGTsSFSLTISNL 80

                ....*...
gi 185959    99 QPEDFATY 106
Cdd:cd00099  81 QPEDSGTY 88

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 185959       28 PSSLSASVGDRVTITCRASQGISNNLNWYQQKpgktPKLLIYaapslqsgiPSRFSDSGSGADYTLTIRSLQPEDFATY 106
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQG----GKLLAE---------SGRFSVSRSGSTSTLTISNVTPEDSGTY 66

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) beta chain; The members here are composed of the immunoglobulin (Ig) variable domain of the beta chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. This group includes the variable domain of the alpha chain of alpha/beta TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    25 TQSPSSLSASVGDRVTITCRASQGiSNNLNWYQQKPGKTPKLLIYAAPSLQ---SGIP-SRFSDSGSGADY-TLTIRSLQ 99
Cdd:cd05899   2 TQSPRYLIKRRGQSVTLRCSQKSG-HDNMYWYRQDPGKGLQLLFYSYGGGLneeGDLPgDRFSASRPSLTRsSLTIKSAE 80

                ....*..
gi 185959   100 PEDFATY 106
Cdd:cd05899  81 PEDSAVY 87

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 185959    24 MTQSPSSLSASVGDRVTITCRASqGISNN---LNWYQQKPGKTPKLLIY----AAPSLQSGIPS-RFS---DSGSgADYT 92
Cdd:cd04982   1 LEQPQLSITREESKSVTISCKVS-GIDFSttyIHWYRQKPGQALERLLYvsstSAVRKDSGKTKnKFEarkDVGK-STST 78

                        90
                ....*....|....
gi 185959    93 LTIRSLQPEDFATY 106
Cdd:cd04982  79 LTITNLEKEDSATY 92

Immunoglobulin (Ig)-like variable (V) domain of Cluster of Differentiation (CD) 8 alpha chain; The members here are composed of the immunoglobulin (Ig)-like variable domain of the Cluster of Differentiation (CD) 8 alpha. The CD8 glycoprotein plays an essential role in the control of T-cell selection, maturation, and the T-cell receptor (TCR)-mediated response to peptide antigen. CD8 is comprised of alpha and beta subunits and is expressed as either an alpha/alpha or alpha/beta dimer. Both dimeric isoforms can serve as a coreceptor for T cell activation and differentiation, however they have distinct physiological roles, different cellular distributions, unique binding partners, etc. Each CD8 subunit is comprised of an extracellular domain containing a V-type Ig-like domain, a single pass transmembrane portion, and a short intracellular domain. The Ig domain of CD8 alpha binds to antibodies. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    27 SPSSLSASVGDRVTITCRASQGISNNLNWYQQKPGKTPKL--LIYAAPSLQSGIP-----SRFSDSGSGADYTLTIRSLQ 99
Cdd:cd05720   4 SPRKRDAQLGQKVELVCEVLNSVPQGCSWLFQPRGSAPQPtfLLYLSSSNKTKWAegldsKRFSGSRSGSSYVLTLKDFR 83

                ....*..
gi 185959   100 PEDFATY 106
Cdd:cd05720  84 KEDEGYY 90

Immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1); The members here are composed of the immunoglobulin (Ig)-like domain of Programmed Cell Death 1 (PD1; also known as CD279/cluster of differentiation 279). PD1 is a cell surface receptor that is expressed on T cells and pro-B cells. The protein's structure includes an extracellular IgV domain followed by a transmembrane region and an intracellular tail. Activation of CD4+ T cells, CD8+ T cells, NKT cells, B cells, and monocytes induces PD-1 expression, immediately after which it binds two distinct ligands, PD-L1 (also known as B7-H1 or CD274/cluster of differentiation 274) and PD-L2, also known as B7-DC. PD-1 plays an important role in down regulating the immune system by preventing the activation of T-cells, reducing autoimmunity and promoting self-tolerance. The inhibitory effect of PD-1 is accomplished by promoting apoptosis in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells. A class of drugs that target PD-1, known as the PD-1 inhibitors, activate the immune system to attack tumors and treat cancer. Comparisons between the mouse PD-1 (mPD-1) and human PD-1 (hPD-1) reveals that unlike the mPD-1 which has a conventional IgSF V-set domain, hPD-1 lacks a C" strand, and instead the C' and D strands are connected by a long and flexible loop. In addition, the BC loop is not stabilized by disulfide bonding to the F strand of the ligand binding beta sheet. These differences result in different binding affinities of human and mouse PD-1 for their ligands.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    25 TQSPSSLSASVGDRVTITCR-ASQGISNNLNWYQQKPG-KTPKLLIYAAPSLQSGIPSRF--SDSGSGADYTLTIRSLQP 100
Cdd:cd16088   3 TFSPALLVVTEGANATFTCSfSNTSESFVLNWYRLSPSnQTDKLAAFPEDRSQPGQDWRFrvTQLPNGRDFHMSVVRARR 82

                ....*.
gi 185959   101 EDFATY 106
Cdd:cd16088  83 NDSGTY 88

Immunoglobulin (Ig) heavy chain (H), variable (V) domain; The members here are composed of the immunoglobulin (Ig) heavy chain (H), variable (V) domain. This group contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology. 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. There are five types of heavy chains (alpha, gamma, delta, epsilon, and mu), which determines the type of immunoglobulin formed: IgA, IgG, IgD, IgE, and IgM, respectively. In higher vertebrates, there are two types of light chain, designated kappa and lambda, which can associate with any of the heavy chains. This family includes alpha, gamma, delta, epsilon, and mu heavy chains.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    36 GDRVTITCRASQGI--SNNLNWYQQKPGKTPKLL---------IYAAPSLQSgipsRFS---DSGSGADYtLTIRSLQPE 101
Cdd:cd04981  13 GQSLKLSCKASGFTftSYGMGWVRQAPGKGLEWIgliypgggdTYYADSFKG----RFTitrDTSKSTAY-LQLNSLTSE 87

                ....*
gi 185959   102 DFATY 106
Cdd:cd04981  88 DTAVY 92

Immunoglobulin variable domain (IgV) Cluster of Differentiation (CD) 79B; The members here are composed of the immunoglobulin variable domain (IgV) of the Cluster of Differentiation (CD) 79B (also known as CD79b molecule, immunoglobulin-associated beta (Ig-beta), and B29). The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described. 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 185959    26 QSPSSLSASVGDRVTITCRASQgiSNNLNWYQQKPGKTPKLLIyaapsLQSGipsRFSDSGSGADYTLTIRSLQPEDFAT 105
Cdd:cd16096   3 QHPRFAAKKRSSMVKFHCYTNY--SGVMTWFRKKGNQRPQELF-----PEDG---RISQTQNGSVYTLTIQNIQYEDNGI 72

                .
gi 185959   106 Y 106
Cdd:cd16096  73 Y 73

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 185959      26 QSPSSLSASVGDRVTITCRASQGISN-NLNWYQQKPGKTPKLLIyaapslqsgipsrFSDSGSGADYTLTIRSLQPEDFA 104
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGpDVTWSKEGGTLIESLKV-------------KHDNGRTTQSSLLISNVTKEDAG 67

                  ..
gi 185959     105 TY 106
Cdd:pfam00047  68 TY 69