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 180164    29 VQQSPHCTTVPVGASVNITCSTSGGLRGIYL---RQ-LGPQPQDIIYYeDGVVPTTDRRFRGRIDFSGSQDNL-TITMHR 103
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTYIywyRQkPGQGPEFLIYL-SSSKGKTKGGVPGRFSGSRDGTSSfSLTISN 79

                        90       100       110
                ....*....|....*....|....*....|..
gi 180164   104 LQLSDTGTYTCQAITEVNVY----GSGTLVLV 131
Cdd:cd00099  80 LQPEDSGTYYCAVSESGGTDkltfGSGTRLTV 111

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 180164    29 VQQSPHCTTVPVGASVNITCSTSGGLRGIYL---RQ-LGPQPQDIIYYeDGVVPTTDRRFRGRIDFSGSQDNL-TITMHR 103
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTYIywyRQkPGQGPEFLIYL-SSSKGKTKGGVPGRFSGSRDGTSSfSLTISN 79

                        90       100       110
                ....*....|....*....|....*....|..
gi 180164   104 LQLSDTGTYTCQAITEVNVY----GSGTLVLV 131
Cdd:cd00099  80 LQPEDSGTYYCAVSESGGTDkltfGSGTRLTV 111

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha 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 represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of 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 180164    29 VQQSPHCTTVPVGASVNITC--STSGglrGIYL---RQL-GPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQDNLTITmh 102
Cdd:cd04983   1 VTQSPQSLSVQEGENVTLNCnySTST---FYYLfwyRQYpGQGPQFLIYISSDSGNKKKGRFSATLDKSRKSSSLHIS-- 75

                        90       100       110
                ....*....|....*....|....*....|....
gi 180164   103 RLQLSDTGTYTC----QAITEVNVYGSGTLVLVT 132
Cdd:cd04983  76 AAQLSDSAVYFCalseSGGTGKLTFGKGTRLTVE 109

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 180164    28 EVQQSPHCTTVPVGASVNITCSTSGGLRGIYL----RQLGPQPQDIIYYEDGVVPTTDRRFRGridfSGSQDNLTITMHR 103
Cdd:cd04980   2 VMTQSPASLSVSPGERVTISCKASQSISSNYLawyqQKPGQAPKLLIYYASTLHSGVPSRFSG----SGSGTDFTLTISS 77

                        90       100
                ....*....|....*....|....*....
gi 180164   104 LQLSDTGTYTCQAI-TEVNVYGSGTLVLV 131
Cdd:cd04980  78 VEPEDAAVYYCQQGyTFPYTFGGGTKLEI 106

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 180164      28 EVQQSPHCTTVPVGASVNITCSTSGGlrgiylrqlgPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSqdnLTITmhRLQLS 107
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATGS----------PPPTITWYKNGEPISSGSTRSRSLSGSNST---LTIS--NVTRS 67

                  ....*....
gi 180164     108 DTGTYTCQA 116
Cdd:pfam13927  68 DAGTYTCVA 76

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 180164    35 CTTVPVGASVNITCSTSGGlrgiylrqlGPQPQDIIYYEDGVVPTTDRRFRGRIDFSG--SQDNLTITMHRLQLSDTGTY 112
Cdd:cd05715  26 CYTVGDAFSVTWTYQPEGG---------NTTESMFHYSKGKPYILKVGRFKDRVSWAGnpSKKDASIVISNLQFSDNGTY 96

                ...
gi 180164   113 TCQ 115
Cdd:cd05715  97 TCD 99

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 180164    29 VQQSPHCTTVPVGASVNITCSTSGGLRGI--YLRQLGPQPQDIIYYEDGVVPTTDRRFRGRidFSGSQDNLTI---TMHR 103
Cdd:cd05899   1 VTQSPRYLIKRRGQSVTLRCSQKSGHDNMywYRQDPGKGLQLLFYSYGGGLNEEGDLPGDR--FSASRPSLTRsslTIKS 78

                        90       100
                ....*....|....*....|....*...
gi 180164   104 LQLSDTGTYTCQAITEVNVY----GSGT 127
Cdd:cd05899  79 AEPEDSAVYLCASSLGGGADeayfGPGT 106

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 180164    32 SPHCTTVPVGASVNITCS---TSGGLRGIYLRqLGPQPQD---IIYYEDGVVPTTDRRFRGrIDFSGSQDnLTITMHRLQ 105
Cdd:cd16088   5 SPALLVVTEGANATFTCSfsnTSESFVLNWYR-LSPSNQTdklAAFPEDRSQPGQDWRFRV-TQLPNGRD-FHMSVVRAR 81

                        90
                ....*....|..
gi 180164   106 LSDTGTYTCQAI 117
Cdd:cd16088  82 RNDSGTYLCGAI 93

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 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. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 180164    31 QSPHCTTVPVGASVNITCSTSGGlrgiylrqlgPQPQdIIYYEDGV-VPTTDRRFRgridfsgSQDNLTITMHRLQLSDT 109
Cdd:cd20952   4 QGPQNQTVAVGGTVVLNCQATGE----------PVPT-ISWLKDGVpLLGKDERIT-------TLENGSLQIKGAEKSDT 65

                ....*....
gi 180164   110 GTYTCQAIT 118
Cdd:cd20952  66 GEYTCVALN 74

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 180164    41 GASVNITCSTSGGLRGIY----LRQlgPQPQDI----IYYEDGVVPTTDRRFRGRIDFS--GSQDNLTITMHRLQLSDTG 110
Cdd:cd04981  13 GQSLKLSCKASGFTFTSYgmgwVRQ--APGKGLewigLIYPGGGDTYYADSFKGRFTITrdTSKSTAYLQLNSLTSEDTA 90

                        90       100
                ....*....|....*....|....*...
gi 180164   111 TYTCQAITE------VNVYGSGTLVLVT 132
Cdd:cd04981  91 VYYCARGLGgygysyFDYWGQGTTVTVS 118

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). 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), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; 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" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 180164    27 QEVQQSPHCTTVPvGASVNITCS-TSGGLRGI----YLRQLGPQPQDIIYYEDGVVPTTDRRFRGRIDFSGSQ---DNLT 98
Cdd:cd05718   1 QRVQVPTEVTGFL-GGSVTLPCSlTSPGTTKItqvtWMKIGAGSSQNVAVFHPQYGPSVPNPYAERVEFLAARlglRNAT 79

                        90       100
                ....*....|....*....|
gi 180164    99 ITMHRLQLSDTGTYTCQAIT 118
Cdd:cd05718  80 LRIRNLRVEDEGNYICEFAT 99

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
                ....*....|....*....|....*....|....*....|....*
gi 180164    83 RFRGRIDFSGSQ-DNLTITMHRLQLSDTGTYTCqaitEVNVYGSG 126
Cdd:cd05846  58 SYVRRISFTSSGlNSTSITIWNVTLEDEGCYKC----LFNTFPDG 98