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 47156672   1 TLSLTCTVSGYSISSgYYWGWIRQPPGKGLEWIGSIY-HSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY 79
Cdd:cd04981  15 SLKLSCKASGFTFTS-YGMGWVRQAPGKGLEWIGLIYpGGGDTYYADSFKGRFTITRDTSKSTAYLQLNSLTSEDTAVYY 93

                        90       100
                ....*....|....*....|...
gi 47156672  80 CARDPkkrgaaaGYYYYYGMDVW 102
Cdd:cd04981  94 CARGL-------GGYGYSYFDYW 109

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 47156672   1 TLSLTCTVSGYSISSgYYWGWIRQPPGKGLEWIGSIY-HSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY 79
Cdd:cd04981  15 SLKLSCKASGFTFTS-YGMGWVRQAPGKGLEWIGLIYpGGGDTYYADSFKGRFTITRDTSKSTAYLQLNSLTSEDTAVYY 93

                        90       100
                ....*....|....*....|...
gi 47156672  80 CARDPkkrgaaaGYYYYYGMDVW 102
Cdd:cd04981  94 CARGL-------GGYGYSYFDYW 109

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 47156672     1 TLSLTCTVSGYSISSGYYWGWIRQPPGKGLEWIgsIYHSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYC 80
Cdd:pfam07686  13 SVTLPCTYSSSMSEASTSVYWYRQPPGKGPTFL--IAYYSNGSEEGVKKGRFSGRGDPSNGDGSLTIQNLTLSDSGTYTC 90

                  ....*
gi 47156672    81 ARDPK 85
Cdd:pfam07686  91 AVIPS 95

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 47156672   1 TLSLTCTVSGYSISSgYYWGWIRQPPGKGLEWIGSIY-HSGSTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYY 79
Cdd:cd04981  15 SLKLSCKASGFTFTS-YGMGWVRQAPGKGLEWIGLIYpGGGDTYYADSFKGRFTITRDTSKSTAYLQLNSLTSEDTAVYY 93

                        90       100
                ....*....|....*....|...
gi 47156672  80 CARDPkkrgaaaGYYYYYGMDVW 102
Cdd:cd04981  94 CARGL-------GGYGYSYFDYW 109

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 47156672   1 TLSLTCTVSGYSISSGYYWgwIRQPPGKGLEWIGSIYhSGSTYYNPSLKSRVTISVDTSKnQFSLKLSSVTAADTAVYYC 80
Cdd:cd00099  15 SVTLSCEVSSSFSSTYIYW--YRQKPGQGPEFLIYLS-SSKGKTKGGVPGRFSGSRDGTS-SFSLTISNLQPEDSGTYYC 90

                ..
gi 47156672  81 AR 82
Cdd:cd00099  91 AV 92

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 47156672   1 TLSLTCTvsgYSISSGYYWGWIRQPPGKGLEWIGSIYhsgsTYYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYC 80
Cdd:cd04983  15 NVTLNCN---YSTSTFYYLFWYRQYPGQGPQFLIYIS----SDSGNKKKGRFSATLDKSRKSSSLHISAAQLSDSAVYFC 87

                .
gi 47156672  81 A 81
Cdd:cd04983  88 A 88

Gammadelta T-cell antigen receptor, variable (V) domain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the 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 antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens; they recognize protein antigens directly and without antigen processing, and 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 standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47156672   3 SLTCTVSGYSISSgYYWGWIRQPPGKGLEWIgsiYHSGSTYyNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCAR 82
Cdd:cd20988  17 TLKCSMKGEAISN-YYINWYRKTQGNTMTFI---YREGGIY-GPGFKDNFRGDIDSSNNLAVLKILEASERDEGSYYCAS 91

                .
gi 47156672  83 D 83
Cdd:cd20988  92 D 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47156672      1 TLSLTCTVSGYSISSGYywgWIRQppgkGLEWIGSiyhsgstyynpslKSRvtISVDTSKNQFSLKLSSVTAADTAVYYC 80
Cdd:smart00410  11 SVTLSCEASGSPPPEVT---WYKQ----GGKLLAE-------------SGR--FSVSRSGSTSTLTISNVTPEDSGTYTC 68

                   .
gi 47156672     81 A 81
Cdd:smart00410  69 A 69

Immunoglobulin (Ig) variable (V) domain of Cluster of Differentiation (CD) 8 beta chain; The members here are composed of the immunoglobulin (Ig)-like domain in Cluster of Differentiation (CD) 8 beta. 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47156672   1 TLSLTCTVSGYSISSGYYWGWIRQPPGKG--LEWIGSIYHSGSTYYNPSLKS-RVTISVDTSKNQFSLKLSSVTAADTAV 77
Cdd:cd07700  15 TVKMSCEAKTSPKNTRIYWLRQRQAPSKDshFEFLASWDPSKGIVYGEGVDQeKLIILSDSDSSRYILSLMSVKPEDSGT 94

                ....
gi 47156672  78 YYCA 81
Cdd:cd07700  95 YFCM 98

Immunoglobulin (Ig) lambda light chain variable (V) domain; The members here are composed of the immunoglobulin (Ig) light chain, lambda type, variable (V) domain. 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47156672   1 TLSLTCTVSGYSISsGYYWGWIRQPPGKGLEWIgsIYHSGSTyyNPSLKSRVTISvdTSKNQFSLKLSSVTAADTAVYYC 80
Cdd:cd04984  15 TVTITCTGSSGNIS-GNYVNWYQQKPGSAPRYL--IYEDKHR--PSGIPDRFSGS--KSGNTASLTISGAQTEDEADYYC 87

                .
gi 47156672  81 A 81
Cdd:cd04984  88 Q 88

Immunoglobulin (Ig)-like variable (V) domain of the Signal-Regulatory Protein (SIRP); The members here are composed of the immunoglobulin (Ig)-like domain of the Signal-Regulatory Protein (SIRP). The SIRPs belong to the "paired receptors" class of membrane proteins that comprise several genes coding for proteins with similar extracellular regions, but very different transmembrane/cytoplasmic regions with different (activating or inhibitory) signaling potentials. They are commonly on NK cells, but are also on many myeloid cells. Their extracellular region contains three immunoglobulin superfamily domains, a single V-set, and two C1-set IgSF domains. Their cytoplasmic tails that contain either ITIMs or transmembrane regions have positively charged residues that allow an association with adaptor proteins, such as DAP12/KARAP, containing ITAMs. There are 3 distinct SIRP members: alpha, beta, and gamma. SIRP alpha (also known as CD172a or SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1/Shps-1) is a membrane receptor that interacts with a ligand CD47 expressed on many cells and gives an inhibitory signal through immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic region that interact with phosphatases SHP-1 and SHP-2. SIRP beta has a short cytoplasmic region and associates with a transmembrane adapter protein DAP12 containing immunoreceptor tyrosine-based activation motifs to give an activating signal. SIRP gamma contains a very short cytoplasmic region lacking obvious signaling motifs, but also binds CD47 with much less affinity. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 47156672  51 RVTISVDTSKNQ---FSLKLSSVTAADTAVYYCAR 82
Cdd:cd16097  55 RVTTVSDLTKRNnmdFSIRISNITPADAGTYYCVK 89