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 5921633    1 GLVKPSQTLSLTCAISGDSVSSNSAAWncIRPVPSRGLEWLGRTTYRsKWYNDYAVSVKSRITINPDTSKNQFSLQLNSV 80
Cdd:cd04981   8 GLVKPGQSLKLSCKASGFTFTSYGMGW--VRQAPGKGLEWIGLIYPG-GGDTYYADSFKGRFTITRDTSKSTAYLQLNSL 84

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 5921633   81 TPEDTAVYYCASTTLNWGYekdDAFDIWGQGTMVTVS 117
Cdd:cd04981  85 TSEDTAVYYCARGLGGYGY---SYFDYWGQGTTVTVS 118

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 5921633    1 GLVKPSQTLSLTCAISGDSVSSNSAAWncIRPVPSRGLEWLGRTTYRsKWYNDYAVSVKSRITINPDTSKNQFSLQLNSV 80
Cdd:cd04981   8 GLVKPGQSLKLSCKASGFTFTSYGMGW--VRQAPGKGLEWIGLIYPG-GGDTYYADSFKGRFTITRDTSKSTAYLQLNSL 84

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 5921633   81 TPEDTAVYYCASTTLNWGYekdDAFDIWGQGTMVTVS 117
Cdd:cd04981  85 TSEDTAVYYCARGLGGYGY---SYFDYWGQGTTVTVS 118

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 5921633      2 LVKPSQTLSLTCAISGDSVSSNSAAWNCIRPvPSRGLEWLGRTtyrskWYNDYAVSVKS-RITINPDTSKNQFSLQLNSV 80
Cdd:pfam07686   7 TVALGGSVTLPCTYSSSMSEASTSVYWYRQP-PGKGPTFLIAY-----YSNGSEEGVKKgRFSGRGDPSNGDGSLTIQNL 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 5921633     81 TPEDTAVYYCASTTlnwgyekdDAFDIWGQGTMVTV 116
Cdd:pfam07686  81 TLSDSGTYTCAVIP--------SGEGVFGKGTRLTV 108

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 5921633    1 GLVKPSQTLSLTCAISGDSVSSNSAAWncIRPVPSRGLEWLGRTTYRsKWYNDYAVSVKSRITINPDTSKNQFSLQLNSV 80
Cdd:cd04981   8 GLVKPGQSLKLSCKASGFTFTSYGMGW--VRQAPGKGLEWIGLIYPG-GGDTYYADSFKGRFTITRDTSKSTAYLQLNSL 84

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 5921633   81 TPEDTAVYYCASTTLNWGYekdDAFDIWGQGTMVTVS 117
Cdd:cd04981  85 TSEDTAVYYCARGLGGYGY---SYFDYWGQGTTVTVS 118

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 5921633    2 LVKPSQTLSLTCAISGdSVSSNSAAWncIRPVPSRGLEWLgrtTYRSKWYNDYAVSVKSRITINPDTSKnQFSLQLNSVT 81
Cdd:cd00099   9 SVQEGESVTLSCEVSS-SFSSTYIYW--YRQKPGQGPEFL---IYLSSSKGKTKGGVPGRFSGSRDGTS-SFSLTISNLQ 81

                        90       100       110
                ....*....|....*....|....*....|....*
gi 5921633   82 PEDTAVYYCASTTLNWGYEKddafdIWGQGTMVTV 116
Cdd:cd00099  82 PEDSGTYYCAVSESGGTDKL-----TFGSGTRLTV 111

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5921633       2 LVKPSQTLSLTCAISGDSvssnsaawncirpvpsrglewlgrtTYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVT 81
Cdd:smart00410   5 TVKEGESVTLSCEASGSP-------------------------PPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVT 59

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 5921633      82 PEDTAVYYCASTtlnwgyekDDAFDIWGqGTMVTV 116
Cdd:smart00410  60 PEDSGTYTCAAT--------NSSGSASS-GTTLTV 85

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 5921633   10 SLTCAISGDSVSSNSAAWncIRPVPSRGLEWLgrttYRSKwyNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYY 89
Cdd:cd20988  17 TLKCSMKGEAISNYYINW--YRKTQGNTMTFI----YREG--GIYGPGFKDNFRGDIDSSNNLAVLKILEASERDEGSYY 88

                        90       100
                ....*....|....*....|....*..
gi 5921633   90 CASTTLNWGYEKDDAfdIWGQGTMVTV 116
Cdd:cd20988  89 CASDTPGGGREYDPL--IFGKGTYLTV 113

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 5921633    5 PSQTLSLTCAISGDSVSSNSAAWncIRPVPSRGLEWLGRTTYRSKWYNDYAvSVKSRITINPDTSKNQFSLQLNSVTPED 84
Cdd:cd04982  12 ESKSVTISCKVSGIDFSTTYIHW--YRQKPGQALERLLYVSSTSAVRKDSG-KTKNKFEARKDVGKSTSTLTITNLEKED 88

                        90       100       110
                ....*....|....*....|....*....|...
gi 5921633   85 TAVYYCASttlnWGYEKDDAFDIWGQGTMVTVS 117
Cdd:cd04982  89 SATYYCAY----WESGSGYYIKVFGSGTKLIVT 117

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
                ....*....|....*....|....*....|...
gi 5921633   59 KSRITINPDTSKNQFSLQLNSVTPEDTAVYYCA 91
Cdd:cd07700  66 QEKLIILSDSDSSRYILSLMSVKPEDSGTYFCM 98

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold protodomain 3 and 4; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding. This group contains the protodomains 3 and 4 of the CD19 double Ig domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5921633    3 VKPSQTLSLTCAISGDSVSSNSAAWNCIRPVPSR----GLEWLGRTTYRSKWyndyaVSVksritinpdTSKNQFSLQLN 78
Cdd:cd23998   5 VAPGSTLWLSCGVPPDSGTRGPISWTHVHPKPSNtsllSLELKEDRPAREKW-----VLG---------TLRGGALLLLP 70

                        90
                ....*....|..
gi 5921633   79 SVTPEDTAVYYC 90
Cdd:cd23998  71 RATAQDAGIYHC 82

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 5921633   61 RITINPDTSKNQ---FSLQLNSVTPEDTAVYYC 90
Cdd:cd16097  55 RVTTVSDLTKRNnmdFSIRISNITPADAGTYYC 87