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 2085060539  52 PYFDlTMPRNITSLVGKSAYLGCRVKHLGNKTVAWiRHRDLHIltvgtytyTTDQRFQTSYhrDIDEWTLQIKWAQQRDA 131
Cdd:pfam07679   1 PKFT-QKPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPL--------RSSDRFKVTY--EGGTYTLTISNVQPDDS 68

                  ....*.
gi 2085060539 132 GVYECQ 137
Cdd:pfam07679  69 GKYTCV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539  209 PDLYVDKGSTINLTCiiKFSPEPPTHIFWYHQDKVLSEETSGgrlkfKTIKSEETKSILLIYDADLLHSGKYSCYPSNTE 288
Cdd:smart00410   2 PSVTVKEGESVTLSC--EASGSPPPEVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 2085060539  289 I---ASIRVHV 296
Cdd:smart00410  75 GsasSGTTLTV 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2085060539 219 INLTCiiKFSPEPPTHIFWYHQDKVLSEETSGGRlkfktiKSEETKSILLIYDADLLHSGKYSCYPSN 286
Cdd:cd00096     1 VTLTC--SASGNPPPTITWYKNGKPLPPSSRDSR------RSELGNGTLTISNVTLEDSGTYTCVASN 60

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 2085060539  62 ITSLVGKSAYLGCRVKHLGNKTVA--WIRHRD-------LHILTVGTYTYTTDQ---RFQTSYHRDIDEWTLQIKWAQQR 129
Cdd:cd04982     8 ITREESKSVTISCKVSGIDFSTTYihWYRQKPgqalerlLYVSSTSAVRKDSGKtknKFEARKDVGKSTSTLTITNLEKE 87

                  ....*..
gi 2085060539 130 DAGVYEC 136
Cdd:cd04982    88 DSATYYC 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539  209 PDLYVDKGSTINLTCiiKFSPEPPTHIFWYHQDKVLSEETSGgrlkfKTIKSEETKSILLIYDADLLHSGKYSCYPSNTE 288
Cdd:smart00410   2 PSVTVKEGESVTLSC--EASGSPPPEVTWYKQGGKLLAESGR-----FSVSRSGSTSTLTISNVTPEDSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 2085060539  289 I---ASIRVHV 296
Cdd:smart00410  75 GsasSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539  52 PYFDlTMPRNITSLVGKSAYLGCRVKHLGNKTVAWiRHRDLHIltvgtytyTTDQRFQTSYhrDIDEWTLQIKWAQQRDA 131
Cdd:pfam07679   1 PKFT-QKPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDGQPL--------RSSDRFKVTY--EGGTYTLTISNVQPDDS 68

                  ....*.
gi 2085060539 132 GVYECQ 137
Cdd:pfam07679  69 GKYTCV 74

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539   59 PRNITSLVGKSAYLGCRVKHLGNKTVAWIRHRDLHILTVGTYTYTtdqrfqtsyhRDIDEWTLQIKWAQQRDAGVYECQI 138
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVS----------RSGSTSTLTISNVTPEDSGTYTCAA 70

                   .
gi 2085060539  139 S 139
Cdd:smart00410  71 T 71

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539 209 PDLYVDKGSTINLTCIIKFSPEPpthIFWYHQDKVLsEETSGGRLKFKTIKSeetksiLLIYDADLLHSGKYSCYPSN-- 286
Cdd:cd04979     4 KQISVKEGDTVILSCSVKSNNAP---VTWIHNGKKV-PRYRSPRLVLKTERG------LLIRSAQEADAGVYECHSGErv 73

                          90
                  ....*....|...
gi 2085060539 287 --TEIASIRVHVL 297
Cdd:cd04979    74 lgSTLRSVTLHVL 86

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539  58 MPRNITSLVGKSAYLGCRVKHLGNKTVAWiRHRDLHILTVGTYTYTTDQRFQ---TSYHrdidEWTLQIKWAQQRDAGVY 134
Cdd:cd07701     3 LTQNVTVVEGGTANLTCRVDQNDNTSLQW-SNPAQQTLYFDDKKALRDNRIElvrASWH----ELSISISDVSLSDEGQY 77

                          90
                  ....*....|....*....
gi 2085060539 135 ECQISTQPVRSYSVNLNIV 153
Cdd:cd07701    78 TCSLFTMPVKTSKAYLTVL 96

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 2085060539 209 PDLYVDKGSTINLTCiiKFSPEPPTHIFWYHQDK-----VLSEETSGGRLKFK-----TIKSEETKSILLIYDADLLHSG 278
Cdd:cd04983     6 QSLSVQEGENVTLNC--NYSTSTFYYLFWYRQYPgqgpqFLIYISSDSGNKKKgrfsaTLDKSRKSSSLHISAAQLSDSA 83

                  ....
gi 2085060539 279 KYSC 282
Cdd:cd04983    84 VYFC 87

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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. The fourth Ig-like domain of hemolin 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 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, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2085060539 213 VDKGSTINLTCIIKFSPEPptHIFWYHQDKVLSEETsgGRLKFktikseeTKSILLIYDADLLHSGKYSCYPSNtEIASI 292
Cdd:cd20978    13 VKGGQDVTLPCQVTGVPQP--KITWLHNGKPLQGPM--ERATV-------EDGTLTIINVQPEDTGYYGCVATN-EIGDI 80

                  ....*
gi 2085060539 293 RVHVL 297
Cdd:cd20978    81 YTETL 85

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2085060539 210 DLYVDKGSTINLTCIIKFSPEPPTHIFWYH--QDKVLSEETSGGRLKFktIKSEETKSILLIYDADLLHSGKYSCYPSN 286
Cdd:cd23997     2 DVTVAEGSTLWLPCLVPPSDGPRGPLTWSRghPKTPLLSLELGSPGLW--VLVGPLGILLLLPNVSAQMGGFYLCELGN 78