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 18857971  81 TLNISTQLSSSVYLHCRVNDLQGKTVSWMRRRGDdltLITFGQHTYSGDSRYSLEFEEPNDWKLLIQFANERDEGPYECQ 160
Cdd:cd05717   3 TQDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQ---TIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCL 79

                        90
                ....*....|....*
gi 18857971 161 VSSHPPLVLLVYLTI 175
Cdd:cd05717  80 HYTDPVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18857971   198 GSTIELQCVISKIPHPSsyITWRHGPRLLNYDTSRGGISVKTDmlpgralSRLYIANANRQDTGNYTC 265
Cdd:pfam13927  16 GETVTLTCEATGSPPPT--ITWYKNGEPISSGSTRSRSLSGSN-------STLTISNVTRSDAGTYTC 74

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to 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-1, Necl-2, and Necl-3 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue, and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Necl-3 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971  81 TLNISTQLSSSVYLHCRVNDLQGKTVSWMRRRGDdltLITFGQHTYSGDSRYSLEFEEPNDWKLLIQFANERDEGPYECQ 160
Cdd:cd05717   3 TQDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQ---TIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCL 79

                        90
                ....*....|....*
gi 18857971 161 VSSHPPLVLLVYLTI 175
Cdd:cd05717  80 HYTDPVSTKKVTVTV 94

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971    83 NISTQLSSSVYLHCRVndlQGK---TVSWMRrrgDDLTLitfgqhtySGDSRYSLEFEEpNDWKLLIQFANERDEGPYEC 159
Cdd:pfam07679   9 DVEVQEGESARFTCTV---TGTpdpEVSWFK---DGQPL--------RSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTC 73

                  ...
gi 18857971   160 QVS 162
Cdd:pfam07679  74 VAT 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18857971   198 GSTIELQCVISKIPHPSsyITWRHGPRLLNYDTSRGGISVKTDmlpgralSRLYIANANRQDTGNYTC 265
Cdd:pfam13927  16 GETVTLTCEATGSPPPT--ITWYKNGEPISSGSTRSRSLSGSN-------STLTISNVTRSDAGTYTC 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18857971 201 IELQCVISKIPHPSsyITWRHGPRLLNYDTSRGGISVKTDmlpgralSRLYIANANRQDTGNYTCMLGNEITETVVVHV 279
Cdd:cd00096   1 VTLTCSASGNPPPT--ITWYKNGKPLPPSSRDSRRSELGN-------GTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971 176 IVPHVEILDergsatpekyykAGSTIELQCVISKipHPSSYITWRHGPRLLNYDtSRGGISVKtdmlpgralSRLYIANA 255
Cdd:cd20957   6 IDPPVQTVD------------FGRTAVFNCSVTG--NPIHTVLWMKDGKPLGHS-SRVQILSE---------DVLVIPSV 61

                        90
                ....*....|....*
gi 18857971 256 NRQDTGNYTCMLGNE 270
Cdd:cd20957  62 KREDKGMYQCFVRND 76

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 18857971 196 KAGSTIELQCVISKIPHPSsyITWRHGPRLLnydTSRGGISVKTDmlpgralSRLYIANANRQDTGNYTCMLGNEITE-- 273
Cdd:cd20978  14 KGGQDVTLPCQVTGVPQPK--ITWLHNGKPL---QGPMERATVED-------GTLTIINVQPEDTGYYGCVATNEIGDiy 81

                ....*..
gi 18857971 274 -TVVVHV 279
Cdd:cd20978  82 tETLLHV 88

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971 191 PEKYYKAGSTIELQCVISKIPHPSsyITW-RHGPRLLNYDTSRGGISVKTDMLpgralsrLYIANANRQDTGNYTCMLGN 269
Cdd:cd05729  12 REHALPAANKVRLECGAGGNPMPN--ITWlKDGKEFKKEHRIGGTKVEEKGWS-------LIIERAIPRDKGKYTCIVEN 82

                ....
gi 18857971 270 EITE 273
Cdd:cd05729  83 EYGS 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971     83 NISTQLSSSVYLHCRVNDLQGKTVSWMRrrgDDLTLITFgqhtysgDSRYSLEfEEPNDWKLLIQFANERDEGPYECQVS 162
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYK---QGGKLLAE-------SGRFSVS-RSGSTSTLTISNVTPEDSGTYTCAAT 71

                   .
gi 18857971    163 S 163
Cdd:smart00410  72 N 72

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. 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 hemolymph protein hemolin, 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 18857971 198 GSTIELQCVISKIPHPSsyITWRHGPRLLNYDTSRGGISVKTdmlpgralSRLYIANANRQDTGNYTCMLGN---EITET 274
Cdd:cd20976  16 GQDFVAQCSARGKPVPR--ITWIRNAQPLQYAADRSTCEAGV--------GELHIQDVLPEDHGTYTCLAKNaagQVSCS 85

                ....*
gi 18857971 275 VVVHV 279
Cdd:cd20976  86 AWVTV 90

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 18857971   188 SATPEKYYKAGSTIELQCvISKIPHPSSYITWRHGprllnyDTSRGGISVKTDMLPGRALSRLYIANANRQDTGNYTCML 267
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTC-SASTGSPGPDVTWSKE------GGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVV 73

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971 198 GSTIELQCVISKIPHPssYITW---------RHGPRLLNYDTSRGGISVKTDMLPgralSRLYIANANRQDTGNYTCMLG 268
Cdd:cd04974  16 GSDVEFHCKVYSDAQP--HIQWlkhvevngsKYGPDGLPYVTVLKVAGVNTTGEE----NTLTISNVTFDDAGEYICLAG 89

                ....
gi 18857971 269 NEIT 272
Cdd:cd04974  90 NSIG 93

T-cell receptor Mu, Heavy chain, variable (V) domain; The members here are composed of the immunoglobulin (Ig) heavy chain (H), variable (V) domain of the T-cell receptor Mu. 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. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971 183 LDERGSATpekyYKAGSTIELQCVISKIPHPSSYITWR-----HGPRLLnydTSRGGISVKTDmlPGRALSR-------- 249
Cdd:cd16095   4 LEESGGGS----HPAGKTLSLKCQTSGFQFNTSQLSWYlwvpgHAPLWL---TSLDHISTKVS--EDRITSSredtnsqi 74

                        90
                ....*....|....*..
gi 18857971 250 -LYIANANRQDTGNYTC 265
Cdd:cd16095  75 fLQIKGLGLRDSGQYHC 91

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18857971    83 NISTQLSSSVYLHCRVndlQGK---TVSWMRrrgDDLTLitfgqhtySGDSRYSLEFEEpNDWKLLIQFANERDEGPYEC 159
Cdd:pfam07679   9 DVEVQEGESARFTCTV---TGTpdpEVSWFK---DGQPL--------RSSDRFKVTYEG-GTYTLTISNVQPDDSGKYTC 73

                  ...
gi 18857971   160 QVS 162
Cdd:pfam07679  74 VAT 76