Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947  401 PPTITVSSDRDAaparfVTAGSNVTLRCAAASRPPADITW--------SLADPAEAAVPAGSRLLLPAVGPGHAGTYACL 472
Cdd:pfam13927   1 KPVITVSPSSVT-----VREGETVTLTCEATGSPPPTITWykngepisSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 255652947  473 AAN 475
Cdd:pfam13927  76 ASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947  401 PPTITVSSDRDAaparfVTAGSNVTLRCAAASRPPADITW--------SLADPAEAAVPAGSRLLLPAVGPGHAGTYACL 472
Cdd:pfam13927   1 KPVITVSPSSVT-----VREGETVTLTCEATGSPPPTITWykngepisSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 255652947  473 AAN 475
Cdd:pfam13927  76 ASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947   418 VTAGSNVTLRCAAASRPPADITWSLADPAEAAVPAG---------SRLLLPAVGPGHAGTYACLAANprTGRRRRSLLNL 488
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstSTLTISNVTPEDSGTYTCAATN--SSGSASSGTTL 83

                   ..
gi 255652947   489 TV 490
Cdd:smart00410  84 TV 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 255652947 320 LRLRCLGWGPGRGELSWSRDGRALEaaesEGAETPRMRSEGDQLLIVRPVRSDHA-RYTCRVRSPFGHREAA 390
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLP----PSSRDSRRSELGNGTLTISNVTLEDSgTYTCVASNSAGGSASA 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947  401 PPTITVSSDRDAaparfVTAGSNVTLRCAAASRPPADITW--------SLADPAEAAVPAGSRLLLPAVGPGHAGTYACL 472
Cdd:pfam13927   1 KPVITVSPSSVT-----VREGETVTLTCEATGSPPPTITWykngepisSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCV 75

                  ...
gi 255652947  473 AAN 475
Cdd:pfam13927  76 ASN 78

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947 421 GSNVTLRCAAASRPPADITWSLADPAEAAvpaGSRLLLPAVGPGHAGTYACLAANPRTGRRRRSLLNLTV 490
Cdd:cd20948   10 GENLNLSCHAASNPPAQYSWTINGTFQTS---SQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947   418 VTAGSNVTLRCAAASRPPADITWSLADPAEAAVPAG---------SRLLLPAVGPGHAGTYACLAANprTGRRRRSLLNL 488
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfsvsrsgstSTLTISNVTPEDSGTYTCAATN--SSGSASSGTTL 83

                   ..
gi 255652947   489 TV 490
Cdd:smart00410  84 TV 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 255652947 320 LRLRCLGWGPGRGELSWSRDGRALEaaesEGAETPRMRSEGDQLLIVRPVRSDHA-RYTCRVRSPFGHREAA 390
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLP----PSSRDSRRSELGNGTLTISNVTLEDSgTYTCVASNSAGGSASA 68

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 the MuSK lacks this strand and thus it 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 255652947 300 PLPQLSVQPKAPETEEGAaELRLRCLGWGPGRGELSWSRDGRALEaaesEGAETPRMRSEGDQLLIVRPVRSDHARYTCR 379
Cdd:cd20970    1 PVISTPQPSFTVTAREGE-NATFMCRAEGSPEPEISWTRNGNLII----EFNTRYIVRENGTTLTIRNIRRSDMGIYLCI 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 255652947 317 AAELRLRCLGWGPGRGELSWSRDGRalEAAESEGAETPRMRSEGDQLLIVRPVRSDHARYTCRVRSPFGHREAAADVSV 395
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGK--EFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255652947 421 GSNVTLRCAAASRPPADITW----SLADPAEAAVPAGSR--LLLPAVGPGHAGTYACLAANpRTGR 480
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWlkdnKPLTPPEIGENKKKKwtLSLKNLKPEDSGKYTCHVSN-RAGE 83

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 255652947 421 GSNVTLRCAAASRPPADITWSL---ADPAEAAVP-AGSRLLLPAVGPGHAGTYACLAANPR 477
Cdd:cd05851   16 GQNVTLECFALGNPVPVIRWRKilePMPATAEISmSGAVLKIFNIQPEDEGTYECEAENIK 76

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 the MuSK lacks this strand and thus it 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 255652947 402 PTITVSSDRDAAPARFvtaGSNVTLRCAAASRPPADITWS-------LADPAEAAVPAGSRLLLPAVGPGHAGTYACLAA 474
Cdd:cd20970    1 PVISTPQPSFTVTARE---GENATFMCRAEGSPEPEISWTrngnliiEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIAS 77

                 .
gi 255652947 475 N 475
Cdd:cd20970   78 N 78

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth 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. This group 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 255652947 421 GSNVTLRCAAASRPPADITWSLADpaeAAVPAGSRLL----------------LPAVGPGHAGTYACLAAN 475
Cdd:cd20956   16 GPSVSLKCVASGNPLPQITWTLDG---FPIPESPRFRvgdyvtsdgdvvsyvnISSVRVEDGGEYTCTATN 83

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255652947  306 VQPKAPETEEGAAELRLRCL-GWGPGRGELSWSRDGRALEAAESEgaETPRMRSEG---DQLLIVRPVRSDH-ARYTCRV 380
Cdd:pfam08205   3 IEPPASLLEGEGPEVVATCSsAGGKPAPRITWYLDGKPLEAAETS--SEQDPESGLvtvTSELKLVPSRSDHgQSLTCQV 80

                  ...
gi 255652947  381 RSP 383
Cdd:pfam08205  81 SYG 83