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 21314764  23 AVLLLNPPWSTAFKGEKVALICSSiSHSLAQGDTYWYHDEKLLKIKHDKIQITE-----PGNYQCKTRGSSLSDAVHVEF 97
Cdd:cd05752   1 AVVSLDPPWTTVFQGEKVTLTCQG-FYSPEQNSTQWYHNGTLISSTSSSYRIVAatvndSGEYRCQTQGSSLSDPVHLEV 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21314764   292 IRPTGGQLIEGENMVLICSVAQGSGTVTFSWHKEGRVRSLGRKTQRSLL----AELHVLTVKESDAGRYYCAADNVHSP 366
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVVNNPGGS 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764   383 PVLtfRAPRAHTVVGDLLELHCESLrGSPPILYRFYHEDVTLgnssapSGGGASFNLSLTAEHSGNYSCDADNGLGAQHS 462
Cdd:pfam13895   2 PVL--TPSPTVVTEGEPVTLTCSAP-GNPPPSYTWYKDGSAI------SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVS 72

                  ....*..
gi 21314764   463 HGVSLRV 469
Cdd:pfam13895  73 NPVELTV 79

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764  23 AVLLLNPPWSTAFKGEKVALICSSiSHSLAQGDTYWYHDEKLLKIKHDKIQITE-----PGNYQCKTRGSSLSDAVHVEF 97
Cdd:cd05752   1 AVVSLDPPWTTVFQGEKVTLTCQG-FYSPEQNSTQWYHNGTLISSTSSSYRIVAatvndSGEYRCQTQGSSLSDPVHLEV 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21314764   292 IRPTGGQLIEGENMVLICSVAQGSGTVTFSWHKEGRVRSLGRKTQRSLL----AELHVLTVKESDAGRYYCAADNVHSP 366
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVVNNPGGS 79

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764   383 PVLtfRAPRAHTVVGDLLELHCESLrGSPPILYRFYHEDVTLgnssapSGGGASFNLSLTAEHSGNYSCDADNGLGAQHS 462
Cdd:pfam13895   2 PVL--TPSPTVVTEGEPVTLTCSAP-GNPPPSYTWYKDGSAI------SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVS 72

                  ....*..
gi 21314764   463 HGVSLRV 469
Cdd:pfam13895  73 NPVELTV 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21314764 286 SNVNLEIRPTGGQLIEGENMVLICSvAQGSGTVTFSWHKEGRVRSLG--RKTQRSLLAELHVLTVKESDAGRYYCAADN 362
Cdd:cd20970   1 PVISTPQPSFTVTAREGENATFMCR-AEGSPEPEISWTRNGNLIIEFntRYIVRENGTTLTIRNIRRSDMGIYLCIASN 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 21314764    487 AVVGDLLELHCESLRGSFPILYWFYHEDDTL---GNISA-HSGGGASFNLS-LTTEHSGNYSCEADNGLGaQHSKVVTLN 561
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVsRSGSTSTLTISnVTPEDSGTYTCAATNSSG-SASSGTTLT 84

                   .
gi 21314764    562 V 562
Cdd:smart00410  85 V 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764   192 PVLRASSSTPIEGSPMTLTCETQLSPqrpdvQLQFSLFRDSQTLglgwSRSPRLQIPAMWTEDSGSYWCEVEtvTHSIKK 271
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAPGNP-----PPSYTWYKDGSAI----SSSPNFFTLSVSAEDSGTYTCVAR--NGRGGK 70

                  ....*....
gi 21314764   272 RSLRSQIRV 280
Cdd:pfam13895  71 VSNPVELTV 79

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 21314764 493 LELHCESLRGSFPILYWfYHEDDTLGNISAHSGGGASFNLSLT-----TEHSGNYSCEADNGLGAQHSKVV 558
Cdd:cd00096   1 VTLTCSASGNPPPTITW-YKNGKPLPPSSRDSRRSELGNGTLTisnvtLEDSGTYTCVASNSAGGSASASV 70

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764  23 AVLLLNPPWSTAFKGEKVALICSSiSHSLAQGDTYWYHDEKLLKIKHDKIQITE-----PGNYQCKTRGSSLSDAVHVEF 97
Cdd:cd05752   1 AVVSLDPPWTTVFQGEKVTLTCQG-FYSPEQNSTQWYHNGTLISSTSSSYRIVAatvndSGEYRCQTQGSSLSDPVHLEV 79

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 21314764   292 IRPTGGQLIEGENMVLICSVAQGSGTVTFSWHKEGRVRSLGRKTQRSLL----AELHVLTVKESDAGRYYCAADNVHSP 366
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVVNNPGGS 79

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21314764   475 RPVLTLRAPGAQAVVGDLLELHCESLRGSFPILYWFYHEDDTLGN---ISAHSGGGASFNL-SLTTEHSGNYSCEADN 548
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGstrSRSLSGSNSTLTIsNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764   289 NLEIRPTGGQLIEGENMVLICSvAQGSGTVTFSWHKEGRVRSlgrKTQRSllaelHVLTVKESDAGRYYCAADNVHSPIL 368
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCS-APGNPPPSYTWYKDGSAIS---SSPNF-----FTLSVSAEDSGTYTCVARNGRGGKV 71

                  ....*...
gi 21314764   369 STWIRVTV 376
Cdd:pfam13895  72 SNPVELTV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764    301 EGENMVLICSVAqGSGTVTFSWHKEGRVRSLGRK----TQRSLLAELHVLTVKESDAGRYYCAADNVHSPILSTwIRVTV 376
Cdd:smart00410   8 EGESVTLSCEAS-GSPPPEVTWYKQGGKLLAESGrfsvSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG-TTLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21314764   109 PVFEGDNVILRCQGKDNKNThQKVYYKDGKQLPNSYNLekiTVNSVSRDNS-KYHCTAyrkfYILDIEVTSKPLNIQV 185
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPP-SYTWYKDGSAISSSPNF---FTLSVSAEDSgTYTCVA----RNGRGGKVSNPVELTV 79

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764    487 AVVGDLLELHCESLRGSFPILYWFYHEDDTL---GNISA-HSGGGASFNLS-LTTEHSGNYSCEADNGLGaQHSKVVTLN 561
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLaesGRFSVsRSGSTSTLTISnVTPEDSGTYTCAATNSSG-SASSGTTLT 84

                   .
gi 21314764    562 V 562
Cdd:smart00410  85 V 85

C17orf99 Ig domain; This Ig domain is found in tandem in the uncharacterized human protein C17orf99, which is found across mammalian species.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764   397 GDLLELHCESLRGSPPILYRFYHED-VTLGNSSAPSGGGASFNLSLTAEHSG---NYSCDADNGLGAQHShgvSLRVTVP 472
Cdd:pfam17736  16 GRRVLISCHASQGSPPITYSLVGSDgIVVAKKIPLHGEPANFSLNITLKSSPdllTYQCQAANTSGTQVS---SLRLQPP 92

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 21314764 306 VLICSVaQGSGTVTFSWHKEGRVRSLGRKTQRSLL---AELHVLTVKESDAGRYYCAADN 362
Cdd:cd00096   2 TLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSElgnGTLTISNVTLEDSGTYTCVASN 60

First 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 first 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 first 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 Ig 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21314764 301 EGENMVLICSVAQGSGTVTFSWHKEGRVRSLGRK--TQRSLLAELHVLTVKESDAGRYYCAADNVH 364
Cdd:cd20979  14 EGQPTVLECVTEGGDQGVKYSWLKDGKSFNWQEHnvAQRKDEGSLVFLKPQASDEGQYQCFAETPA 79

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21314764 292 IRPTGGQLIEGENMVLICSVaQGSGTVTFSWHKEGRVRSLGRKTQ---RSLLAELHVLTVKESDAGRYYCAADNVHS 365
Cdd:cd20949   4 ENAYVTTVKEGQSATILCEV-KGEPQPNVTWHFNGQPISASVADMskyRILADGLLINKVTQDDTGEYTCRAYQVNS 79

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 21314764 400 LELHCESlRGSPPILYRFYHEDVTLGNSSAPSGGGASFNLSLT-----AEHSGNYSCDADNGLGAQHSHGV 465
Cdd:cd00096   1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTisnvtLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21314764 286 SNVNLEIRPTGGQLIEGENMVLICSVAQGSGT-VTFSW----HKEGRVRSLGR--KTQRS----LLAELHVLTVKESDAG 354
Cdd:cd05742   1 SDLELSPNAEPTVLPQGETLVLNCTANVNLNEvVDFQWtypsEKEGKLALLKPdiKVDWSepgeFVSTLTIPEATLKDSG 80

                        90       100
                ....*....|....*....|.
gi 21314764 355 RYYCAA-DNVHSPILSTWIRV 374
Cdd:cd05742  81 TYTCAArSGVMKKEKQTSVSV 101

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 21314764 493 LELHCESLRGSFPILYWfYHEDDTLGNISAHSGGGASFNLSLT-----TEHSGNYSCEADNGLGAQHSKVV 558
Cdd:cd00096   1 VTLTCSASGNPPPTITW-YKNGKPLPPSSRDSRRSELGNGTLTisnvtLEDSGTYTCVASNSAGGSASASV 70

Seventh 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 seventh 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.

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gi 21314764 485 AQAVVGDLLELHCESLRGSFPILYWFYHEDDTLG---------NISAHSGGGASFnLSLTTEHSGNYSCEADNGLGAQHS 555
Cdd:cd20954  11 ANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGeykdllydpNVRILPNGTLVF-GHVQKENEGHYLCEAKNGIGSGLS 89

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gi 21314764 556 KVVTLNV 562
Cdd:cd20954  90 KVIFLKV 96