P51654C9JLE3G3V1R0Q2L880Q2L882GPC3_HUMANGlypican-3GTR2-2Intestinal protein OCI-5MXR7Glypican-3 alpha subunitGlypican-3 beta subunitGPC3OCI5Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoMapping of the Simpson-Golabi-Behmel overgrowth syndrome gene (GPC3) to chromosome X in human and rat by fluorescence in situ hybridization.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)TISSUE SPECIFICITYDISEASECloning and characterization of human cDNAs encoding a protein with high homology to rat intestinal development protein OCI-5.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)Expression of the Glypican-3 protein in hepatoma cells.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3)VARIANT MET-429The DNA sequence of the human X chromosome.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Analysis of exon/intron structure and 400 kb of genomic sequence surrounding the 5'-promoter and 3'-terminal ends of the human glypican 3 (GPC3) gene.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma.MARKER FOR HEPATOCELLULAR CARCINOMAProcessing by proprotein convertases is required for glypican-3 modulation of cell survival, Wnt signaling, and gastrulation movements.FUNCTIONSUBUNITINTERACTION WITH WNT5ASUBCELLULAR LOCATIONGLYCOSYLATIONCLEAVAGEMUTAGENESIS OF 355-ARG--ARG-358; 370-LYS--LYS-374; 387-ARG--ARG-389 AND 394-LYS--LYS-396Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma.PROTEIN SEQUENCE OF 359-367Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling.ROLE IN HEPATOCELLULAR CARCINOMA GROWTHProcessing by convertases is not required for glypican-3-induced stimulation of hepatocellular carcinoma growth.FUNCTIONINTERACTION WITH WNT3A AND WNT7BMUTAGENESIS OF 355-ARG--ARG-358ROLE IN HEPATOCELLULAR CARCINOMA GROWTHThe Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26.FUNCTIONINTERACTION WITH DPP4Initial characterization of the human central proteome.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling.FUNCTIONINTERACTION WITH FZD4; FZD7 AND FZD8A single kinase generates the majority of the secreted phosphoproteome.PHOSPHORYLATION AT SER-352Processing by convertases is required for glypican-3-induced inhibition of Hedgehog signaling.CLEAVAGEMUTAGENESIS OF 355-ARG--ARG-358Role of glycanation and convertase maturation of soluble glypican-3 in inhibiting proliferation of hepatocellular carcinoma cells.GLYCOSYLATION AT ASN-124; ASN-241 AND ASN-418PYROGLUTAMATE FORMATION AT GLN-25IDENTIFICATION BY MASS SPECTROMETRYAn affinity chromatography and glycoproteomics workflow to profile the chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in the placenta and in cancer.TISSUE SPECIFICITYGLYCOSYLATIONMutational analysis of the GPC3/GPC4 glypican gene cluster on Xq26 in patients with Simpson-Golabi-Behmel syndrome: identification of loss-of-function mutations in the GPC3 gene.VARIANT SGBS1 ARG-296Cell surface proteoglycan (PubMed:14610063). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (By similarity). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (By similarity). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (PubMed:16227623, PubMed:24496449). Positively regulates the non-canonical Wnt signaling pathway (By similarity). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Inhibits the dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (By similarity). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By similarity). Required for coronary vascular development (By similarity). Plays a role in regulating cell movements during gastrulation (By similarity).Heterodimer; disulfide-linked (PubMed:14610063). Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer (PubMed:14610063). Interacts with DPP4 (PubMed:17549790). Interacts with FGF2 (By similarity). Interacts with WNT5A (PubMed:14610063). Also interacts with WNT3A and WNT7B (PubMed:16227623). Interacts with hedgehog protein SHH; the heparan sulfate chains are not required for the interaction (By similarity). Also interacts with hedgehog protein IHH (By similarity). Interacts with CD81 (By similarity). Interacts with Wnt receptors FZD4, FZD7 and FZD8; the heparan sulfate chains are required for the interaction (PubMed:24496449).Cell membraneLipid-anchorGPI-anchorExtracellular sideP51654-11P51654-22Variant BP51654-33Variant CDetected in placenta (at protein level) (PubMed:32337544). Highly expressed in lung, liver and kidney.O-glycosylated; contains heparan sulfate and/or chondroitin sulfate.Cleaved intracellularly by a furin-like convertase to generate 2 subunits, alpha and beta, which remain associated through disulfide bonds and are associated with the cell surface via the GPI-anchor (PubMed:14610063). This processing is essential for its role in inhibition of hedgehog signaling (PubMed:25653284). A second proteolytic event may result in cleavage of the protein on the cell surface, separating it from the GPI-anchor and leading to its shedding from the cell surface (PubMed:14610063).Simpson-Golabi-Behmel syndrome 1
SGBS1
A condition characterized by pre- and postnatal overgrowth (gigantism), facial dysmorphism and a variety of inconstant visceral and skeletal malformations. Characteristic dysmorphic features include macrocephaly with coarse, distinctive facies with a large protruding jaw, broad nasal bridge and cleft palate. Cardiac defects are frequent.The disease is caused by variants affecting the gene represented in this entry.Used as a marker for hepatocellular carcinoma (HCC) as it is expressed in HCC but is not detectable in hepatocytes from normal or benign liver diseases (PubMed:12851874). When attached to the cell surface, stimulates the growth of HCC cells by increasing canonical Wnt signaling (PubMed:16024626). Cleavage is not required for stimulation of Wnt signaling or HCC growth (PubMed:16227623).Belongs to the glypican family.3D-structureAlternative splicingCell membraneDirect protein sequencingDisease variantDisulfide bondGlycoproteinGPI-anchorHeparan sulfateLipoproteinMembranePhosphoproteinProtease inhibitorProteoglycanPyrrolidone carboxylic acidReference proteomeSignalTTETEKKIWHFKYPIFFLCIGLDLQWRVMRQYRAQYARARAKVLKAVLARRRAAAKLKALAMAGTVRTACLVVAMLLSLDFPGQAQPPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQLMNPGLPDSALDINECLRGARRDLKVFGNFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNAGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKVLKVAHVEHEETLSSRRRELIQKLKSFISFYSALPGYICSHSPVAENDTLCWNGQELVERYSQKAARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSMPKGRVLDKNLDEEGFESGDCGDDEDECIGGSGDGMIKVKNQLRFLAELAYDLDVDDAPGNSQQATPKDNEISTFHNLGNVHSPLKLLTSMAISVVCFFFLVH
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