GPC3_HUMAN
ID GPC3_HUMAN Reviewed; 580 AA.
AC P51654; C9JLE3; G3V1R0; Q2L880; Q2L882;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Glypican-3;
DE AltName: Full=GTR2-2;
DE AltName: Full=Intestinal protein OCI-5;
DE AltName: Full=MXR7;
DE Contains:
DE RecName: Full=Glypican-3 alpha subunit {ECO:0000303|PubMed:14610063};
DE Contains:
DE RecName: Full=Glypican-3 beta subunit {ECO:0000303|PubMed:14610063};
DE Flags: Precursor;
GN Name=GPC3; Synonyms=OCI5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9021160; DOI=10.1007/s003359900357;
RA Shen T., Sonoda G., Hamid J., Li M., Filmus J., Buick R.N., Testa J.R.;
RT "Mapping of the Simpson-Golabi-Behmel overgrowth syndrome gene (GPC3) to
RT chromosome X in human and rat by fluorescence in situ hybridization.";
RL Mamm. Genome 8:72-72(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP AND DISEASE.
RC TISSUE=Embryo;
RX PubMed=8589713; DOI=10.1038/ng0396-241;
RA Pilia G., Hughes-Benzie R.M., Mackenzie A., Baybayan P., Chen E.Y.,
RA Huber R., Neri G., Cao A., Forabosco A., Schlessinger D.;
RT "Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel
RT overgrowth syndrome.";
RL Nat. Genet. 12:241-247(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9133586; DOI=10.1016/s0378-1119(96)00689-0;
RA Lage H., Dietel M.;
RT "Cloning and characterization of human cDNAs encoding a protein with high
RT homology to rat intestinal development protein OCI-5.";
RL Gene 188:151-156(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND VARIANT MET-429.
RA Grozdanov P.N., Yovchev M.I., Dabeva M.D.;
RT "Expression of the Glypican-3 protein in hepatoma cells.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58.
RX PubMed=9339360; DOI=10.1006/geno.1997.4916;
RA Huber R., Crisponi L., Mazzarella R., Chen C.N., Su Y., Shizuya H.,
RA Chen E.Y., Cao A., Pilia G.;
RT "Analysis of exon/intron structure and 400 kb of genomic sequence
RT surrounding the 5'-promoter and 3'-terminal ends of the human glypican 3
RT (GPC3) gene.";
RL Genomics 45:48-58(1997).
RN [8]
RP MARKER FOR HEPATOCELLULAR CARCINOMA.
RX PubMed=12851874; DOI=10.1016/s0016-5085(03)00689-9;
RA Capurro M., Wanless I.R., Sherman M., Deboer G., Shi W., Miyoshi E.,
RA Filmus J.;
RT "Glypican-3: a novel serum and histochemical marker for hepatocellular
RT carcinoma.";
RL Gastroenterology 125:89-97(2003).
RN [9]
RP FUNCTION, SUBUNIT, INTERACTION WITH WNT5A, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, CLEAVAGE, AND MUTAGENESIS OF 355-ARG--ARG-358;
RP 370-LYS--LYS-374; 387-ARG--ARG-389 AND 394-LYS--LYS-396.
RX PubMed=14610063; DOI=10.1083/jcb.200302152;
RA De Cat B., Muyldermans S.Y., Coomans C., Degeest G., Vanderschueren B.,
RA Creemers J., Biemar F., Peers B., David G.;
RT "Processing by proprotein convertases is required for glypican-3 modulation
RT of cell survival, Wnt signaling, and gastrulation movements.";
RL J. Cell Biol. 163:625-635(2003).
RN [10]
RP PROTEIN SEQUENCE OF 359-367.
RX PubMed=15059894; DOI=10.1158/0008-5472.can-03-2191;
RA Hippo Y., Watanabe K., Watanabe A., Midorikawa Y., Yamamoto S., Ihara S.,
RA Tokita S., Iwanari H., Ito Y., Nakano K., Nezu J., Tsunoda H., Yoshino T.,
RA Ohizumi I., Tsuchiya M., Ohnishi S., Makuuchi M., Hamakubo T., Kodama T.,
RA Aburatani H.;
RT "Identification of soluble NH2-terminal fragment of glypican-3 as a
RT serological marker for early-stage hepatocellular carcinoma.";
RL Cancer Res. 64:2418-2423(2004).
RN [11]
RP ROLE IN HEPATOCELLULAR CARCINOMA GROWTH.
RX PubMed=16024626; DOI=10.1158/0008-5472.can-04-4244;
RA Capurro M.I., Xiang Y.Y., Lobe C., Filmus J.;
RT "Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating
RT canonical Wnt signaling.";
RL Cancer Res. 65:6245-6254(2005).
RN [12]
RP FUNCTION, INTERACTION WITH WNT3A AND WNT7B, MUTAGENESIS OF
RP 355-ARG--ARG-358, AND ROLE IN HEPATOCELLULAR CARCINOMA GROWTH.
RX PubMed=16227623; DOI=10.1074/jbc.m507004200;
RA Capurro M.I., Shi W., Sandal S., Filmus J.;
RT "Processing by convertases is not required for glypican-3-induced
RT stimulation of hepatocellular carcinoma growth.";
RL J. Biol. Chem. 280:41201-41206(2005).
RN [13]
RP FUNCTION, AND INTERACTION WITH DPP4.
RX PubMed=17549790; DOI=10.1002/pmic.200600654;
RA Davoodi J., Kelly J., Gendron N.H., MacKenzie A.E.;
RT "The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and
RT inhibits the dipeptidyl peptidase activity of CD26.";
RL Proteomics 7:2300-2310(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH FZD4; FZD7 AND FZD8.
RX PubMed=24496449; DOI=10.1242/jcs.140871;
RA Capurro M., Martin T., Shi W., Filmus J.;
RT "Glypican-3 binds to Frizzled and plays a direct role in the stimulation of
RT canonical Wnt signaling.";
RL J. Cell Sci. 127:1565-1575(2014).
RN [16]
RP PHOSPHORYLATION AT SER-352.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [17]
RP CLEAVAGE, AND MUTAGENESIS OF 355-ARG--ARG-358.
RX PubMed=25653284; DOI=10.1074/jbc.m114.612705;
RA Capurro M., Shi W., Izumikawa T., Kitagawa H., Filmus J.;
RT "Processing by convertases is required for glypican-3-induced inhibition of
RT Hedgehog signaling.";
RL J. Biol. Chem. 290:7576-7585(2015).
RN [18]
RP GLYCOSYLATION AT ASN-124; ASN-241 AND ASN-418, PYROGLUTAMATE FORMATION AT
RP GLN-25, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29345911; DOI=10.1021/acs.biochem.7b01208;
RA Saad A., Liet B., Joucla G., Santarelli X., Charpentier J., Claverol S.,
RA Grosset C.F., Trezeguet V.;
RT "Role of glycanation and convertase maturation of soluble glypican-3 in
RT inhibiting proliferation of hepatocellular carcinoma cells.";
RL Biochemistry 57:1201-1211(2018).
RN [19]
RP VARIANT SGBS1 ARG-296.
RX PubMed=10814714; DOI=10.1093/hmg/9.9.1321;
RA Veugelers M., Cat B.D., Muyldermans S.Y., Reekmans G., Delande N.,
RA Frints S., Legius E., Fryns J.-P., Schrander-Stumpel C., Weidle B.,
RA Magdalena N., David G.;
RT "Mutational analysis of the GPC3/GPC4 glypican gene cluster on Xq26 in
RT patients with Simpson-Golabi-Behmel syndrome: identification of loss-of-
RT function mutations in the GPC3 gene.";
RL Hum. Mol. Genet. 9:1321-1328(2000).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate
CC (PubMed:14610063). Negatively regulates the hedgehog signaling pathway
CC when attached via the GPI-anchor to the cell surface by competing with
CC the hedgehog receptor PTC1 for binding to hedgehog proteins (By
CC similarity). Binding to the hedgehog protein SHH triggers
CC internalization of the complex by endocytosis and its subsequent
CC lysosomal degradation (By similarity). Positively regulates the
CC canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled
CC and stimulating the binding of the Frizzled receptor to Wnt ligands
CC (PubMed:16227623, PubMed:24496449). Positively regulates the non-
CC canonical Wnt signaling pathway (By similarity). Binds to CD81 which
CC decreases the availability of free CD81 for binding to the
CC transcriptional repressor HHEX, resulting in nuclear translocation of
CC HHEX and transcriptional repression (By similarity). Inhibits the
CC dipeptidyl peptidase activity of DPP4 (PubMed:17549790). Plays a role
CC in limb patterning and skeletal development by controlling the cellular
CC response to BMP4 (By similarity). Modulates the effects of growth
CC factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (By
CC similarity). Required for coronary vascular development (By
CC similarity). Plays a role in regulating cell movements during
CC gastrulation (By similarity). {ECO:0000250|UniProtKB:Q6V9Y8,
CC ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:14610063,
CC ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:17549790,
CC ECO:0000269|PubMed:24496449}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked (PubMed:14610063). Cleavage by a
CC furin-like convertase results in production of alpha and beta chains
CC which form a disulfide-linked heterodimer (PubMed:14610063). Interacts
CC with DPP4 (PubMed:17549790). Interacts with FGF2 (By similarity).
CC Interacts with WNT5A (PubMed:14610063). Also interacts with WNT3A and
CC WNT7B (PubMed:16227623). Interacts with hedgehog protein SHH; the
CC heparan sulfate chains are not required for the interaction (By
CC similarity). Also interacts with hedgehog protein IHH (By similarity).
CC Interacts with CD81 (By similarity). Interacts with Wnt receptors FZD4,
CC FZD7 and FZD8; the heparan sulfate chains are required for the
CC interaction (PubMed:24496449). {ECO:0000250|UniProtKB:P13265,
CC ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:14610063,
CC ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:17549790,
CC ECO:0000269|PubMed:24496449}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14610063};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P13265}; Extracellular
CC side {ECO:0000250|UniProtKB:P13265}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P51654-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant B;
CC IsoId=P51654-2; Sequence=VSP_046117;
CC Name=3; Synonyms=Variant C;
CC IsoId=P51654-3; Sequence=VSP_046703;
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, liver and kidney.
CC {ECO:0000269|PubMed:8589713}.
CC -!- PTM: O-glycosylated; contains heparan sulfate.
CC {ECO:0000269|PubMed:14610063}.
CC -!- PTM: Cleaved intracellularly by a furin-like convertase to generate 2
CC subunits, alpha and beta, which remain associated through disulfide
CC bonds and are associated with the cell surface via the GPI-anchor
CC (PubMed:14610063). This processing is essential for its role in
CC inhibition of hedgehog signaling (PubMed:25653284). A second
CC proteolytic event may result in cleavage of the protein on the cell
CC surface, separating it from the GPI-anchor and leading to its shedding
CC from the cell surface (PubMed:14610063). {ECO:0000269|PubMed:14610063,
CC ECO:0000269|PubMed:25653284}.
CC -!- DISEASE: Simpson-Golabi-Behmel syndrome 1 (SGBS1) [MIM:312870]: A
CC condition characterized by pre- and postnatal overgrowth (gigantism),
CC facial dysmorphism and a variety of inconstant visceral and skeletal
CC malformations. Characteristic dysmorphic features include macrocephaly
CC with coarse, distinctive facies with a large protruding jaw, broad
CC nasal bridge and cleft palate. Cardiac defects are frequent.
CC {ECO:0000269|PubMed:10814714}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Used as a marker for hepatocellular carcinoma (HCC) as
CC it is expressed in HCC but is not detectable in hepatocytes from normal
CC or benign liver diseases (PubMed:12851874). When attached to the cell
CC surface, stimulates the growth of HCC cells by increasing canonical Wnt
CC signaling (PubMed:16024626). Cleavage is not required for stimulation
CC of Wnt signaling or HCC growth (PubMed:16227623).
CC {ECO:0000269|PubMed:12851874, ECO:0000269|PubMed:16024626,
CC ECO:0000269|PubMed:16227623}.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GPC3ID156.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U50410; AAA93471.1; -; mRNA.
DR EMBL; L47124; AAA98131.1; -; Genomic_DNA.
DR EMBL; L47125; AAA98132.1; -; mRNA.
DR EMBL; L47176; AAB58806.1; -; mRNA.
DR EMBL; Z37987; CAA86069.1; -; mRNA.
DR EMBL; DQ349136; ABC72125.1; -; mRNA.
DR EMBL; DQ349138; ABC72127.1; -; mRNA.
DR EMBL; AL008712; CAI43110.1; -; Genomic_DNA.
DR EMBL; AC002420; CAI43110.1; JOINED; Genomic_DNA.
DR EMBL; AF003529; CAI43110.1; JOINED; Genomic_DNA.
DR EMBL; AL009174; CAI43110.1; JOINED; Genomic_DNA.
DR EMBL; Z99570; CAI43110.1; JOINED; Genomic_DNA.
DR EMBL; AL009174; CAI42761.1; -; Genomic_DNA.
DR EMBL; AC002420; CAI42761.1; JOINED; Genomic_DNA.
DR EMBL; AF003529; CAI42761.1; JOINED; Genomic_DNA.
DR EMBL; AL008712; CAI42761.1; JOINED; Genomic_DNA.
DR EMBL; Z99570; CAI42761.1; JOINED; Genomic_DNA.
DR EMBL; Z99570; CAI42277.1; -; Genomic_DNA.
DR EMBL; AC002420; CAI42277.1; JOINED; Genomic_DNA.
DR EMBL; AF003529; CAI42277.1; JOINED; Genomic_DNA.
DR EMBL; AL008712; CAI42277.1; JOINED; Genomic_DNA.
DR EMBL; AL009174; CAI42277.1; JOINED; Genomic_DNA.
DR EMBL; AL034401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z97196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471107; EAX11771.1; -; Genomic_DNA.
DR EMBL; AF003529; AAB87062.1; -; Genomic_DNA.
DR CCDS; CCDS14638.1; -. [P51654-1]
DR CCDS; CCDS55495.1; -. [P51654-2]
DR CCDS; CCDS55496.1; -. [P51654-3]
DR RefSeq; NP_001158089.1; NM_001164617.1. [P51654-3]
DR RefSeq; NP_001158091.1; NM_001164619.1. [P51654-2]
DR RefSeq; NP_004475.1; NM_004484.3. [P51654-1]
DR AlphaFoldDB; P51654; -.
DR SMR; P51654; -.
DR BioGRID; 108983; 66.
DR DIP; DIP-61509N; -.
DR IntAct; P51654; 24.
DR STRING; 9606.ENSP00000377836; -.
DR ChEMBL; CHEMBL4630889; -.
DR GlyGen; P51654; 6 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P51654; -.
DR PhosphoSitePlus; P51654; -.
DR SwissPalm; P51654; -.
DR BioMuta; GPC3; -.
DR DMDM; 1708022; -.
DR EPD; P51654; -.
DR jPOST; P51654; -.
DR MassIVE; P51654; -.
DR MaxQB; P51654; -.
DR PaxDb; P51654; -.
DR PeptideAtlas; P51654; -.
DR PRIDE; P51654; -.
DR ProteomicsDB; 10697; -.
DR ProteomicsDB; 32411; -.
DR ProteomicsDB; 56359; -. [P51654-1]
DR TopDownProteomics; P51654-1; -. [P51654-1]
DR ABCD; P51654; 57 sequenced antibodies.
DR Antibodypedia; 424; 1355 antibodies from 41 providers.
DR DNASU; 2719; -.
DR Ensembl; ENST00000370818.8; ENSP00000359854.3; ENSG00000147257.16. [P51654-1]
DR Ensembl; ENST00000394299.7; ENSP00000377836.2; ENSG00000147257.16. [P51654-3]
DR Ensembl; ENST00000631057.2; ENSP00000486325.1; ENSG00000147257.16. [P51654-2]
DR GeneID; 2719; -.
DR KEGG; hsa:2719; -.
DR MANE-Select; ENST00000370818.8; ENSP00000359854.3; NM_004484.4; NP_004475.1.
DR UCSC; uc004exe.4; human. [P51654-1]
DR CTD; 2719; -.
DR DisGeNET; 2719; -.
DR GeneCards; GPC3; -.
DR GeneReviews; GPC3; -.
DR HGNC; HGNC:4451; GPC3.
DR HPA; ENSG00000147257; Tissue enriched (placenta).
DR MalaCards; GPC3; -.
DR MIM; 300037; gene.
DR MIM; 312870; phenotype.
DR neXtProt; NX_P51654; -.
DR OpenTargets; ENSG00000147257; -.
DR Orphanet; 654; Nephroblastoma.
DR Orphanet; 373; Simpson-Golabi-Behmel syndrome.
DR PharmGKB; PA28832; -.
DR VEuPathDB; HostDB:ENSG00000147257; -.
DR eggNOG; KOG3821; Eukaryota.
DR GeneTree; ENSGT01050000244955; -.
DR HOGENOM; CLU_024658_4_2_1; -.
DR InParanoid; P51654; -.
DR OMA; EYICSHS; -.
DR PhylomeDB; P51654; -.
DR TreeFam; TF105317; -.
DR PathwayCommons; P51654; -.
DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-3560783; Defective B4GALT7 causes EDS, progeroid type.
DR Reactome; R-HSA-3560801; Defective B3GAT3 causes JDSSDHD.
DR Reactome; R-HSA-3656237; Defective EXT2 causes exostoses 2.
DR Reactome; R-HSA-3656253; Defective EXT1 causes exostoses 1, TRPS2 and CHDS.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-4420332; Defective B3GALT6 causes EDSP2 and SEMDJL1.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; P51654; -.
DR SIGNOR; P51654; -.
DR BioGRID-ORCS; 2719; 10 hits in 695 CRISPR screens.
DR ChiTaRS; GPC3; human.
DR GeneWiki; Glypican_3; -.
DR GenomeRNAi; 2719; -.
DR Pharos; P51654; Tbio.
DR PRO; PR:P51654; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P51654; protein.
DR Bgee; ENSG00000147257; Expressed in upper lobe of left lung and 140 other tissues.
DR ExpressionAtlas; P51654; baseline and differential.
DR Genevisible; P51654; HS.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; TAS:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0060422; F:peptidyl-dipeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl.
DR GO; GO:0010171; P:body morphogenesis; IEA:Ensembl.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0042074; P:cell migration involved in gastrulation; ISS:UniProtKB.
DR GO; GO:0072111; P:cell proliferation involved in kidney development; ISS:UniProtKB.
DR GO; GO:0072203; P:cell proliferation involved in metanephros development; IEA:Ensembl.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; ISS:UniProtKB.
DR GO; GO:0072180; P:mesonephric duct morphogenesis; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045926; P:negative regulation of growth; IEA:Ensembl.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IEA:Ensembl.
DR InterPro; IPR001863; Glypican.
DR InterPro; IPR015501; Glypican-3.
DR InterPro; IPR019803; Glypican_CS.
DR PANTHER; PTHR10822; PTHR10822; 1.
DR PANTHER; PTHR10822:SF4; PTHR10822:SF4; 1.
DR Pfam; PF01153; Glypican; 1.
DR PROSITE; PS01207; GLYPICAN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; GPI-anchor; Heparan sulfate;
KW Lipoprotein; Membrane; Phosphoprotein; Protease inhibitor; Proteoglycan;
KW Pyrrolidone carboxylic acid; Reference proteome; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:29345911"
FT CHAIN 25..358
FT /note="Glypican-3 alpha subunit"
FT /evidence="ECO:0000305|PubMed:14610063"
FT /id="PRO_0000445410"
FT CHAIN 359..554
FT /note="Glypican-3 beta subunit"
FT /evidence="ECO:0000305|PubMed:14610063"
FT /id="PRO_0000445411"
FT PROPEP 555..580
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012310"
FT SITE 358..359
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:14610063,
FT ECO:0000269|PubMed:15059894"
FT MOD_RES 25
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:29345911"
FT MOD_RES 352
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT LIPID 554
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29345911"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29345911"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29345911"
FT CARBOHYD 495
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 509
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT DISULFID 35..72
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 65..262
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 73..265
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 197..349
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 252..285
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 274..422
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 278..410
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT VAR_SEQ 59..112
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_046117"
FT VAR_SEQ 344
FT /note="T -> TETEKKIWHFKYPIFFLCIGLDLQ (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_046703"
FT VARIANT 296
FT /note="W -> R (in SGBS1; dbSNP:rs104894854)"
FT /evidence="ECO:0000269|PubMed:10814714"
FT /id="VAR_021385"
FT VARIANT 429
FT /note="V -> M (in dbSNP:rs11539789)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_069139"
FT MUTAGEN 355..358
FT /note="RQYR->AQYA: Abolishes proteolytic processing.
FT Abolishes interaction with WNT5A and ability to regulate
FT Wnt signaling. Increases binding of hedgehog protein SHH to
FT the PTC1 receptor and abolishes ability to inhibit hedgehog
FT signaling."
FT /evidence="ECO:0000269|PubMed:14610063,
FT ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:25653284"
FT MUTAGEN 355
FT /note="R->A: No effect on proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
FT MUTAGEN 358
FT /note="R->A: No effect on proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
FT MUTAGEN 371..374
FT /note="KVLK->AVLA: No effect on proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
FT MUTAGEN 387..389
FT /note="RRR->AAA: No effect on proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
FT MUTAGEN 394..396
FT /note="KLK->ALA: No effect on proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
SQ SEQUENCE 580 AA; 65563 MW; 19485B76D3CE15FC CRC64;
MAGTVRTACL VVAMLLSLDF PGQAQPPPPP PDATCHQVRS FFQRLQPGLK WVPETPVPGS
DLQVCLPKGP TCCSRKMEEK YQLTARLNME QLLQSASMEL KFLIIQNAAV FQEAFEIVVR
HAKNYTNAMF KNNYPSLTPQ AFEFVGEFFT DVSLYILGSD INVDDMVNEL FDSLFPVIYT
QLMNPGLPDS ALDINECLRG ARRDLKVFGN FPKLIMTQVS KSLQVTRIFL QALNLGIEVI
NTTDHLKFSK DCGRMLTRMW YCSYCQGLMM VKPCGGYCNV VMQGCMAGVV EIDKYWREYI
LSLEELVNGM YRIYDMENVL LGLFSTIHDS IQYVQKNAGK LTTTIGKLCA HSQQRQYRSA
YYPEDLFIDK KVLKVAHVEH EETLSSRRRE LIQKLKSFIS FYSALPGYIC SHSPVAENDT
LCWNGQELVE RYSQKAARNG MKNQFNLHEL KMKGPEPVVS QIIDKLKHIN QLLRTMSMPK
GRVLDKNLDE EGFESGDCGD DEDECIGGSG DGMIKVKNQL RFLAELAYDL DVDDAPGNSQ
QATPKDNEIS TFHNLGNVHS PLKLLTSMAI SVVCFFFLVH
