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P51654 (GPC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glypican-3
Alternative name(s):
GTR2-2
Intestinal protein OCI-5
MXR7

Cleaved into the following chain:

  1. Secreted glypican-3
Gene names
Name:GPC3
Synonyms:OCI5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length580 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cell surface proteoglycan that bears heparan sulfate. Inhibits the dipeptidyl peptidase activity of DPP4. May be involved in the suppression/modulation of growth in the predominantly mesodermal tissues and organs. May play a role in the modulation of IGF2 interactions with its receptor and thereby modulate its function. May regulate growth and tumor predisposition. Ref.8

Subunit structure

Interacts with DPP4. Ref.8

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor; Extracellular side By similarity.

Secreted glypican-3: Secretedextracellular space By similarity.

Tissue specificity

Highly expressed in lung, liver and kidney.

Involvement in disease

Simpson-Golabi-Behmel syndrome 1 (SGBS1) [MIM:312870]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.10

Sequence similarities

Belongs to the glypican family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
   Molecular functionProtease inhibitor
   PTMGlycoprotein
GPI-anchor
Heparan sulfate
Lipoprotein
Proteoglycan
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.2. Source: ProtInc

anterior/posterior axis specification

Inferred from electronic annotation. Source: Ensembl

body morphogenesis

Inferred from electronic annotation. Source: Ensembl

bone mineralization

Inferred from electronic annotation. Source: Ensembl

branching involved in ureteric bud morphogenesis

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cell proliferation involved in metanephros development

Inferred from electronic annotation. Source: Ensembl

chondroitin sulfate metabolic process

Traceable author statement. Source: Reactome

coronary vasculature development

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

glycosaminoglycan biosynthetic process

Traceable author statement. Source: Reactome

glycosaminoglycan catabolic process

Traceable author statement. Source: Reactome

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

lung development

Inferred from electronic annotation. Source: Ensembl

mesenchymal cell proliferation involved in ureteric bud development

Inferred from sequence or structural similarity. Source: UniProtKB

mesonephric duct morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

osteoclast differentiation

Inferred from electronic annotation. Source: Ensembl

phototransduction, visible light

Traceable author statement. Source: Reactome

positive regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of Wnt signaling pathway, planar cell polarity pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of endocytosis

Inferred from electronic annotation. Source: Ensembl

positive regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

retinoid metabolic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

anchored component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement PubMed 7657705. Source: ProtInc

lysosomal lumen

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: InterPro

   Molecular_functionpeptidyl-dipeptidase inhibitor activity

Inferred from direct assay Ref.8. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51654-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P51654-2)

Also known as: Variant B;

The sequence of this isoform differs from the canonical sequence as follows:
     59-112: Missing.
Isoform 3 (identifier: P51654-3)

Also known as: Variant C;

The sequence of this isoform differs from the canonical sequence as follows:
     344-344: T → TETEKKIWHFKYPIFFLCIGLDLQ

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – ?Glypican-3PRO_0000012309
Chain25 – ?Secreted glypican-3PRO_0000333844
Propeptide? – 580Removed in mature form PotentialPRO_0000012310

Amino acid modifications

Glycosylation1241N-linked (GlcNAc...) Potential
Glycosylation2411N-linked (GlcNAc...) Potential
Glycosylation4181N-linked (GlcNAc...) Potential
Glycosylation4951O-linked (Xyl...) (heparan sulfate) Potential
Glycosylation5091O-linked (Xyl...) (heparan sulfate) Potential

Natural variations

Alternative sequence59 – 11254Missing in isoform 2.
VSP_046117
Alternative sequence3441T → TETEKKIWHFKYPIFFLCIG LDLQ in isoform 3.
VSP_046703
Natural variant2961W → R in SGBS1. Ref.10
VAR_021385
Natural variant4291V → M. Ref.4
Corresponds to variant rs413112608 [ dbSNP | Ensembl ].
VAR_069139

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 19485B76D3CE15FC

FASTA58065,563
        10         20         30         40         50         60 
MAGTVRTACL VVAMLLSLDF PGQAQPPPPP PDATCHQVRS FFQRLQPGLK WVPETPVPGS 

        70         80         90        100        110        120 
DLQVCLPKGP TCCSRKMEEK YQLTARLNME QLLQSASMEL KFLIIQNAAV FQEAFEIVVR 

       130        140        150        160        170        180 
HAKNYTNAMF KNNYPSLTPQ AFEFVGEFFT DVSLYILGSD INVDDMVNEL FDSLFPVIYT 

       190        200        210        220        230        240 
QLMNPGLPDS ALDINECLRG ARRDLKVFGN FPKLIMTQVS KSLQVTRIFL QALNLGIEVI 

       250        260        270        280        290        300 
NTTDHLKFSK DCGRMLTRMW YCSYCQGLMM VKPCGGYCNV VMQGCMAGVV EIDKYWREYI 

       310        320        330        340        350        360 
LSLEELVNGM YRIYDMENVL LGLFSTIHDS IQYVQKNAGK LTTTIGKLCA HSQQRQYRSA 

       370        380        390        400        410        420 
YYPEDLFIDK KVLKVAHVEH EETLSSRRRE LIQKLKSFIS FYSALPGYIC SHSPVAENDT 

       430        440        450        460        470        480 
LCWNGQELVE RYSQKAARNG MKNQFNLHEL KMKGPEPVVS QIIDKLKHIN QLLRTMSMPK 

       490        500        510        520        530        540 
GRVLDKNLDE EGFESGDCGD DEDECIGGSG DGMIKVKNQL RFLAELAYDL DVDDAPGNSQ 

       550        560        570        580 
QATPKDNEIS TFHNLGNVHS PLKLLTSMAI SVVCFFFLVH 

« Hide

Isoform 2 (Variant B) [UniParc].

Checksum: A0858770AF739C17
Show »

FASTA52659,475
Isoform 3 (Variant C) [UniParc].

Checksum: 1930C0382E91AF60
Show »

FASTA60368,414

References

« Hide 'large scale' references
[1]"Mapping of the Simpson-Golabi-Behmel overgrowth syndrome gene (GPC3) to chromosome X in human and rat by fluorescence in situ hybridization."
Shen T., Sonoda G., Hamid J., Li M., Filmus J., Buick R.N., Testa J.R.
Mamm. Genome 8:72-72(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome."
Pilia G., Hughes-Benzie R.M., Mackenzie A., Baybayan P., Chen E.Y., Huber R., Neri G., Cao A., Forabosco A., Schlessinger D.
Nat. Genet. 12:241-247(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), DISEASE.
Tissue: Embryo.
[3]"Cloning and characterization of human cDNAs encoding a protein with high homology to rat intestinal development protein OCI-5."
Lage H., Dietel M.
Gene 188:151-156(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Expression of the Glypican-3 protein in hepatoma cells."
Grozdanov P.N., Yovchev M.I., Dabeva M.D.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), VARIANT MET-429.
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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."
Huber R., Crisponi L., Mazzarella R., Chen C.N., Su Y., Shizuya H., Chen E.Y., Cao A., Pilia G.
Genomics 45:48-58(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58.
[8]"The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26."
Davoodi J., Kelly J., Gendron N.H., MacKenzie A.E.
Proteomics 7:2300-2310(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DPP4.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Mutational 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."
Veugelers M., Cat B.D., Muyldermans S.Y., Reekmans G., Delande N., Frints S., Legius E., Fryns J.-P., Schrander-Stumpel C., Weidle B., Magdalena N., David G.
Hum. Mol. Genet. 9:1321-1328(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SGBS1 ARG-296.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U50410 mRNA. Translation: AAA93471.1.
L47124 Genomic DNA. Translation: AAA98131.1.
L47125 mRNA. Translation: AAA98132.1.
L47176 mRNA. Translation: AAB58806.1.
Z37987 mRNA. Translation: CAA86069.1.
DQ349136 mRNA. Translation: ABC72125.1.
DQ349138 mRNA. Translation: ABC72127.1.
AL008712 expand/collapse EMBL AC list , AC002420, AF003529, AL009174, Z99570 Genomic DNA. Translation: CAI43110.1.
AL009174 expand/collapse EMBL AC list , AC002420, AF003529, AL008712, Z99570 Genomic DNA. Translation: CAI42761.1.
Z99570 expand/collapse EMBL AC list , AC002420, AF003529, AL008712, AL009174 Genomic DNA. Translation: CAI42277.1.
AL034401 Genomic DNA. No translation available.
AL662851 Genomic DNA. No translation available.
Z97196 Genomic DNA. No translation available.
CH471107 Genomic DNA. Translation: EAX11771.1.
AF003529 Genomic DNA. Translation: AAB87062.1.
CCDSCCDS14638.1. [P51654-1]
CCDS55495.1. [P51654-2]
CCDS55496.1. [P51654-3]
RefSeqNP_001158089.1. NM_001164617.1. [P51654-3]
NP_001158091.1. NM_001164619.1. [P51654-2]
NP_004475.1. NM_004484.3. [P51654-1]
UniGeneHs.644108.

3D structure databases

ProteinModelPortalP51654.
SMRP51654. Positions 34-475.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108983. 2 interactions.
IntActP51654. 1 interaction.
STRING9606.ENSP00000359854.

PTM databases

PhosphoSiteP51654.

Polymorphism databases

DMDM1708022.

Proteomic databases

MaxQBP51654.
PaxDbP51654.
PRIDEP51654.

Protocols and materials databases

DNASU2719.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370818; ENSP00000359854; ENSG00000147257. [P51654-1]
ENST00000394299; ENSP00000377836; ENSG00000147257. [P51654-3]
ENST00000543339; ENSP00000444222; ENSG00000147257. [P51654-2]
GeneID2719.
KEGGhsa:2719.
UCSCuc004exe.2. human. [P51654-1]
uc010nro.2. human.

Organism-specific databases

CTD2719.
GeneCardsGC0XM132669.
GeneReviewsGPC3.
HGNCHGNC:4451. GPC3.
HPACAB017784.
HPA006316.
MIM300037. gene.
312870. phenotype.
neXtProtNX_P51654.
Orphanet373. Simpson-Golabi-Behmel syndrome.
PharmGKBPA28832.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG281821.
HOVERGENHBG005896.
KOK08109.
OMACWNGQEL.
OrthoDBEOG761BTG.
PhylomeDBP51654.
TreeFamTF105317.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
SignaLinkP51654.

Gene expression databases

ArrayExpressP51654.
BgeeP51654.
CleanExHS_GPC3.
GenevestigatorP51654.

Family and domain databases

InterProIPR001863. Glypican.
IPR015501. Glypican-3.
IPR019803. Glypican_CS.
[Graphical view]
PANTHERPTHR10822. PTHR10822. 1 hit.
PTHR10822:SF4. PTHR10822:SF4. 1 hit.
PfamPF01153. Glypican. 1 hit.
[Graphical view]
PROSITEPS01207. GLYPICAN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGPC3. human.
GeneWikiGlypican_3.
GenomeRNAi2719.
NextBio10734.
PROP51654.
SOURCESearch...

Entry information

Entry nameGPC3_HUMAN
AccessionPrimary (citable) accession number: P51654
Secondary accession number(s): C9JLE3 expand/collapse secondary AC list , G3V1R0, Q2L880, Q2L882
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM