P51654 (GPC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	580 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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-anchor › GPI-anchor; Extracellular side By similarity. Secreted glypican-3: Secreted › extracellular 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 component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal
Molecular function	Protease inhibitor
PTM	GPI-anchor Glycoprotein Heparan sulfate Lipoprotein Proteoglycan
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anatomical structure morphogenesis Traceable author statement Ref.2. Source: ProtInc carbohydrate metabolic process Traceable author statement. Source: Reactome chondroitin sulfate metabolic process Traceable author statement. Source: Reactome glycosaminoglycan biosynthetic process Traceable author statement. Source: Reactome glycosaminoglycan catabolic process Traceable author statement. Source: Reactome mesenchymal cell proliferation involved in ureteric bud development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 7657705. Source: ProtInc lysosomal lumen Traceable author statement. Source: Reactome proteinaceous extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular_function	peptidyl-dipeptidase inhibitor activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 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)

The sequence of this isoform differs from the canonical sequence as follows:
     59-112: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Chain	25 – ?		Glypican-3		PRO_0000012309
	Chain	25 – ?		Secreted glypican-3		PRO_0000333844
	Propeptide	? – 580		Removed in mature form Potential		PRO_0000012310
Amino acid modifications
	Glycosylation	124	1	N-linked (GlcNAc...) Potential
	Glycosylation	241	1	N-linked (GlcNAc...) Potential
	Glycosylation	418	1	N-linked (GlcNAc...) Potential
	Glycosylation	495	1	O-linked (Xyl...) (heparan sulfate) Potential
	Glycosylation	509	1	O-linked (Xyl...) (heparan sulfate) Potential
Natural variations
	Alternative sequence	59 – 112	54	Missing in isoform 2.		VSP_046117
	Natural variant	296	1	W → R in SGBS1. Ref.10		VAR_021385
	Natural variant	429	1	V → M. Ref.4 Corresponds to variant rs413112608 [ dbSNP | Ensembl ].		VAR_069139

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 19485B76D3CE15FC	FASTA	580	65,563
	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
	Isoform 2 [UniParc]. Checksum: A0858770AF739C17	FASTA	526	59,475
	10 20 30 40 50 60 MAGTVRTACL VVAMLLSLDF PGQAQPPPPP PDATCHQVRS FFQRLQPGLK WVPETPVPEA 70 80 90 100 110 120 FEIVVRHAKN YTNAMFKNNY PSLTPQAFEF VGEFFTDVSL YILGSDINVD DMVNELFDSL 130 140 150 160 170 180 FPVIYTQLMN PGLPDSALDI NECLRGARRD LKVFGNFPKL IMTQVSKSLQ VTRIFLQALN 190 200 210 220 230 240 LGIEVINTTD HLKFSKDCGR MLTRMWYCSY CQGLMMVKPC GGYCNVVMQG CMAGVVEIDK 250 260 270 280 290 300 YWREYILSLE ELVNGMYRIY DMENVLLGLF STIHDSIQYV QKNAGKLTTT IGKLCAHSQQ 310 320 330 340 350 360 RQYRSAYYPE DLFIDKKVLK VAHVEHEETL SSRRRELIQK LKSFISFYSA LPGYICSHSP 370 380 390 400 410 420 VAENDTLCWN GQELVERYSQ KAARNGMKNQ FNLHELKMKG PEPVVSQIID KLKHINQLLR 430 440 450 460 470 480 TMSMPKGRVL DKNLDEEGFE SGDCGDDEDE CIGGSGDGMI KVKNQLRFLA ELAYDLDVDD 490 500 510 520 APGNSQQATP KDNEISTFHN LGNVHSPLKL LTSMAISVVC FFFLVH

References

	« Hide 'large scale' referencesShow '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] (ISOFORM 2), 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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

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. AL008712 , AC002420, AF003529, AL009174, Z99570 Genomic DNA. Translation: CAI43110.1. AL009174 , AC002420, AF003529, AL008712, Z99570 Genomic DNA. Translation: CAI42761.1. Z99570 , 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.
IPI	IPI00019907. IPI00646987.
RefSeq	NP_001158091.1. NM_001164619.1. NP_004475.1. NM_004484.3.
UniGene	Hs.644108.
3D structure databases
ProteinModelPortal	P51654.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51654. 1 interaction.
STRING	9606.ENSP00000359854.
PTM databases
PhosphoSite	P51654.
Polymorphism databases
DMDM	1708022.
Proteomic databases
PaxDb	P51654.
PRIDE	P51654.
Protocols and materials databases
DNASU	2719.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370818; ENSP00000359854; ENSG00000147257. ENST00000543339; ENSP00000444222; ENSG00000147257.
GeneID	2719.
KEGG	hsa:2719.
UCSC	uc004exe.2. human.
Organism-specific databases
CTD	2719.
GeneCards	GC0XM132669.
HGNC	HGNC:4451. GPC3.
HPA	CAB017784. HPA006316.
MIM	300037. gene. 312870. phenotype.
neXtProt	NX_P51654.
Orphanet	654. Nephroblastoma. 373. Simpson-Golabi-Behmel syndrome.
PharmGKB	PA28832.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG281821.
HOVERGEN	HBG005896.
KO	K08109.
OrthoDB	EOG44J2HP.
PhylomeDB	P51654.
Enzyme and pathway databases
Pathway_Interaction_DB	glypican_3pathway. Glypican 3 network. glypicanpathway. Glypican pathway.
Reactome	REACT_111217. Metabolism. REACT_116125. Disease.
Gene expression databases
ArrayExpress	P51654.
Bgee	P51654.
CleanEx	HS_GPC3.
Genevestigator	P51654.
GermOnline	ENSG00000147257. Homo sapiens.
Family and domain databases
InterPro	IPR001863. Glypican. IPR015501. Glypican-3. IPR019803. Glypican_CS. [Graphical view]
PANTHER	PTHR10822. PTHR10822. 1 hit. PTHR10822:SF4. PTHR10822:SF4. 1 hit.
Pfam	PF01153. Glypican. 1 hit. [Graphical view]
PROSITE	PS01207. GLYPICAN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GPC3. human.
GenomeRNAi	2719.
NextBio	10734.
SOURCE	Search...

Entry information

Entry name

GPC3_HUMAN

Accession

Primary (citable) accession number: P51654
Secondary accession number(s): G3V1R0, Q2L882

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.