UniProtKB - P51654 (GPC3_HUMAN)
Glypican-3
GPC3
Functioni
Miscellaneous
GO - Molecular functioni
- peptidyl-dipeptidase inhibitor activity Source: UniProtKB
GO - Biological processi
- anatomical structure morphogenesis Source: ProtInc
- anterior/posterior axis specification Source: Ensembl
- body morphogenesis Source: Ensembl
- bone mineralization Source: Ensembl
- branching involved in ureteric bud morphogenesis Source: Ensembl
- cell migration Source: GO_Central
- cell migration involved in gastrulation Source: UniProtKB
- cell proliferation involved in kidney development Source: UniProtKB
- cell proliferation involved in metanephros development Source: Ensembl
- cellular protein metabolic process Source: Reactome
- coronary vasculature development Source: UniProtKB
- embryonic hindlimb morphogenesis Source: Ensembl
- glycosaminoglycan biosynthetic process Source: Reactome
- glycosaminoglycan catabolic process Source: Reactome
- lung development Source: Ensembl
- mesenchymal cell proliferation involved in ureteric bud development Source: UniProtKB
- mesonephric duct morphogenesis Source: UniProtKB
- negative regulation of canonical Wnt signaling pathway Source: Ensembl
- negative regulation of epithelial cell proliferation Source: Ensembl
- negative regulation of growth Source: Ensembl
- negative regulation of smoothened signaling pathway Source: UniProtKB
- osteoclast differentiation Source: Ensembl
- positive regulation of BMP signaling pathway Source: Ensembl
- positive regulation of canonical Wnt signaling pathway Source: UniProtKB
- positive regulation of endocytosis Source: UniProtKB
- positive regulation of glucose import Source: Ensembl
- positive regulation of protein catabolic process Source: UniProtKB
- positive regulation of smoothened signaling pathway Source: Ensembl
- positive regulation of Wnt signaling pathway, planar cell polarity pathway Source: Ensembl
- post-translational protein modification Source: Reactome
- regulation of canonical Wnt signaling pathway Source: UniProtKB
- regulation of non-canonical Wnt signaling pathway Source: UniProtKB
- regulation of protein localization to membrane Source: GO_Central
- response to bacterium Source: Ensembl
- retinoid metabolic process Source: Reactome
Keywordsi
Molecular function | Protease inhibitor |
Enzyme and pathway databases
PathwayCommonsi | P51654 |
Reactomei | R-HSA-1971475, A tetrasaccharide linker sequence is required for GAG synthesis R-HSA-2022928, HS-GAG biosynthesis R-HSA-2024096, HS-GAG degradation R-HSA-3560783, Defective B4GALT7 causes EDS, progeroid type R-HSA-3560801, Defective B3GAT3 causes JDSSDHD R-HSA-3656237, Defective EXT2 causes exostoses 2 R-HSA-3656253, Defective EXT1 causes exostoses 1, TRPS2 and CHDS R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-4420332, Defective B3GALT6 causes EDSP2 and SEMDJL1 R-HSA-8957275, Post-translational protein phosphorylation R-HSA-975634, Retinoid metabolism and transport |
SignaLinki | P51654 |
SIGNORi | P51654 |
Names & Taxonomyi
Protein namesi | Recommended name: Glypican-3Alternative name(s): GTR2-2 Intestinal protein OCI-5 MXR7 Cleaved into the following 2 chains: Glypican-3 alpha subunit1 Publication Glypican-3 beta subunit1 Publication |
Gene namesi | Name:GPC3 Synonyms:OCI5 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4451, GPC3 |
MIMi | 300037, gene |
neXtProti | NX_P51654 |
VEuPathDBi | HostDB:ENSG00000147257.13 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; GPI-anchor By similarity; Extracellular side By similarity
Endoplasmic reticulum
- endoplasmic reticulum lumen Source: Reactome
Extracellular region or secreted
- collagen-containing extracellular matrix Source: InterPro
- extracellular region Source: GO_Central
Golgi apparatus
- Golgi lumen Source: Reactome
Lysosome
- lysosomal lumen Source: Reactome
Plasma Membrane
- anchored component of plasma membrane Source: UniProtKB
- intrinsic component of plasma membrane Source: UniProtKB
- plasma membrane Source: HPA
Other locations
- cell surface Source: GO_Central
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Simpson-Golabi-Behmel syndrome 1 (SGBS1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021385 | 296 | W → R in SGBS1. 1 PublicationCorresponds to variant dbSNP:rs104894854EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 355 – 358 | RQYR → AQYA: Abolishes proteolytic processing. Abolishes interaction with WNT5A and ability to regulate Wnt signaling. Increases binding of hedgehog protein SHH to the PTC1 receptor and abolishes ability to inhibit hedgehog signaling. 3 Publications | 4 | |
Mutagenesisi | 355 | R → A: No effect on proteolytic processing. 1 Publication | 1 | |
Mutagenesisi | 358 | R → A: No effect on proteolytic processing. 1 Publication | 1 | |
Mutagenesisi | 371 – 374 | KVLK → AVLA: No effect on proteolytic processing. 1 Publication | 4 | |
Mutagenesisi | 387 – 389 | RRR → AAA: No effect on proteolytic processing. 1 Publication | 3 | |
Mutagenesisi | 394 – 396 | KLK → ALA: No effect on proteolytic processing. 1 Publication | 3 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 2719 |
GeneReviewsi | GPC3 |
MalaCardsi | GPC3 |
MIMi | 312870, phenotype |
OpenTargetsi | ENSG00000147257 |
Orphaneti | 654, Nephroblastoma 373, Simpson-Golabi-Behmel syndrome |
PharmGKBi | PA28832 |
Miscellaneous databases
Pharosi | P51654, Tbio |
Genetic variation databases
BioMutai | GPC3 |
DMDMi | 1708022 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | 1 PublicationAdd BLAST | 24 | |
ChainiPRO_0000445410 | 25 – 358 | Glypican-3 alpha subunit1 PublicationAdd BLAST | 334 | |
ChainiPRO_0000445411 | 359 – 554 | Glypican-3 beta subunit1 PublicationAdd BLAST | 196 | |
PropeptideiPRO_0000012310 | 555 – 580 | Removed in mature formSequence analysisAdd BLAST | 26 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 25 | Pyrrolidone carboxylic acid1 Publication | 1 | |
Disulfide bondi | 35 ↔ 72 | By similarity | ||
Disulfide bondi | 65 ↔ 262 | By similarity | ||
Disulfide bondi | 73 ↔ 265 | By similarity | ||
Glycosylationi | 124 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 197 ↔ 349 | By similarity | ||
Glycosylationi | 241 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 252 ↔ 285 | By similarity | ||
Disulfide bondi | 274 ↔ 422 | Interchain (between alpha and beta chains)By similarity | ||
Disulfide bondi | 278 ↔ 410 | Interchain (between alpha and beta chains)By similarity | ||
Modified residuei | 352 | Phosphoserine; by FAM20C1 Publication | 1 | |
Glycosylationi | 418 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 495 | O-linked (Xyl...) (heparan sulfate) serineSequence analysis | 1 | |
Glycosylationi | 509 | O-linked (Xyl...) (heparan sulfate) serineSequence analysis | 1 | |
Lipidationi | 554 | GPI-anchor amidated asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 358 – 359 | Cleavage2 Publications | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, Heparan sulfate, Lipoprotein, Phosphoprotein, Proteoglycan, Pyrrolidone carboxylic acidProteomic databases
EPDi | P51654 |
jPOSTi | P51654 |
MassIVEi | P51654 |
MaxQBi | P51654 |
PaxDbi | P51654 |
PeptideAtlasi | P51654 |
PRIDEi | P51654 |
ProteomicsDBi | 10697 32411 56359 [P51654-1] |
TopDownProteomicsi | P51654-1 [P51654-1] |
PTM databases
GlyGeni | P51654, 5 sites |
iPTMneti | P51654 |
PhosphoSitePlusi | P51654 |
SwissPalmi | P51654 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000147257, Expressed in kidney and 187 other tissues |
ExpressionAtlasi | P51654, baseline and differential |
Genevisiblei | P51654, HS |
Organism-specific databases
HPAi | ENSG00000147257, Tissue enriched (placenta) |
Interactioni
Subunit structurei
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).
By similarity4 PublicationsProtein-protein interaction databases
BioGRIDi | 108983, 30 interactors |
DIPi | DIP-61509N |
IntActi | P51654, 22 interactors |
STRINGi | 9606.ENSP00000377836 |
Miscellaneous databases
RNActi | P51654, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3821, Eukaryota |
GeneTreei | ENSGT00990000203655 |
HOGENOMi | CLU_024658_4_2_1 |
InParanoidi | P51654 |
OMAi | VHAQKNE |
PhylomeDBi | P51654 |
TreeFami | TF105317 |
Family and domain databases
InterProi | View protein in InterPro IPR001863, Glypican IPR015501, Glypican-3 IPR019803, Glypican_CS |
PANTHERi | PTHR10822, PTHR10822, 1 hit PTHR10822:SF4, PTHR10822:SF4, 1 hit |
Pfami | View protein in Pfam PF01153, Glypican, 1 hit |
PROSITEi | View protein in PROSITE PS01207, GLYPICAN, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAGTVRTACL VVAMLLSLDF PGQAQPPPPP PDATCHQVRS FFQRLQPGLK
60 70 80 90 100
WVPETPVPGS DLQVCLPKGP TCCSRKMEEK YQLTARLNME QLLQSASMEL
110 120 130 140 150
KFLIIQNAAV FQEAFEIVVR HAKNYTNAMF KNNYPSLTPQ AFEFVGEFFT
160 170 180 190 200
DVSLYILGSD INVDDMVNEL FDSLFPVIYT QLMNPGLPDS ALDINECLRG
210 220 230 240 250
ARRDLKVFGN FPKLIMTQVS KSLQVTRIFL QALNLGIEVI NTTDHLKFSK
260 270 280 290 300
DCGRMLTRMW YCSYCQGLMM VKPCGGYCNV VMQGCMAGVV EIDKYWREYI
310 320 330 340 350
LSLEELVNGM YRIYDMENVL LGLFSTIHDS IQYVQKNAGK LTTTIGKLCA
360 370 380 390 400
HSQQRQYRSA YYPEDLFIDK KVLKVAHVEH EETLSSRRRE LIQKLKSFIS
410 420 430 440 450
FYSALPGYIC SHSPVAENDT LCWNGQELVE RYSQKAARNG MKNQFNLHEL
460 470 480 490 500
KMKGPEPVVS QIIDKLKHIN QLLRTMSMPK GRVLDKNLDE EGFESGDCGD
510 520 530 540 550
DEDECIGGSG DGMIKVKNQL RFLAELAYDL DVDDAPGNSQ QATPKDNEIS
560 570 580
TFHNLGNVHS PLKLLTSMAI SVVCFFFLVH
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0Y3U6 | H0Y3U6_HUMAN | Glypican-3 | GPC3 | 256 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021385 | 296 | W → R in SGBS1. 1 PublicationCorresponds to variant dbSNP:rs104894854EnsemblClinVar. | 1 | |
Natural variantiVAR_069139 | 429 | V → M1 PublicationCorresponds to variant dbSNP:rs11539789Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_046117 | 59 – 112 | Missing in isoform 2. 1 PublicationAdd BLAST | 54 | |
Alternative sequenceiVSP_046703 | 344 | T → TETEKKIWHFKYPIFFLCIG LDLQ in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 , 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 |
CCDSi | CCDS14638.1 [P51654-1] CCDS55495.1 [P51654-2] CCDS55496.1 [P51654-3] |
RefSeqi | NP_001158089.1, NM_001164617.1 [P51654-3] NP_001158091.1, NM_001164619.1 [P51654-2] NP_004475.1, NM_004484.3 [P51654-1] |
Genome annotation databases
Ensembli | ENST00000370818; ENSP00000359854; ENSG00000147257 [P51654-1] ENST00000394299; ENSP00000377836; ENSG00000147257 [P51654-3] ENST00000631057; ENSP00000486325; ENSG00000147257 [P51654-2] |
GeneIDi | 2719 |
KEGGi | hsa:2719 |
UCSCi | uc004exe.4, human [P51654-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 , 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 |
CCDSi | CCDS14638.1 [P51654-1] CCDS55495.1 [P51654-2] CCDS55496.1 [P51654-3] |
RefSeqi | NP_001158089.1, NM_001164617.1 [P51654-3] NP_001158091.1, NM_001164619.1 [P51654-2] NP_004475.1, NM_004484.3 [P51654-1] |
3D structure databases
SMRi | P51654 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108983, 30 interactors |
DIPi | DIP-61509N |
IntActi | P51654, 22 interactors |
STRINGi | 9606.ENSP00000377836 |
PTM databases
GlyGeni | P51654, 5 sites |
iPTMneti | P51654 |
PhosphoSitePlusi | P51654 |
SwissPalmi | P51654 |
Genetic variation databases
BioMutai | GPC3 |
DMDMi | 1708022 |
Proteomic databases
EPDi | P51654 |
jPOSTi | P51654 |
MassIVEi | P51654 |
MaxQBi | P51654 |
PaxDbi | P51654 |
PeptideAtlasi | P51654 |
PRIDEi | P51654 |
ProteomicsDBi | 10697 32411 56359 [P51654-1] |
TopDownProteomicsi | P51654-1 [P51654-1] |
Protocols and materials databases
ABCDi | P51654, 43 sequenced antibodies |
Antibodypediai | 424, 1384 antibodies |
DNASUi | 2719 |
Genome annotation databases
Ensembli | ENST00000370818; ENSP00000359854; ENSG00000147257 [P51654-1] ENST00000394299; ENSP00000377836; ENSG00000147257 [P51654-3] ENST00000631057; ENSP00000486325; ENSG00000147257 [P51654-2] |
GeneIDi | 2719 |
KEGGi | hsa:2719 |
UCSCi | uc004exe.4, human [P51654-1] |
Organism-specific databases
CTDi | 2719 |
DisGeNETi | 2719 |
GeneCardsi | GPC3 |
GeneReviewsi | GPC3 |
HGNCi | HGNC:4451, GPC3 |
HPAi | ENSG00000147257, Tissue enriched (placenta) |
MalaCardsi | GPC3 |
MIMi | 300037, gene 312870, phenotype |
neXtProti | NX_P51654 |
OpenTargetsi | ENSG00000147257 |
Orphaneti | 654, Nephroblastoma 373, Simpson-Golabi-Behmel syndrome |
PharmGKBi | PA28832 |
VEuPathDBi | HostDB:ENSG00000147257.13 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3821, Eukaryota |
GeneTreei | ENSGT00990000203655 |
HOGENOMi | CLU_024658_4_2_1 |
InParanoidi | P51654 |
OMAi | VHAQKNE |
PhylomeDBi | P51654 |
TreeFami | TF105317 |
Enzyme and pathway databases
PathwayCommonsi | P51654 |
Reactomei | R-HSA-1971475, A tetrasaccharide linker sequence is required for GAG synthesis R-HSA-2022928, HS-GAG biosynthesis R-HSA-2024096, HS-GAG degradation R-HSA-3560783, Defective B4GALT7 causes EDS, progeroid type R-HSA-3560801, Defective B3GAT3 causes JDSSDHD R-HSA-3656237, Defective EXT2 causes exostoses 2 R-HSA-3656253, Defective EXT1 causes exostoses 1, TRPS2 and CHDS R-HSA-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-4420332, Defective B3GALT6 causes EDSP2 and SEMDJL1 R-HSA-8957275, Post-translational protein phosphorylation R-HSA-975634, Retinoid metabolism and transport |
SignaLinki | P51654 |
SIGNORi | P51654 |
Miscellaneous databases
BioGRID-ORCSi | 2719, 2 hits in 501 CRISPR screens |
ChiTaRSi | GPC3, human |
GeneWikii | Glypican_3 |
GenomeRNAii | 2719 |
Pharosi | P51654, Tbio |
PROi | PR:P51654 |
RNActi | P51654, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000147257, Expressed in kidney and 187 other tissues |
ExpressionAtlasi | P51654, baseline and differential |
Genevisiblei | P51654, HS |
Family and domain databases
InterProi | View protein in InterPro IPR001863, Glypican IPR015501, Glypican-3 IPR019803, Glypican_CS |
PANTHERi | PTHR10822, PTHR10822, 1 hit PTHR10822:SF4, PTHR10822:SF4, 1 hit |
Pfami | View protein in Pfam PF01153, Glypican, 1 hit |
PROSITEi | View protein in PROSITE PS01207, GLYPICAN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GPC3_HUMAN | |
Accessioni | P51654Primary (citable) accession number: P51654 Secondary accession number(s): C9JLE3 Q2L882 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | February 10, 2021 | |
This is version 191 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families