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UniProtKB - P51654 (GPC3_HUMAN)

Entry version 191 (10 Feb 2021)
Sequence version 1 (01 Oct 1996)
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Protein

Glypican-3

Gene

GPC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Cell surface proteoglycan that bears heparan sulfate (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).By similarity4 Publications

Miscellaneous

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).3 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionProtease inhibitor

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P51654

Reactome - a knowledgebase of biological pathways and processes

More...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

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P51654

SIGNOR Signaling Network Open Resource

More...SIGNORi		P51654

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Glypican-3
Alternative 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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:GPC3
Synonyms:OCI5
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome X

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:4451, GPC3

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		300037, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P51654

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000147257.13

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Simpson-Golabi-Behmel syndrome 1 (SGBS1)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_021385296W → R in SGBS1. 1 PublicationCorresponds to variant dbSNP:rs104894854EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi355 – 358RQYR → 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 Publications4
Mutagenesisi355R → A: No effect on proteolytic processing. 1 Publication1
Mutagenesisi358R → A: No effect on proteolytic processing. 1 Publication1
Mutagenesisi371 – 374KVLK → AVLA: No effect on proteolytic processing. 1 Publication4
Mutagenesisi387 – 389RRR → AAA: No effect on proteolytic processing. 1 Publication3
Mutagenesisi394 – 396KLK → ALA: No effect on proteolytic processing. 1 Publication3

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		2719

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		GPC3

MalaCards human disease database

More...MalaCardsi		GPC3
MIMi312870, phenotype

Open Targets

More...OpenTargetsi		ENSG00000147257

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		654, Nephroblastoma
373, Simpson-Golabi-Behmel syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA28832

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P51654, Tbio

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		GPC3

Domain mapping of disease mutations (DMDM)

More...DMDMi		1708022

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 241 PublicationAdd BLAST24
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000044541025 – 358Glypican-3 alpha subunit1 PublicationAdd BLAST334
ChainiPRO_0000445411359 – 554Glypican-3 beta subunit1 PublicationAdd BLAST196
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_0000012310555 – 580Removed in mature formSequence analysisAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei25Pyrrolidone carboxylic acid1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi35 ↔ 72By similarity
Disulfide bondi65 ↔ 262By similarity
Disulfide bondi73 ↔ 265By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi124N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi197 ↔ 349By similarity
Glycosylationi241N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi252 ↔ 285By similarity
Disulfide bondi274 ↔ 422Interchain (between alpha and beta chains)By similarity
Disulfide bondi278 ↔ 410Interchain (between alpha and beta chains)By similarity
Modified residuei352Phosphoserine; by FAM20C1 Publication1
Glycosylationi418N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi495O-linked (Xyl...) (heparan sulfate) serineSequence analysis1
Glycosylationi509O-linked (Xyl...) (heparan sulfate) serineSequence analysis1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi554GPI-anchor amidated asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

O-glycosylated; contains heparan sulfate.1 Publication
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).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei358 – 359Cleavage2 Publications2

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Heparan sulfate, Lipoprotein, Phosphoprotein, Proteoglycan, Pyrrolidone carboxylic acid

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P51654

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P51654

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P51654

MaxQB - The MaxQuant DataBase

More...MaxQBi		P51654

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P51654

PeptideAtlas

More...PeptideAtlasi		P51654

PRoteomics IDEntifications database

More...PRIDEi		P51654

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		10697
32411
56359 [P51654-1]

Consortium for Top Down Proteomics

More...TopDownProteomicsi		P51654-1 [P51654-1]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P51654, 5 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P51654

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P51654

SwissPalm database of S-palmitoylation events

More...SwissPalmi		P51654

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in lung, liver and kidney.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000147257, Expressed in kidney and 187 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P51654, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P51654, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000147257, Tissue enriched (placenta)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 Publications

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		108983, 30 interactors

Database of interacting proteins

More...DIPi		DIP-61509N

Protein interaction database and analysis system

More...IntActi		P51654, 22 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000377836

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P51654, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P51654

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the glypican family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3821, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00990000203655

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_024658_4_2_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P51654

Identification of Orthologs from Complete Genome Data

More...OMAi		VHAQKNE

Database for complete collections of gene phylogenies

More...PhylomeDBi		P51654

TreeFam database of animal gene trees

More...TreeFami		TF105317

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR001863, Glypican
IPR015501, Glypican-3
IPR019803, Glypican_CS

The PANTHER Classification System

More...PANTHERi		PTHR10822, PTHR10822, 1 hit
PTHR10822:SF4, PTHR10822:SF4, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF01153, Glypican, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS01207, GLYPICAN, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P51654-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:580
Mass (Da):65,563
Last modified:October 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i19485B76D3CE15FC
GO
Isoform 2 (identifier: P51654-2) [UniParc]FASTAAdd to basket
Also known as: Variant B

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

Show »
Length:526
Mass (Da):59,475
Checksum:iA0858770AF739C17
GO
Isoform 3 (identifier: P51654-3) [UniParc]FASTAAdd to basket
Also known as: Variant C

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

Show »
Length:603
Mass (Da):68,414
Checksum:i1930C0382E91AF60
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y3U6H0Y3U6_HUMAN
Glypican-3
GPC3
256Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021385296W → R in SGBS1. 1 PublicationCorresponds to variant dbSNP:rs104894854EnsemblClinVar.1
Natural variantiVAR_069139429V → M1 PublicationCorresponds to variant dbSNP:rs11539789Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_04611759 – 112Missing in isoform 2. 1 PublicationAdd BLAST54
Alternative sequenceiVSP_046703344T → TETEKKIWHFKYPIFFLCIG LDLQ in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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 Z99570 Genomic DNA Translation: CAI43110.1
AL009174 Z99570 Genomic DNA Translation: CAI42761.1
Z99570 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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS14638.1 [P51654-1]
CCDS55495.1 [P51654-2]
CCDS55496.1 [P51654-3]

NCBI Reference Sequences

More...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

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000370818; ENSP00000359854; ENSG00000147257 [P51654-1]
ENST00000394299; ENSP00000377836; ENSG00000147257 [P51654-3]
ENST00000631057; ENSP00000486325; ENSG00000147257 [P51654-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		2719

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:2719

UCSC genome browser

More...UCSCi		uc004exe.4, human [P51654-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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 Z99570 Genomic DNA Translation: CAI43110.1
AL009174 Z99570 Genomic DNA Translation: CAI42761.1
Z99570 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
CCDSiCCDS14638.1 [P51654-1]
CCDS55495.1 [P51654-2]
CCDS55496.1 [P51654-3]
RefSeqiNP_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

SMRiP51654
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi108983, 30 interactors
DIPiDIP-61509N
IntActiP51654, 22 interactors
STRINGi9606.ENSP00000377836

PTM databases

GlyGeniP51654, 5 sites
iPTMnetiP51654
PhosphoSitePlusiP51654
SwissPalmiP51654

Genetic variation databases

BioMutaiGPC3
DMDMi1708022

Proteomic databases

EPDiP51654
jPOSTiP51654
MassIVEiP51654
MaxQBiP51654
PaxDbiP51654
PeptideAtlasiP51654
PRIDEiP51654
ProteomicsDBi10697
32411
56359 [P51654-1]
TopDownProteomicsiP51654-1 [P51654-1]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		P51654, 43 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		424, 1384 antibodies

The DNASU plasmid repository

More...DNASUi		2719

Genome annotation databases

EnsembliENST00000370818; ENSP00000359854; ENSG00000147257 [P51654-1]
ENST00000394299; ENSP00000377836; ENSG00000147257 [P51654-3]
ENST00000631057; ENSP00000486325; ENSG00000147257 [P51654-2]
GeneIDi2719
KEGGihsa:2719
UCSCiuc004exe.4, human [P51654-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		2719
DisGeNETi2719

GeneCards: human genes, protein and diseases

More...GeneCardsi		GPC3
GeneReviewsiGPC3
HGNCiHGNC:4451, GPC3
HPAiENSG00000147257, Tissue enriched (placenta)
MalaCardsiGPC3
MIMi300037, gene
312870, phenotype
neXtProtiNX_P51654
OpenTargetsiENSG00000147257
Orphaneti654, Nephroblastoma
373, Simpson-Golabi-Behmel syndrome
PharmGKBiPA28832
VEuPathDBiHostDB:ENSG00000147257.13

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG3821, Eukaryota
GeneTreeiENSGT00990000203655
HOGENOMiCLU_024658_4_2_1
InParanoidiP51654
OMAiVHAQKNE
PhylomeDBiP51654
TreeFamiTF105317

Enzyme and pathway databases

PathwayCommonsiP51654
ReactomeiR-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
SignaLinkiP51654
SIGNORiP51654

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		2719, 2 hits in 501 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		GPC3, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Glypican_3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		2719
PharosiP51654, Tbio

Protein Ontology

More...PROi		PR:P51654
RNActiP51654, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000147257, Expressed in kidney and 187 other tissues
ExpressionAtlasiP51654, baseline and differential
GenevisibleiP51654, HS

Family and domain databases

InterProiView protein in InterPro
IPR001863, Glypican
IPR015501, Glypican-3
IPR019803, Glypican_CS
PANTHERiPTHR10822, PTHR10822, 1 hit
PTHR10822:SF4, PTHR10822:SF4, 1 hit
PfamiView protein in Pfam
PF01153, Glypican, 1 hit
PROSITEiView protein in PROSITE
PS01207, GLYPICAN, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiGPC3_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P51654
Secondary accession number(s): C9JLE3
, G3V1R0, Q2L880, Q2L882
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated 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.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
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