Q8CFZ4 · GPC3_MOUSE

  • Protein
    Glypican-3
  • Gene
    Gpc3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Cell surface proteoglycan (By similarity).
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 (PubMed:18477453, PubMed:23665349).
Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (PubMed:18477453).
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 (By similarity).
Positively regulates the non-canonical Wnt signaling pathway (PubMed:15537637).
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 (PubMed:23665349).
Inhibits the dipeptidyl peptidase activity of DPP4 (By similarity).
Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (PubMed:10964473).
Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (PubMed:11180950).
Required for coronary vascular development (PubMed:19733558).
Plays a role in regulating cell movements during gastrulation (By similarity).

GO annotations

AspectTerm
Cellular Componentcell surface
Cellular Componentcollagen-containing extracellular matrix
Cellular ComponentGolgi lumen
Cellular Componentlysosome
Cellular Componentplasma membrane
Cellular Componentside of membrane
Molecular Functionpeptidyl-dipeptidase inhibitor activity
Biological Processanimal organ morphogenesis
Biological Processanterior/posterior axis specification
Biological Processbody morphogenesis
Biological Processbone mineralization
Biological Processbranching involved in ureteric bud morphogenesis
Biological Processcanonical Wnt signaling pathway
Biological Processcell migration
Biological Processcell migration involved in gastrulation
Biological Processcell proliferation involved in kidney development
Biological Processcell proliferation involved in metanephros development
Biological Processcoronary vasculature development
Biological Processembryonic hindlimb morphogenesis
Biological Processepithelial cell proliferation
Biological Processkidney development
Biological Processlung development
Biological Processmesenchymal cell proliferation involved in ureteric bud development
Biological Processmesonephric duct morphogenesis
Biological Processnegative regulation of canonical Wnt signaling pathway
Biological Processnegative regulation of cell population proliferation
Biological Processnegative regulation of epithelial cell proliferation
Biological Processnegative regulation of growth
Biological Processnegative regulation of smoothened signaling pathway
Biological Processosteoclast differentiation
Biological Processpositive regulation of BMP signaling pathway
Biological Processpositive regulation of canonical Wnt signaling pathway
Biological Processpositive regulation of endocytosis
Biological Processpositive regulation of glucose import
Biological Processpositive regulation of protein catabolic process
Biological Processpositive regulation of smoothened signaling pathway
Biological Processpositive regulation of Wnt signaling pathway, planar cell polarity pathway
Biological Processregulation of canonical Wnt signaling pathway
Biological Processregulation of growth
Biological Processregulation of non-canonical Wnt signaling pathway
Biological Processregulation of protein localization to membrane
Biological Processresponse to bacterium
Biological Processsmoothened signaling pathway
Biological ProcessWnt signaling pathway, planar cell polarity pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      Gpc3

Organism names

  • Taxonomic identifier
  • Strain
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8CFZ4

Proteomes

Organism-specific databases

Subcellular Location

Phenotypes & Variants

Disruption phenotype

Perinatal death, developmental overgrowth, cystic and dyplastic kidneys, abnormal lung development and ventral wall closure defects (PubMed:10402475, PubMed:10964473).
A proportion of mutants also display mandibular hypoplasia and an imperforate vagina (PubMed:10402475).
There is an early and persistent abnormality in ureteric bud development in the kidney due to increased cell proliferation (PubMed:10402475).
In the developing kidney, cell proliferation is increased threefold in cortical collecting duct cells and apoptosis is increased 16-fold in medullary collecting duct cells (PubMed:11180950).
High incidence of congenital cardiac malformations including ventricular septal defects, common atrioventricular canal, double outlet right ventricle and presence of coronary artery fistulas (PubMed:19733558).
Elevated levels of hedgehog pathway proteins Gli1 and Ptc1, indicative of activation of the hedgehog pathway and increased levels of Shh (PubMed:18477453).
Reduced non-canonical Wnt signaling (PubMed:15537637).
Similar levels of tissue and serum Igf2 to wild-type mice (PubMed:10402475).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 36 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, modified residue, chain, disulfide bond, glycosylation, lipidation, propeptide.

TypeIDPosition(s)Description
Signal1-24
Modified residue25Pyrrolidone carboxylic acid
ChainPRO_000044541225-357Glypican-3 alpha subunit
Disulfide bond34↔71
Disulfide bond64↔261
Disulfide bond72↔264
Glycosylation123N-linked (GlcNAc...) asparagine
Disulfide bond196↔348
Glycosylation240N-linked (GlcNAc...) asparagine
Disulfide bond251↔284
Disulfide bond273↔421Interchain (between alpha and beta chains)
Disulfide bond277↔409Interchain (between alpha and beta chains)
Modified residue351Phosphoserine
ChainPRO_0000445413358-553Glypican-3 beta subunit
Glycosylation417N-linked (GlcNAc...) asparagine
Glycosylation494O-linked (Xyl...) (glycosaminoglycan) serine
Glycosylation508O-linked (Xyl...) (glycosaminoglycan) serine
Lipidation553GPI-anchor amidated serine
PropeptidePRO_0000012312554-579Removed in mature form

Post-translational modification

O-glycosylated; contains heparan sulfate and/or chondroitin sulfate.
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. This processing is essential for its role in inhibition of hedgehog signaling. 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.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

In the developing limb, absent from the apical epidermal ridge at 11 dpc but highly expressed in the underlying mesenchyme (PubMed:10964473).
Expression in the mesenchyme at this stage is asymmetric with highest levels in the regions of the distal mesenchyme within the progress zone and within the proximal anterior and posterior limb bud (PubMed:10964473).
At later developmental stages including 12.5 and 13.5 dpc, expression is restricted to the interdigital webs and the regions of chondrocytic differentiation of the developing bones (PubMed:10964473).
In the embryonic kidney, expressed in both the ureteric bud and mesenchymal cells as early as 13.5 dpc (PubMed:11180950).
Expression at 16.5 dpc is similar to that at 13.5 dpc but decreases by 18.5 dpc (PubMed:11180950).

Gene expression databases

Interaction

Subunit

Heterodimer; disulfide-linked (By similarity).
Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer (By similarity).
Interacts with DPP4 (By similarity).
Interacts with FGF2 (By similarity).
Interacts with WNT5A (By similarity).
Also interacts with WNT3A and WNT7B (By similarity).
Interacts with hedgehog protein SHH; the heparan sulfate chains are not required for the interaction (PubMed:18477453).
Also interacts with hedgehog protein IHH (PubMed:23665349).
Interacts with CD81 (PubMed:23665349).
Interacts with Wnt receptors FZD4, FZD7 and FZD8; the heparan sulfate chains are required for the interaction (By similarity).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region533-552Disordered

Sequence similarities

Belongs to the glypican family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    579
  • Mass (Da)
    65,332
  • Last updated
    2003-03-01 v1
  • Checksum
    066C23B3493A9346
MAGTVRTACLLVAMLLGLGCLGQAQPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQMMNPGLPESVLDINECLRGARRDLKVFGSFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNGGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKILKVAHVEHEETLSSRRRELIQKLKSFINFYSALPGYICSHSPVAENDTLCWNGQELVERYSQKAARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSVPKGKVLDKSLDEEGLESGDCGDDEDECIGSSGDGMVKVKNQLRFLAELAYDLDVDDAPGNKQHGNQKDNEITTSHSVGNMPSPLKILISVAIYVACFFFLVH

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
B1ATR5B1ATR5_MOUSEGpc3430

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
BC036126
EMBL· GenBank· DDBJ
AAH36126.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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