Q8CFZ4 · GPC3_MOUSE
- ProteinGlypican-3
- GeneGpc3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids579 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlypican-3
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CFZ4
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).
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.
PTM/Processing
Features
Showing features for signal, modified residue, chain, disulfide bond, glycosylation, lipidation, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MAGTVRTACLLVAMLLGLGCLGQA | ||||||
Modified residue | 25 | Pyrrolidone carboxylic acid | ||||
Sequence: Q | ||||||
Chain | PRO_0000445412 | 25-357 | Glypican-3 alpha subunit | |||
Sequence: QPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQMMNPGLPESVLDINECLRGARRDLKVFGSFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNGGKLTTTIGKLCAHSQQRQYR | ||||||
Disulfide bond | 34↔71 | |||||
Sequence: CHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTC | ||||||
Disulfide bond | 64↔261 | |||||
Sequence: CLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQMMNPGLPESVLDINECLRGARRDLKVFGSFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYC | ||||||
Disulfide bond | 72↔264 | |||||
Sequence: CSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQMMNPGLPESVLDINECLRGARRDLKVFGSFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYC | ||||||
Glycosylation | 123 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 196↔348 | |||||
Sequence: CLRGARRDLKVFGSFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNGGKLTTTIGKLC | ||||||
Glycosylation | 240 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 251↔284 | |||||
Sequence: CGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGC | ||||||
Disulfide bond | 273↔421 | Interchain (between alpha and beta chains) | ||||
Sequence: CGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNGGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKILKVAHVEHEETLSSRRRELIQKLKSFINFYSALPGYICSHSPVAENDTLC | ||||||
Disulfide bond | 277↔409 | Interchain (between alpha and beta chains) | ||||
Sequence: CNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNGGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKILKVAHVEHEETLSSRRRELIQKLKSFINFYSALPGYIC | ||||||
Modified residue | 351 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000445413 | 358-553 | Glypican-3 beta subunit | |||
Sequence: SAYYPEDLFIDKKILKVAHVEHEETLSSRRRELIQKLKSFINFYSALPGYICSHSPVAENDTLCWNGQELVERYSQKAARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSVPKGKVLDKSLDEEGLESGDCGDDEDECIGSSGDGMVKVKNQLRFLAELAYDLDVDDAPGNKQHGNQKDNEITTSHS | ||||||
Glycosylation | 417 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 494 | O-linked (Xyl...) (glycosaminoglycan) serine | ||||
Sequence: S | ||||||
Glycosylation | 508 | O-linked (Xyl...) (glycosaminoglycan) serine | ||||
Sequence: S | ||||||
Lipidation | 553 | GPI-anchor amidated serine | ||||
Sequence: S | ||||||
Propeptide | PRO_0000012312 | 554-579 | Removed in mature form | |||
Sequence: VGNMPSPLKILISVAIYVACFFFLVH |
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
- PTM
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).
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).
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
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 533-552 | Disordered | ||||
Sequence: DAPGNKQHGNQKDNEITTSH |
Sequence similarities
Belongs to the glypican family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length579
- Mass (Da)65,332
- Last updated2003-03-01 v1
- Checksum066C23B3493A9346
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B1ATR5 | B1ATR5_MOUSE | Gpc3 | 430 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
BC036126 EMBL· GenBank· DDBJ | AAH36126.1 EMBL· GenBank· DDBJ | mRNA |