Recombinant Human Glypican-3 (GPC3) (G537R), partial (Active)

Function

Cell surface proteoglycan (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)

Subcellular Location

Cell membrane (Lipid-anchor, GPI-anchor)

Disease Association

Simpson-Golabi-Behmel syndrome 1 (SGBS1) : 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Detected in placenta (at protein level) (PubMed:32337544). Highly expressed in lung, liver and kidney

Subunit

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)

• Shen T. et al. Mapping of the Simpson-Golabi-Behmel overgrowth syndrome gene (GPC3) to chromosome X in human and rat by fluorescence in situ hybridization. — Mamm. Genome (1997)
• Pilia G. et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. — Nat. Genet. (1996)
• Lage H. et al. Cloning and characterization of human cDNAs encoding a protein with high homology to rat intestinal development protein OCI-5. — Gene (1997)
• Grozdanov P.N. et al. Expression of the Glypican-3 protein in hepatoma cells. (JAN-)
• Ross M.T. et al. The DNA sequence of the human X chromosome. — Nature (2005)
• Mural R.J. et al. PubMed: CI-56FTJV1JKRRTT (SEP-)
• Huber R. et al. 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. — Genomics (1997)
• Capurro M. et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. — Gastroenterology (2003)