| IED ID | IndEnz0002003575 |
| Enzyme Type ID | protease003575 |
| Protein Name |
Glypican-3 GTR2-2 Intestinal protein OCI-5 MXR7 Cleaved into: Glypican-3 alpha subunit; Glypican-3 beta subunit |
| Gene Name | GPC3 OCI5 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAGTVRTACLVVAMLLSLDFPGQAQPPPPPPDATCHQVRSFFQRLQPGLKWVPETPVPGSDLQVCLPKGPTCCSRKMEEKYQLTARLNMEQLLQSASMELKFLIIQNAAVFQEAFEIVVRHAKNYTNAMFKNNYPSLTPQAFEFVGEFFTDVSLYILGSDINVDDMVNELFDSLFPVIYTQLMNPGLPDSALDINECLRGARRDLKVFGNFPKLIMTQVSKSLQVTRIFLQALNLGIEVINTTDHLKFSKDCGRMLTRMWYCSYCQGLMMVKPCGGYCNVVMQGCMAGVVEIDKYWREYILSLEELVNGMYRIYDMENVLLGLFSTIHDSIQYVQKNAGKLTTTIGKLCAHSQQRQYRSAYYPEDLFIDKKVLKVAHVEHEETLSSRRRELIQKLKSFISFYSALPGYICSHSPVAENDTLCWNGQELVERYSQKAARNGMKNQFNLHELKMKGPEPVVSQIIDKLKHINQLLRTMSMPKGRVLDKNLDEEGFESGDCGDDEDECIGGSGDGMIKVKNQLRFLAELAYDLDVDDAPGNSQQATPKDNEISTFHNLGNVHSPLKLLTSMAISVVCFFFLVH |
| Enzyme Length | 580 |
| Uniprot Accession Number | P51654 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: 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). {ECO:0000250|UniProtKB:Q6V9Y8, ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:14610063, ECO:0000269|PubMed:16227623, ECO:0000269|PubMed:17549790, ECO:0000269|PubMed:24496449}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Chain (2); Disulfide bond (7); Glycosylation (5); Lipidation (1); Modified residue (2); Mutagenesis (6); Natural variant (2); Propeptide (1); Signal peptide (1); Site (1) |
| Keywords | Alternative splicing;Cell membrane;Direct protein sequencing;Disease variant;Disulfide bond;GPI-anchor;Glycoprotein;Heparan sulfate;Lipoprotein;Membrane;Phosphoprotein;Protease inhibitor;Proteoglycan;Pyrrolidone carboxylic acid;Reference proteome;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14610063}; Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P13265}; Extracellular side {ECO:0000250|UniProtKB:P13265}. |
| Modified Residue | MOD_RES 25; /note=Pyrrolidone carboxylic acid; /evidence=ECO:0000269|PubMed:29345911; MOD_RES 352; /note=Phosphoserine; by FAM20C; /evidence=ECO:0000269|PubMed:26091039 |
| Post Translational Modification | PTM: O-glycosylated; contains heparan sulfate. {ECO:0000269|PubMed:14610063}.; PTM: 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). {ECO:0000269|PubMed:14610063, ECO:0000269|PubMed:25653284}. |
| Signal Peptide | SIGNAL 1..24; /evidence=ECO:0000269|PubMed:29345911 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10446189; 10473568; 10480354; 10506123; 10639137; 10644753; 10677367; 10716625; 10842173; 11027606; 11087757; 11099377; 11169766; 11274177; 11279150; 11391482; 11551958; 11893651; 12085187; 12138164; 12441129; 12478660; 12492399; 12522689; 12816733; 12824919; 12927802; 14661052; 14993226; 15083193; 15211654; 15294915; 15461586; 15475451; 15583000; 15647514; 16299239; 16343444; 16675560; 16682817; 17087938; 17194707; 17581422; 17603795; 17949778; 17949790; 18264086; 18277882; 18413366; 18462363; 18469798; 18507396; 18511877; 1856611; 18785116; 18813128; 18813403; 18976006; 19215053; 19231003; 19329941; 19344451; 19405109; 19496787; 19513517; 19574883; 19793164; 19816934; 19838081; 20546340; 20554947; 20560209; 20560210; 20653060; 20691685; 20701957; 20725905; 20803547; 20845507; 20868507; 20950395; 20964802; 21187490; 21303616; 21371925; 21410073; 21429352; 21493758; 21556932; 21586223; 21617840; 21655958; 21763480; 21822558; 21847365; 21919070; 21937079; 22026458; 22119409; 22298472; 22382024; 22448662; 22449976; 22706665; 22865282; 23060277; 23079207; 23084579; 23114924; 23192642; 23327927; 23348905; 23414517; 23471984; 23530909; 23558072; 23598528; 23606591; 23624389; 23643963; 23664117; 23664118; 23743582; 24115482; 24186850; 24207089; 24225756; 24236824; 24362268; 24439425; 24443026; 24459012; 24460300; 24492943; 24498024; 24521523; 24548704; 24747240; 24804215; 24841158; 24876756; 25115442; 25168166; 25195714; 25270552; 25344940; 25366870; 25432695; 25542894; 25572615; 25619476; 25735325; 25784484; 25822763; 25862856; 25896897; 25967456; 26052074; 26256079; 26332121; 26345955; 26370140; 26502856; 26722522; 26755876; 26764243; 26977595; 27102087; 27259271; 27286460; 27507057; 27530312; 27573079; 27647326; 27689616; 27758865; 2793848; 28087980; 28371070; 28378832; 28429175; 28432433; 28476031; 28636109; 28812296; 29106433; 29226636; 29398870; 29563582; 29582639; 29623600; 29637653; 29708315; 29807831; 29901640; 29916268; 29935166; 30267212; 30573358; 30592149; 30729617; 30803713; 30827508; 30854929; 31028536; 31053802; 31160489; 31179679; 31612616; 31706332; 31761395; 31774932; 31781603; 32017945; 32620659; 32891543; 33239522; 33429083; 33453658; 33512817; 33726759; 34003580; 34112123; 34325726; 34590489; 34715880; 6496574; 7550340; 7601448; 7683668; 7711731; 8782816; 8894688; 8981950; 9326317; 9346953; 9463333; 9506957; 9535912; 9620772; 9892646; 9915799; 9925661; 9988767; |
| Motif | |
| Gene Encoded By | |
| Mass | 65,563 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |