GPC3_PANTR
ID GPC3_PANTR Reviewed; 580 AA.
AC A5A6P7;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Glypican-3;
DE AltName: Full=GTR2-2;
DE AltName: Full=Intestinal protein OCI-5;
DE AltName: Full=MXR7;
DE Contains:
DE RecName: Full=Glypican-3 alpha subunit {ECO:0000250|UniProtKB:P51654};
DE Contains:
DE RecName: Full=Glypican-3 beta subunit {ECO:0000250|UniProtKB:P51654};
DE Flags: Precursor;
GN Name=GPC3;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Skin;
RX PubMed=17574350; DOI=10.1016/j.gene.2007.04.013;
RA Sakate R., Suto Y., Imanishi T., Tanoue T., Hida M., Hayasaka I.,
RA Kusuda J., Gojobori T., Hashimoto K., Hirai M.;
RT "Mapping of chimpanzee full-length cDNAs onto the human genome unveils
RT large potential divergence of the transcriptome.";
RL Gene 399:1-10(2007).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate (By
CC similarity). Negatively regulates the hedgehog signaling pathway when
CC attached via the GPI-anchor to the cell surface by competing with the
CC hedgehog receptor PTC1 for binding to hedgehog proteins (By
CC similarity). Binding to the hedgehog protein SHH triggers
CC internalization of the complex by endocytosis and its subsequent
CC lysosomal degradation (By similarity). Positively regulates the
CC canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled
CC and stimulating the binding of the Frizzled receptor to Wnt ligands (By
CC similarity). Positively regulates the non-canonical Wnt signaling
CC pathway (By similarity). Binds to CD81 which decreases the availability
CC of free CD81 for binding to the transcriptional repressor HHEX,
CC resulting in nuclear translocation of HHEX and transcriptional
CC repression (By similarity). Inhibits the dipeptidyl peptidase activity
CC of DPP4 (By similarity). Plays a role in limb patterning and skeletal
CC development by controlling the cellular response to BMP4 (By
CC similarity). Modulates the effects of growth factors BMP2, BMP7 and
CC FGF7 on renal branching morphogenesis (By similarity). Required for
CC coronary vascular development (By similarity). Plays a role in
CC regulating cell movements during gastrulation (By similarity).
CC {ECO:0000250|UniProtKB:P51654, ECO:0000250|UniProtKB:Q6V9Y8,
CC ECO:0000250|UniProtKB:Q8CFZ4}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked (By similarity). Cleavage by a
CC furin-like convertase results in production of alpha and beta chains
CC which form a disulfide-linked heterodimer (By similarity). Interacts
CC with DPP4 (By similarity). Interacts with FGF2 (By similarity).
CC Interacts with WNT5A (By similarity). Also interacts with WNT3A and
CC WNT7B (By similarity). Interacts with hedgehog protein SHH; the heparan
CC sulfate chains are not required for the interaction (By similarity).
CC Also interacts with hedgehog protein IHH (By similarity). Interacts
CC with CD81 (By similarity). Interacts with Wnt receptors FZD4, FZD7 and
CC FZD8; the heparan sulfate chains are required for the interaction (By
CC similarity). {ECO:0000250|UniProtKB:P13265,
CC ECO:0000250|UniProtKB:P51654, ECO:0000250|UniProtKB:Q8CFZ4}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P13265};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P13265}; Extracellular
CC side {ECO:0000250|UniProtKB:P13265}.
CC -!- PTM: O-glycosylated; contains heparan sulfate.
CC {ECO:0000250|UniProtKB:P51654}.
CC -!- PTM: Cleaved intracellularly by a furin-like convertase to generate 2
CC subunits, alpha and beta, which remain associated through disulfide
CC bonds and are associated with the cell surface via the GPI-anchor. This
CC processing is essential for its role in inhibition of hedgehog
CC signaling. A second proteolytic event may result in cleavage of the
CC protein on the cell surface, separating it from the GPI-anchor and
CC leading to its shedding from the cell surface.
CC {ECO:0000250|UniProtKB:P51654}.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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DR EMBL; AB222175; BAF62420.1; -; mRNA.
DR RefSeq; NP_001129209.1; NM_001135737.1.
DR AlphaFoldDB; A5A6P7; -.
DR SMR; A5A6P7; -.
DR STRING; 9598.ENSPTRP00000038390; -.
DR PaxDb; A5A6P7; -.
DR GeneID; 465866; -.
DR KEGG; ptr:465866; -.
DR CTD; 2719; -.
DR eggNOG; KOG3821; Eukaryota.
DR InParanoid; A5A6P7; -.
DR OrthoDB; 1097767at2759; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0046658; C:anchored component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProt.
DR GO; GO:0060422; F:peptidyl-dipeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0042074; P:cell migration involved in gastrulation; ISS:UniProtKB.
DR GO; GO:0072111; P:cell proliferation involved in kidney development; ISS:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0072180; P:mesonephric duct morphogenesis; ISS:UniProtKB.
DR GO; GO:0010466; P:negative regulation of peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR InterPro; IPR001863; Glypican.
DR InterPro; IPR015501; Glypican-3.
DR InterPro; IPR019803; Glypican_CS.
DR PANTHER; PTHR10822; PTHR10822; 1.
DR PANTHER; PTHR10822:SF4; PTHR10822:SF4; 1.
DR Pfam; PF01153; Glypican; 1.
DR PROSITE; PS01207; GLYPICAN; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; Heparan sulfate;
KW Lipoprotein; Membrane; Phosphoprotein; Protease inhibitor; Proteoglycan;
KW Pyrrolidone carboxylic acid; Reference proteome; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..358
FT /note="Glypican-3 alpha subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445414"
FT CHAIN 359..554
FT /note="Glypican-3 beta subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445415"
FT PROPEP 555..580
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000295280"
FT MOD_RES 25
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT LIPID 554
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 509
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT DISULFID 35..72
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 65..262
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 73..265
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 197..349
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 252..285
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 274..422
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 278..410
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
SQ SEQUENCE 580 AA; 65565 MW; E968AECA2F8F8B03 CRC64;
MAGTVRTACL VVAMLLSLDF PGQAQPPPPP PDATCHQVRS FFQRLQPGLK WVPETPVPGS
DLQVCLPKGP TCCSRKMEEK YQLTARLNME QLLQSASKEL KFLIIQNAAV FQEAFEIVVR
HAKNYTNAMF KNNYPSLTPQ AFEFVGEFFT DVSLYILGSD INVDDMVNEL FDSLFPVIYT
QLMNPGLPDS ALDINECLRG ARRDLKVFGN FPKLIMTQVS KSLQVTRIFL QALNLGIEVI
NTTDHLKFSK DCGRMLTRMW YCSYCQGLMM VKPCGGYCNV VMQGCMAGVV EIDKYWREYI
LSLEELVNGM YRIYDMENVL LGLFSTIHDS IQYVQKNAGK LTTTIGKLCA HSQQRQYRSA
YYPEDLFIDK KVLKVARVEH EETLSSRRRE LIQKLKSFIS FYSALPGYIC SHSPVAENDT
LCWNGQELVE RYSQKAARNG MKNQFNLHEL KMKGPEPVVS QIIDKLKHIN QLLRTMSVPK
GRVLDKNLDE EGFESGDCGD DEDECIGGSG DGMMKVKNQL RFLAELAYDL DVDDAPGSNQ
QATPKDNEIS TFHNLGNVHS PLKLLTSMAI SVVCFFFLVH
