GPC3_RAT
ID GPC3_RAT Reviewed; 597 AA.
AC P13265; Q5U326;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Glypican-3;
DE AltName: Full=Intestinal protein OCI-5;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=3185547; DOI=10.1128/mcb.8.10.4243-4249.1988;
RA Filmus J., Church J.G., Buick R.N.;
RT "Isolation of a cDNA corresponding to a developmentally regulated
RT transcript in rat intestine.";
RL Mol. Cell. Biol. 8:4243-4249(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=7487896; DOI=10.1042/bj3110561;
RA Filmus J., Shi W., Wong Z.M., Wong M.J.;
RT "Identification of a new membrane-bound heparan sulphate proteoglycan.";
RL Biochem. J. 311:561-565(1995).
RN [4]
RP INTERACTION WITH FGF2.
RX PubMed=9065409; DOI=10.1074/jbc.272.12.7574;
RA Song H.H., Shi W., Filmus J.;
RT "OCI-5/rat glypican-3 binds to fibroblast growth factor-2 but not to
RT insulin-like growth factor-2.";
RL J. Biol. Chem. 272:7574-7577(1997).
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 (PubMed:9065409).
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:P51654,
CC ECO:0000250|UniProtKB:Q8CFZ4, ECO:0000269|PubMed:9065409}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7487896};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:7487896}; Extracellular
CC side {ECO:0000269|PubMed:7487896}.
CC -!- DEVELOPMENTAL STAGE: In the intestine, expression decreases gradually
CC from 20 dpc and finally becomes undetectable after weaning around 24
CC days after birth. {ECO:0000269|PubMed:3185547}.
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; M22400; AAA41735.1; -; mRNA.
DR EMBL; BC085756; AAH85756.1; -; mRNA.
DR PIR; A30814; A30814.
DR RefSeq; NP_036906.1; NM_012774.1.
DR AlphaFoldDB; P13265; -.
DR SMR; P13265; -.
DR BioGRID; 247276; 2.
DR STRING; 10116.ENSRNOP00000043344; -.
DR GlyGen; P13265; 5 sites.
DR PaxDb; P13265; -.
DR PRIDE; P13265; -.
DR GeneID; 25236; -.
DR KEGG; rno:25236; -.
DR UCSC; RGD:2725; rat.
DR CTD; 2719; -.
DR RGD; 2725; Gpc3.
DR eggNOG; KOG3821; Eukaryota.
DR InParanoid; P13265; -.
DR OrthoDB; 1097767at2759; -.
DR PhylomeDB; P13265; -.
DR Reactome; R-RNO-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-RNO-2022928; HS-GAG biosynthesis.
DR Reactome; R-RNO-2024096; HS-GAG degradation.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR Reactome; R-RNO-975634; Retinoid metabolism and transport.
DR PRO; PR:P13265; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA: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:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0060422; F:peptidyl-dipeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0009948; P:anterior/posterior axis specification; ISO:RGD.
DR GO; GO:0010171; P:body morphogenesis; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISO:RGD.
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:0072203; P:cell proliferation involved in metanephros development; ISO:RGD.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; ISO:RGD.
DR GO; GO:0072180; P:mesonephric duct morphogenesis; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0045926; P:negative regulation of growth; ISO:RGD.
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:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD.
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:0046326; P:positive regulation of glucose import; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:RGD.
DR GO; GO:2000096; P:positive regulation of Wnt signaling pathway, planar cell polarity pathway; IDA:MGI.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0040008; P:regulation of growth; ISO:RGD.
DR GO; GO:2000050; P:regulation of non-canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
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 1: Evidence at protein 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..357
FT /note="Glypican-3 alpha subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445416"
FT CHAIN 358..?
FT /note="Glypican-3 beta subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445417"
FT PROPEP ?..597
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012314"
FT REGION 533..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 25
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 494
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 508
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT DISULFID 34..71
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 64..261
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 72..264
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 196..348
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 251..284
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 273..421
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 277..409
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT CONFLICT 553
FT /note="S -> N (in Ref. 2; AAH85756)"
FT /evidence="ECO:0000305"
FT CONFLICT 583..584
FT /note="CP -> VSQ (in Ref. 2; AAH85756)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 597 AA; 67049 MW; C556AD4127685687 CRC64;
MAGTVRTACL LVAMLLGLGC LGQAQPPPPP DATCHQVRSF FQRLQPGLKW VPETPVPGSD
LQVCLPKGPT CCSRKMEEKY QLTARLNMEQ LLQSASMELK FLIIQNAAVF QEAFEIVVRH
AKNYTNAMFK NNYPSLTPQA FEFVGEFFTD VSLYILGSDI NVDDMVNELF DSLFPVIYTQ
MMNPGLPESV LDINECLRGA RRDLKVFGSF PKLIMTQVSK SLQVTRIFLQ ALNLGIEVIN
TTDHLKFSKD CGRMLTRMWY CSYCQGLMMV KPCGGYCNVV MQGCMAGVVE IDKYWREYIL
SLEELVNGMY RIYDMENVLL GLFSTIHDSI QYVQKNGGKL TTTIGKLCAH SQQRQYRSAY
YPEDLFIDKK VLKVARVEHE ETLSSRRREL IQKLKSFISF YSALPGYICS HSPVAENDTL
CWNGQELVER YSQKAARNGM KNQFNLHELK MKGPEPVVSQ IIDKLKHINQ LLRTMSVPKG
KVVDKSLDEE GLESGDCGDD EDECIGSSGD GMMKVKNQLR FLAELAYDLD VDDAPGNKQH
GNQKDNEITT SHSVGNMPSP LKILISVAIY VACFFSWCTD LPCPCLCCPA APCGPPT
