GPC3_DANRE
ID GPC3_DANRE Reviewed; 590 AA.
AC Q6V9Y8;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Glypican-3 {ECO:0000303|PubMed:14610063};
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 {ECO:0000312|ZFIN:ZDB-GENE-031212-1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:AAR05100.1};
RN [1] {ECO:0000312|EMBL:AAR05100.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, TISSUE SPECIFICITY,
RP CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 348-ARG--ARG-351.
RX PubMed=14610063; DOI=10.1083/jcb.200302152;
RA De Cat B., Muyldermans S.Y., Coomans C., Degeest G., Vanderschueren B.,
RA Creemers J., Biemar F., Peers B., David G.;
RT "Processing by proprotein convertases is required for glypican-3 modulation
RT of cell survival, Wnt signaling, and gastrulation movements.";
RL J. Cell Biol. 163:625-635(2003).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate (By
CC similarity). Negatively regulates the hedgehog signaling pathway (By
CC similarity). Positively regulates the canonical and non-canonical Wnt
CC signaling pathways (By similarity). Binds to CD81 which decreases the
CC availability of free CD81 for binding to the transcriptional repressor
CC HHEX, 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 similarity). Modulates the effects of growth factors on
CC renal branching morphogenesis (By similarity). Required for coronary
CC vascular development (By similarity). Plays a role in regulating cell
CC movements during gastrulation (PubMed:14610063).
CC {ECO:0000250|UniProtKB:P51654, ECO:0000250|UniProtKB:Q8CFZ4,
CC ECO:0000269|PubMed:14610063}.
CC -!- SUBUNIT: Heterodimer; disulfide-linked. Cleavage by a furin-like
CC convertase results in production of alpha and beta chains which form a
CC disulfide-linked heterodimer. {ECO:0000269|PubMed:14610063}.
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 -!- TISSUE SPECIFICITY: Maternally expressed and is almost ubiquitous
CC during blastula and gastrula stages but becomes restricted to the
CC prospective hindbrain by 24 hours post-fertilization.
CC {ECO:0000269|PubMed:14610063}.
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
CC (PubMed:14610063). This processing is essential for its role in
CC inhibition of hedgehog signaling (By similarity). A second proteolytic
CC event may result in cleavage of the protein on the cell surface,
CC separating it from the GPI-anchor and leading to its shedding from the
CC cell surface (By similarity). {ECO:0000250|UniProtKB:P51654,
CC ECO:0000269|PubMed:14610063}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in severe defects
CC during epiboly with most embryos arrested at 60-80% epiboly.
CC {ECO:0000269|PubMed:14610063}.
CC -!- SIMILARITY: Belongs to the glypican family.
CC {ECO:0000255|RuleBase:RU003518}.
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DR EMBL; AY346090; AAR05100.1; -; mRNA.
DR EMBL; BX248522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX511227; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX537135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT997821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001292547.1; NM_001305618.1.
DR AlphaFoldDB; Q6V9Y8; -.
DR SMR; Q6V9Y8; -.
DR STRING; 7955.ENSDARP00000039553; -.
DR PaxDb; Q6V9Y8; -.
DR Ensembl; ENSDART00000173108; ENSDARP00000142166; ENSDARG00000032199.
DR GeneID; 387365; -.
DR KEGG; dre:387365; -.
DR CTD; 2719; -.
DR ZFIN; ZDB-GENE-031212-1; gpc3.
DR eggNOG; KOG3821; Eukaryota.
DR GeneTree; ENSGT01050000244955; -.
DR OMA; EYICSHS; -.
DR OrthoDB; 1097767at2759; -.
DR PhylomeDB; Q6V9Y8; -.
DR Reactome; R-DRE-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-DRE-2022928; HS-GAG biosynthesis.
DR Reactome; R-DRE-2024096; HS-GAG degradation.
DR Reactome; R-DRE-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-DRE-8957275; Post-translational protein phosphorylation.
DR Reactome; R-DRE-975634; Retinoid metabolism and transport.
DR SignaLink; Q6V9Y8; -.
DR PRO; PR:Q6V9Y8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000032199; Expressed in mature ovarian follicle and 13 other tissues.
DR GO; GO:0046658; C:anchored component of plasma membrane; IBA:GO_Central.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IMP:ZFIN.
DR GO; GO:0060976; P:coronary vasculature development; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:ZFIN.
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 PANTHER; PTHR10822; PTHR10822; 1.
DR PANTHER; PTHR10822:SF4; PTHR10822:SF4; 1.
DR Pfam; PF01153; Glypican; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; Heparan sulfate;
KW Lipoprotein; Membrane; Proteoglycan; Reference proteome; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..351
FT /note="Glypican-3 alpha subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445407"
FT CHAIN 352..?
FT /note="Glypican-3 beta subunit"
FT /evidence="ECO:0000250|UniProtKB:P51654"
FT /id="PRO_0000445408"
FT PROPEP ?..590
FT /note="Removed in mature form"
FT /id="PRO_0000445409"
FT REGION 429..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 476..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 430..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..513
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 504
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000305"
FT CARBOHYD 517
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000305"
FT DISULFID 30..67
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 60..255
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 68..258
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 190..342
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 245..278
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 267..418
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT DISULFID 271..406
FT /note="Interchain (between alpha and beta chains)"
FT /evidence="ECO:0000250|UniProtKB:P35052"
FT MUTAGEN 348..351
FT /note="RVSR->AVSA: Abolishes proteolytic processing."
FT /evidence="ECO:0000269|PubMed:14610063"
SQ SEQUENCE 590 AA; 64512 MW; 95FBEDEE11B1865E CRC64;
MMPGLKLYGA LILCVLVLPF SRPSSQVLDC REVRSSFQFL YPGMKWTPET PVSGSDLQVC
QPKGLTCCSR KMEERYLLIA KQNMESSLQA TSAQLKGLII QNAALFQEAF DMVLRLGRNS
TLMVLREEFP GLGAGASGAV TQLFLDMSLY ILGSDANVND MVSTFFSRLF PLTYRRLLGN
GAVAGISEEC LRGAWKGSSA YGSFPKMMMT RLSRSLLATR VFLQALNLGI EVVNTTQHLR
AGRDCGRSLL KLWYCPHCQS LLEARPCRPL CVSTMGACLG GTTEVQPHWR AYVDELGSLA
AAMKGEQDIE AVVLRLHVII RQALKQAVAS KSKVSAQVSG MCVHAPPRVS RAVPVSAEHT
SASTVNHNRP PMNFDPDETL FGRRREFISG LRGFSQFYSG LGEALCSKEP TSLNSSLCWN
GQEMTDKFPG PGLKRVHPHG SESKQKTPEP VISQIIDKLK HINQLLRMVT LPEKRWRARQ
GGGGARRNPS GPGQTDEDEE GLESGDCDDE DECTGVSGLG PPPRRKRLRI FADLADNLAI
DDLTLHELLL TPRLATDAHG GSSIPGAAHV PTAAFIFTIT IIIFITLGLQ
