GPC1_MOUSE
ID GPC1_MOUSE Reviewed; 557 AA.
AC Q9QZF2;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Glypican-1;
DE Contains:
DE RecName: Full=Secreted glypican-1;
DE Flags: Precursor;
GN Name=Gpc1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11474185; DOI=10.1159/000056954;
RA Szpirer C., Szpirer J., Riviere M., Van Vooren P., Veugelers M., David G.;
RT "Mapping of the rat glypican genes.";
RL Cytogenet. Cell Genet. 93:83-86(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 COPPER-BINDING, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=12732622; DOI=10.1074/jbc.m300394200;
RA Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.;
RT "Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-
RT nitroso-dependent autocleavage of glypican-1 heparan sulfate.";
RL J. Biol. Chem. 278:38956-38965(2003).
RN [4]
RP SUBCELLULAR LOCATION, COPPER-BINDING, ZINC-BINDING, S-NITROSYLATION, AND
RP GLYCOSYLATION.
RX PubMed=15677459; DOI=10.1074/jbc.m409179200;
RA Cappai R., Cheng F., Ciccotosto G.D., Needham B.E., Masters C.L.,
RA Multhaup G., Fransson L.A., Mani K.;
RT "The amyloid precursor protein (APP) of Alzheimer disease and its paralog,
RT APLP2, modulate the Cu/Zn-nitric oxide-catalyzed degradation of glypican-1
RT heparan sulfate in vivo.";
RL J. Biol. Chem. 280:13913-13920(2005).
RN [5]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=16971378; DOI=10.1093/glycob/cwl045;
RA Mani K., Cheng F., Fransson L.A.;
RT "Constitutive and vitamin C-induced, NO-catalyzed release of heparan
RT sulfate from recycling glypican-1 in late endosomes.";
RL Glycobiology 16:1251-1261(2006).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=16923158; DOI=10.1111/j.1471-4159.2006.03981.x;
RA Cheng F., Lindqvist J., Haigh C.L., Brown D.R., Mani K.;
RT "Copper-dependent co-internalization of the prion protein and glypican-1.";
RL J. Neurochem. 98:1445-1457(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [8]
RP GLYCOSYLATION, AND ASSOCIATION WITH PRPN AND AN ANIMAL MODEL OF SCRAPIE
RP DISEASE.
RX PubMed=18717736; DOI=10.1111/j.1460-9568.2008.06386.x;
RA Lofgren K., Cheng F., Fransson L.A., Bedecs K., Mani K.;
RT "Involvement of glypican-1 autoprocessing in scrapie infection.";
RL Eur. J. Neurosci. 28:964-972(2008).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-79 AND ASN-116.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=19732411; DOI=10.1186/1749-8104-4-33;
RA Jen Y.H., Musacchio M., Lander A.D.;
RT "Glypican-1 controls brain size through regulation of fibroblast growth
RT factor signaling in early neurogenesis.";
RL Neural Dev. 4:33-33(2009).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND ASSOCIATION WITH A MOUSE MODEL OF
RP SCRAPIE DISEASE.
RX PubMed=19936054; DOI=10.1371/journal.ppat.1000666;
RA Taylor D.R., Whitehouse I.J., Hooper N.M.;
RT "Glypican-1 mediates both prion protein lipid raft association and disease
RT isoform formation.";
RL PLoS Pathog. 5:E1000666-E1000666(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20100867; DOI=10.1128/mcb.01164-09;
RA Gutierrez J., Brandan E.;
RT "A novel mechanism of sequestering fibroblast growth factor 2 by glypican
RT in lipid rafts, allowing skeletal muscle differentiation.";
RL Mol. Cell. Biol. 30:1634-1649(2010).
RN [14]
RP ASSOCIATION WITH PANCREATIC DUCTAL ADENOCARCINOMAS, DISRUPTION PHENOTYPE,
RP AND FUNCTION.
RX PubMed=21996748; DOI=10.1038/onc.2011.430;
RA Whipple C.A., Young A.L., Korc M.;
RT "A Kras(G12D)-driven genetic mouse model of pancreatic cancer requires
RT glypican-1 for efficient proliferation and angiogenesis.";
RL Oncogene 31:2535-2544(2012).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Binds,
CC via the heparan sulfate side chains, alpha-4 (V) collagen and
CC participates in Schwann cell myelination (By similarity). May act as a
CC catalyst in increasing the rate of conversion of prion protein PRPN(C)
CC to PRNP(Sc) via associating (via the heparan sulfate side chains) with
CC both forms of PRPN, targeting them to lipid rafts and facilitating
CC their interaction. Required for proper skeletal muscle differentiation
CC by sequestering FGF2 in lipid rafts preventing its binding to receptors
CC (FGFRs) and inhibiting the FGF-mediated signaling. Binds Cu(2+) or
CC Zn(2+) ions. {ECO:0000250, ECO:0000269|PubMed:19732411,
CC ECO:0000269|PubMed:19936054, ECO:0000269|PubMed:20100867,
CC ECO:0000269|PubMed:21996748}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC Extracellular side. Endosome. Note=S-nitrosylated form recycled in
CC endosomes. Localizes to CAV1-containing vesicles close to the cell
CC surface. Cleavage of heparan sulfate side chains takes place mainly in
CC late endosomes. Associates with both forms of PRNP in lipid rafts.
CC Colocalizes with APP in perinuclear compartments and with CP in
CC intracellular compartments. Associates with fibrillar APP amyloid-beta
CC peptides in lipid rafts in Alzheimer disease brains.
CC -!- SUBCELLULAR LOCATION: [Secreted glypican-1]: Secreted, extracellular
CC space.
CC -!- PTM: S-nitrosylated in a Cu(2+)-dependent manner. Nitric acid (NO) is
CC released from the nitrosylated cysteines by ascorbate or by some other
CC reducing agent, in a Cu(2+) or Zn(2+) dependent manner. This free
CC nitric oxide is then capable of cleaving the heparan sulfate side
CC chains. {ECO:0000269|PubMed:15677459}.
CC -!- PTM: N- and O-glycosylated. N-glycosylation is mainly of the complex
CC type containing sialic acid. O-glycosylated with heparan sulfate. The
CC heparan sulfate chains can be cleaved either by the action of
CC heparanase or, degraded by a deaminative process that uses nitric oxide
CC (NO) released from the S-nitrosylated cysteines. This process is
CC triggered by ascorbate, or by some other reducing agent, in a
CC Cu(2+)- or Zn(2+) dependent manner. Cu(2+) ions are provided by
CC ceruloproteins such as APP, PRNP or CP which associate with GCP1 in
CC intracellular compartments or lipid rafts.
CC {ECO:0000269|PubMed:12732622, ECO:0000269|PubMed:15677459,
CC ECO:0000269|PubMed:16971378, ECO:0000269|PubMed:18717736,
CC ECO:0000269|PubMed:19656770}.
CC -!- PTM: This cell-associated glypican is further processed to give rise to
CC a medium-released species. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Null mice with induced pancreatic ductal
CC adenocarcinomas (PDACs) exhibit attenuated pancreatic tumor growth and
CC invasiveness, decreased cancer cell proliferation and mitogen-activated
CC protein kinase activation. Pancreatic cancer cells isolated from the
CC tumors of GPC1 (-/-) mice were not as invasive in response to
CC fibroblast growth factor-2 (FGF-2) as cancer cells isolated from wild-
CC type mice. {ECO:0000269|PubMed:19732411, ECO:0000269|PubMed:21996748}.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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DR EMBL; AF185613; AAD56243.1; -; mRNA.
DR EMBL; BC062902; AAH62902.1; -; mRNA.
DR CCDS; CCDS15177.1; -.
DR RefSeq; NP_057905.1; NM_016696.4.
DR AlphaFoldDB; Q9QZF2; -.
DR SMR; Q9QZF2; -.
DR BioGRID; 200012; 4.
DR IntAct; Q9QZF2; 1.
DR MINT; Q9QZF2; -.
DR STRING; 10090.ENSMUSP00000047199; -.
DR GlyGen; Q9QZF2; 5 sites.
DR iPTMnet; Q9QZF2; -.
DR PhosphoSitePlus; Q9QZF2; -.
DR MaxQB; Q9QZF2; -.
DR PaxDb; Q9QZF2; -.
DR PRIDE; Q9QZF2; -.
DR ProteomicsDB; 271314; -.
DR Antibodypedia; 34516; 349 antibodies from 34 providers.
DR DNASU; 14733; -.
DR Ensembl; ENSMUST00000045970; ENSMUSP00000047199; ENSMUSG00000034220.
DR GeneID; 14733; -.
DR KEGG; mmu:14733; -.
DR UCSC; uc007cbs.1; mouse.
DR CTD; 2817; -.
DR MGI; MGI:1194891; Gpc1.
DR VEuPathDB; HostDB:ENSMUSG00000034220; -.
DR eggNOG; KOG3821; Eukaryota.
DR GeneTree; ENSGT01050000244897; -.
DR HOGENOM; CLU_024658_2_0_1; -.
DR InParanoid; Q9QZF2; -.
DR OMA; YCAHCRG; -.
DR OrthoDB; 611422at2759; -.
DR PhylomeDB; Q9QZF2; -.
DR TreeFam; TF105317; -.
DR Reactome; R-MMU-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR Reactome; R-MMU-2024096; HS-GAG degradation.
DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-MMU-376176; Signaling by ROBO receptors.
DR Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR BioGRID-ORCS; 14733; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Gpc1; mouse.
DR PRO; PR:Q9QZF2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9QZF2; protein.
DR Bgee; ENSMUSG00000034220; Expressed in vault of skull and 307 other tissues.
DR ExpressionAtlas; Q9QZF2; baseline and differential.
DR Genevisible; Q9QZF2; MM.
DR GO; GO:0046658; C:anchored component of plasma membrane; IEA:InterPro.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0070052; F:collagen V binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0017134; F:fibroblast growth factor binding; IDA:UniProtKB.
DR GO; GO:0043236; F:laminin binding; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0030200; P:heparan sulfate proteoglycan catabolic process; ISS:UniProtKB.
DR GO; GO:0032288; P:myelin assembly; ISS:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; IEP:UniProtKB.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR GO; GO:0014037; P:Schwann cell differentiation; ISS:UniProtKB.
DR InterPro; IPR001863; Glypican.
DR InterPro; IPR015502; Glypican-1.
DR InterPro; IPR019803; Glypican_CS.
DR PANTHER; PTHR10822; PTHR10822; 1.
DR PANTHER; PTHR10822:SF8; PTHR10822:SF8; 1.
DR Pfam; PF01153; Glypican; 1.
DR PROSITE; PS01207; GLYPICAN; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Copper; Disulfide bond; Endosome; Glycoprotein; GPI-anchor;
KW Heparan sulfate; Lipoprotein; Membrane; Proteoglycan; Reference proteome;
KW S-nitrosylation; Secreted; Signal; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000250"
FT CHAIN 24..529
FT /note="Glypican-1"
FT /id="PRO_0000012297"
FT CHAIN 24..?
FT /note="Secreted glypican-1"
FT /id="PRO_0000333838"
FT PROPEP 530..557
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012298"
FT REGION 477..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..531
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 529
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 485
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 487
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 489
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT DISULFID 32..68
FT /evidence="ECO:0000250"
FT DISULFID 62..255
FT /evidence="ECO:0000250"
FT DISULFID 69..258
FT /evidence="ECO:0000250"
FT DISULFID 190..342
FT /evidence="ECO:0000250"
FT DISULFID 245..278
FT /evidence="ECO:0000250"
FT DISULFID 267..414
FT /evidence="ECO:0000250"
FT DISULFID 271..400
FT /evidence="ECO:0000250"
SQ SEQUENCE 557 AA; 61360 MW; 58A9A24955D16A0B CRC64;
MELRTRGWWL LCAAAALVVC ARGDPASKSR SCSEVRQIYG AKGFSLSDVP QAEISGEHLR
ICPQGYTCCT SEMEENLANH SRMELESALH DSSRALQATL ATQLHGIDDH FQRLLNDSER
TLQEAFPGAF GDLYTQNTRA FRDLYAELRL YYRGANLHLE ETLAEFWARL LERLFKQLHP
QLLPDDYLDC LGKQAEALRP FGDAPRELRL RATRAFVAAR SFVQGLGVAS DVVRKVAQVP
LAPECSRAIM KLVYCAHCRG VPGARPCPDY CRNVLKGCLA NQADLDAEWR NLLDSMVLIT
DKFWGPSGAE SVIGGVHVWL AEAINALQDN KDTLTAKVIQ ACGNPKVNPH GSGPEEKRRR
GKLALQEKPS TGTLEKLVSE AKAQLRDIQD FWISLPGTLC SEKMAMSPAS DDRCWNGISK
GRYLPEVMGD GLANQINNPE VEVDITKPDM TIRQQIMQLK IMTNRLRGAY GGNDVDFQDA
SDDGSGSGSG GGCPDDTCGR RVSKKSSSSR TPLTHALPGL SEQEGQKTSA ATCPEPHSFF
LLFLVTLVLA AARPRWR
