GPC1_RAT
ID GPC1_RAT Reviewed; 558 AA.
AC P35053;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 128.
DE RecName: Full=Glypican-1;
DE AltName: Full=HSPG M12;
DE Contains:
DE RecName: Full=Secreted glypican-1;
DE Flags: Precursor;
GN Name=Gpc1;
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 PROTEIN SEQUENCE OF 24-55 AND 424-445.
RC TISSUE=Brain;
RX PubMed=1417860; DOI=10.1016/0006-291x(92)92398-h;
RA Karthikeyan L., Maurel P., Rauch U., Margolis R.K., Margolis R.U.;
RT "Cloning of a major heparan sulfate proteoglycan from brain and
RT identification as the rat form of glypican.";
RL Biochem. Biophys. Res. Commun. 188:395-401(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND PROTEIN SEQUENCE OF
RP 83-112; 196-207 AND 422-443.
RC STRAIN=New England Deaconess Hospital;
RX PubMed=8207484; DOI=10.1523/jneurosci.14-06-03713.1994;
RA Litwack E.D., Stipp C.S., Kumbasar A., Lander A.D.;
RT "Neuronal expression of glypican, a cell-surface
RT glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan, in the
RT adult rat nervous system.";
RL J. Neurosci. 14:3713-3724(1994).
RN [3]
RP COPPER-BINDING, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=14707133; DOI=10.1074/jbc.m313678200;
RA Mani K., Cheng F., Havsmark B., David S., Fransson L.A.;
RT "Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the
RT copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan
RT sulfate in rat C6 glioma cells.";
RL J. Biol. Chem. 279:12918-12923(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15383532; DOI=10.1074/jbc.m408837200;
RA Rothblum K., Stahl R.C., Carey D.J.;
RT "Constitutive release of alpha4 type V collagen N-terminal domain by
RT Schwann cells and binding to cell surface and extracellular matrix heparan
RT sulfate proteoglycans.";
RL J. Biol. Chem. 279:51282-51288(2004).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16407548; DOI=10.1523/jneurosci.2544-05.2006;
RA Chernousov M.A., Rothblum K., Stahl R.C., Evans A., Prentiss L.,
RA Carey D.J.;
RT "Glypican-1 and alpha4(V) collagen are required for Schwann cell
RT myelination.";
RL J. Neurosci. 26:508-517(2006).
CC -!- FUNCTION: Cell surface proteoglycan that bears heparan sulfate. May act
CC as a catalyst in increasing the rate of conversion of prion protein
CC PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side
CC chains) with both forms of PRPN, targeting them to lipid rafts and
CC facilitating their interaction. Required for proper skeletal muscle
CC differentiation by sequestering FGF2 in lipid rafts preventing its
CC binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling.
CC Binds Cu(2+) or Zn(2+) ions (By similarity). Binds, via the heparan
CC sulfate side chains, alpha-4 (V) collagen and participates in Schwann
CC cell myelination. {ECO:0000250, ECO:0000269|PubMed:15383532,
CC ECO:0000269|PubMed:16407548}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC Extracellular side. Endosome {ECO:0000250}. Note=S-nitrosylated form
CC recycled in endosomes. Localizes to CAV1-containing vesicles close to
CC the cell surface. Cleavage of heparan sulfate side chains takes place
CC mainly in late endosomes. Associates with both forms of PRNP in lipid
CC rafts. Colocalizes with APP in perinuclear compartments and with CP in
CC intracellular compartments (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Secreted glypican-1]: Secreted, extracellular
CC space {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Nervous system. {ECO:0000269|PubMed:8207484}.
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.
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:14707133}.
CC -!- PTM: This cell-associated glypican is further processed to give rise to
CC a medium-released species.
CC -!- SIMILARITY: Belongs to the glypican family. {ECO:0000305}.
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DR EMBL; L02896; AAA86439.1; -; mRNA.
DR EMBL; L34067; AAA41251.1; -; mRNA.
DR PIR; I56545; I56545.
DR RefSeq; NP_110455.1; NM_030828.1.
DR AlphaFoldDB; P35053; -.
DR SMR; P35053; -.
DR BioGRID; 248661; 2.
DR IntAct; P35053; 1.
DR STRING; 10116.ENSRNOP00000066597; -.
DR GlyGen; P35053; 5 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P35053; -.
DR jPOST; P35053; -.
DR PaxDb; P35053; -.
DR PRIDE; P35053; -.
DR GeneID; 58920; -.
DR KEGG; rno:58920; -.
DR CTD; 2817; -.
DR RGD; 61853; Gpc1.
DR eggNOG; KOG3821; Eukaryota.
DR InParanoid; P35053; -.
DR OrthoDB; 611422at2759; -.
DR PhylomeDB; P35053; -.
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-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-975634; Retinoid metabolism and transport.
DR PRO; PR:P35053; -.
DR Proteomes; UP000002494; Unplaced.
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:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0070052; F:collagen V binding; IPI:RGD.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0017134; F:fibroblast growth factor binding; ISS:UniProtKB.
DR GO; GO:0043236; F:laminin binding; ISS: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; IDA:UniProtKB.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2001016; P:positive regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:1905475; P:regulation of protein localization to membrane; IBA:GO_Central.
DR GO; GO:0014037; P:Schwann cell differentiation; IDA: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; Direct protein sequencing; Disulfide bond; Endosome;
KW Glycoprotein; GPI-anchor; Heparan sulfate; Lipoprotein; Membrane;
KW Proteoglycan; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:1417860"
FT CHAIN 24..530
FT /note="Glypican-1"
FT /id="PRO_0000012299"
FT CHAIN 24..?
FT /note="Secreted glypican-1"
FT /id="PRO_0000333839"
FT PROPEP 531..558
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000012300"
FT REGION 478..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 530
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:14707133"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:14707133"
FT CARBOHYD 486
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 490
FT /note="O-linked (Xyl...) (heparan sulfate) serine"
FT /evidence="ECO:0000255"
FT DISULFID 32..68
FT /evidence="ECO:0000250"
FT DISULFID 62..256
FT /evidence="ECO:0000250"
FT DISULFID 69..259
FT /evidence="ECO:0000250"
FT DISULFID 191..343
FT /evidence="ECO:0000250"
FT DISULFID 246..279
FT /evidence="ECO:0000250"
FT DISULFID 268..415
FT /evidence="ECO:0000250"
FT DISULFID 272..401
FT /evidence="ECO:0000250"
FT CONFLICT 21
FT /note="T -> A (in Ref. 2; AAA41251)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="Y -> N (in Ref. 2; AAA41251)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="A -> G (in Ref. 2; AAA41251)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="I -> G (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 443
FT /note="E -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="I -> T (in Ref. 2; AAA41251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 558 AA; 61734 MW; E2878A854B9A1D7F CRC64;
MELRARGWWL LCAAAALVAC TRGDPASKSR SCSEVRQIYG AKGFSLSDVP QAEISGEHLR
ICPQGYTCCT SEMEENLANH SRMELETALH DSSRALQATL ATQLHGIDDH FQRLLNDSER
TLQDAFPGAF GDLYTQNTRA FRDLYAELRL YYRGANLHLE ETLAEFWARL LERLFKQLHP
QLLLPDDYLD CLGKQAEALR PFGDAPRELR LRATRAFVAA RSFVQGLGVA SDVVRKVAQV
PLAPECSRAV MKLVYCAHCR GVPGARPCPD YCRNVLKGCL ANQADLDAEW RNLLDSMVLI
TDKFWGPSGA EYVIGSVHMW LAEAINALQD NKDTLTAKVI QGCGNPKVNP HGSGPEEKRR
RAKLALQEKS STGTLEKLVS EAKAQLRDIQ DYWISLPGTL CSEKMAMSPA SDDRCWNGIS
KGRYLPEVMG DGLANQINNP EVEVDITKPD MTIRQQIMQL KIMTNRLRGA YGGNDVDFQD
ASDDGSGSGS GGGCPDDACG RRVSKKSSSS RTPLIHALPG LSEQEGQKTS AATRPEPHYF
FLLFLFTLVL AAARPRWR
