PRIO_OVICA
ID PRIO_OVICA Reviewed; 256 AA.
AC Q7JIH3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP;
OS Ovis canadensis (Bighorn sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=37174;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RA O'Rourke K.I., Spraker T.R., Wild M.A., Miller M.W.;
RT "PrP gene sequence for big horn sheep (Ovis canadensis).";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Its primary physiological function is unclear. Has
CC cytoprotective activity against internal or environmental stresses. May
CC play a role in neuronal development and synaptic plasticity. May be
CC required for neuronal myelin sheath maintenance. May play a role in
CC iron uptake and iron homeostasis. Soluble oligomers are toxic to
CC cultured neuroblastoma cells and induce apoptosis (in vitro).
CC Association with GPC1 (via its heparan sulfate chains) targets PRNP to
CC lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated
CC GPC1 deaminase degradation of its heparan sulfate side chains (By
CC similarity). {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Soluble oligomers may represent an
CC intermediate stage on the path to fibril formation. Copper binding may
CC promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and
CC SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this
CC interaction alters MGRN1 subcellular location and causes lysosomal
CC enlargement. Interacts with KIAA1191. {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04156};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P04156}. Golgi
CC apparatus {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts
CC via association with the heparan sulfate chains of GPC1. Colocates, in
CC the presence of Cu(2+), to vesicles in para- and perinuclear regions,
CC where both proteins undergo internalization. Heparin displaces PRNP
CC from lipid rafts and promotes endocytosis.
CC {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: The normal, monomeric form has a mainly alpha-helical
CC structure. The disease-associated, protease-resistant form forms
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Disease mutations may favor
CC intermolecular contacts via short beta strands, and may thereby trigger
CC oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. At
CC low copper concentrations, the sidechains of His residues from three or
CC four repeats contribute to the binding of a single copper ion.
CC Alternatively, a copper ion can be bound by interaction with the
CC sidechain and backbone amide nitrogen of a single His residue. The
CC observed copper binding stoichiometry suggests that two repeat regions
CC cooperate to stabilize the binding of a single copper ion. At higher
CC copper concentrations, each octamer can bind one copper ion by
CC interactions with the His sidechain and Gly backbone atoms. A mixture
CC of binding types may occur, especially in the case of octamer repeat
CC expansion. Copper binding may stabilize the conformation of this region
CC and may promote oligomerization. {ECO:0000250|UniProtKB:P04156}.
CC -!- DISEASE: Note=Found in high quantity in the brain of humans and animals
CC infected with degenerative neurological diseases such as kuru,
CC Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS),
CC scrapie, bovine spongiform encephalopathy (BSE), transmissible mink
CC encephalopathy (TME), etc. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; AF166334; AAD48030.1; -; Genomic_DNA.
DR AlphaFoldDB; Q7JIH3; -.
DR SMR; Q7JIH3; -.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR000817; Prion.
DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR InterPro; IPR025860; Prion_N_dom.
DR Pfam; PF00377; Prion; 1.
DR Pfam; PF11587; Prion_bPrPp; 1.
DR PRINTS; PR00341; PRION.
DR SMART; SM00157; PRP; 1.
DR SUPFAM; SSF54098; SSF54098; 1.
DR PROSITE; PS00291; PRION_1; 1.
DR PROSITE; PS00706; PRION_2; 1.
PE 3: Inferred from homology;
KW Amyloid; Cell membrane; Copper; Disulfide bond; Glycoprotein;
KW Golgi apparatus; GPI-anchor; Lipoprotein; Membrane; Metal-binding; Prion;
KW Repeat; Signal; Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000250"
FT CHAIN 25..233
FT /note="Major prion protein"
FT /id="PRO_0000025705"
FT PROPEP 234..256
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025706"
FT REPEAT 54..62
FT /note="1"
FT REPEAT 63..70
FT /note="2"
FT REPEAT 71..78
FT /note="3"
FT REPEAT 79..86
FT /note="4"
FT REPEAT 87..95
FT /note="5"
FT REGION 25..233
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 28..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..95
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 64
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 65
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 66
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 72
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 73
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 74
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 80
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 81
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 82
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 88
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 90
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 91
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 233
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 182..217
FT /evidence="ECO:0000250|UniProtKB:P04273"
SQ SEQUENCE 256 AA; 27887 MW; BFC8E95F6FD99746 CRC64;
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW
GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS QWNKPSKPKT NMKHVAGAAA
AGAVVGGLGG YMLGSAMSRP LIHFGNDYED RYYRENMYRY PNQVYYRPVD QYSNQNNFVH
DCVNITVKQH TVTTTTKGEN FTETDIKIME RVVEQMCITQ YQRESQAYYQ RGASVILFSS
PPVILLISFL IFLIVG
