PRIO_AOTTR
ID PRIO_AOTTR Reviewed; 239 AA.
AC P40245;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: Full=PrP27-30;
DE AltName: Full=PrP33-35C;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor; Fragment;
GN Name=PRNP; Synonyms=PRP;
OS Aotus trivirgatus (Three-striped night monkey) (Douroucouli).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Aotidae;
OC Aotus.
OX NCBI_TaxID=9505;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7837269; DOI=10.1006/jmbi.1994.0030;
RA Schaetzl H.M., Da Costa M., Taylor L., Cohen F.E., Prusiner S.B.;
RT "Prion protein gene variation among primates.";
RL J. Mol. Biol. 245:362-374(1995).
CC -!- FUNCTION: Its primary physiological function is unclear. May play a
CC role in neuronal development and synaptic plasticity. May be required
CC for neuronal myelin sheath maintenance. May promote myelin homeostasis
CC through acting as an agonist for ADGRG6 receptor. 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) (By
CC similarity). Association with GPC1 (via its heparan sulfate chains)
CC targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the
CC ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate
CC side chains (By 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 SYN1
CC (By similarity). Mislocalized cytosolically exposed PrP interacts with
CC MGRN1; this interaction alters MGRN1 subcellular location and causes
CC lysosomal enlargement (By similarity). Interacts with APP. Interacts
CC with KIAA1191 (By similarity). Interacts with ADGRG6 (By similarity).
CC {ECO:0000250|UniProtKB:P04156, 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=PrP is found in high quantity in the brain of humans and
CC animals infected with the degenerative neurological diseases 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; U08293; AAC50082.1; -; Genomic_DNA.
DR PIR; S53633; S53633.
DR AlphaFoldDB; P40245; -.
DR BMRB; P40245; -.
DR SMR; P40245; -.
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..15
FT /evidence="ECO:0000250"
FT CHAIN 16..222
FT /note="Major prion protein"
FT /id="PRO_0000025613"
FT PROPEP 223..>239
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025614"
FT REPEAT 44..51
FT /note="1"
FT REPEAT 52..59
FT /note="2"
FT REPEAT 60..67
FT /note="3"
FT REPEAT 68..75
FT /note="4"
FT REPEAT 76..83
FT /note="5"
FT REGION 15..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 16..222
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 16..31
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 44..83
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT COMPBIAS 28..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 53
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 54
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 55
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 61
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 62
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 63
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 69
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 70
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 71
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 77
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 78
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 79
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 222
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 171..206
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT NON_TER 1
FT NON_TER 239
SQ SEQUENCE 239 AA; 26246 MW; 2EFB77E354B7024A CRC64;
MLVLFVATWS DLGLCKKRPK PGGWNTGGSR YPGQSSPGGN RYPPQSGGWG QPHGGGWGQP
HGGGWGQPHG GGWGQPHGGG WGQGGGTHNQ WNKPSKPKTN MKHMAGAAAA GAVVGGLGGY
MLGSAMSRPL IHFGNDYEDR YYRENMYRYP NQVYYRPVDQ YSNQNNFVHD CVNITIKQHT
VTTTTKGENF TETDVKIMER VVEQMCITQY EKESQAYYQR GSSMVLFSSP PVILLISFL
