PRIO_BOBOX
ID PRIO_BOBOX Reviewed; 264 AA.
AC B5SY89; B5T9Q3; B6S1H5; B6S1P8;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: Full=Major scrapie-associated fibril protein 1;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP;
OS Bos indicus x Bos taurus (Hybrid cattle).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=30522;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-154.
RX PubMed=18808703; DOI=10.1186/1746-6148-4-36;
RA Brunelle B.W., Greenlee J.J., Seabury C.M., Brown C.E. II, Nicholson E.M.;
RT "Frequencies of polymorphisms associated with BSE resistance differ
RT significantly between Bos taurus, Bos indicus, and composite cattle.";
RL BMC Vet. Res. 4:36-36(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT H-TYPE BSE LYS-211.
RX PubMed=18698343; DOI=10.1371/journal.pone.0002912;
RA Nicholson E.M., Brunelle B.W., Richt J.A., Kehrli M.E. Jr., Greenlee J.J.;
RT "Identification of a heritable polymorphism in bovine PRNP associated with
RT genetic transmissible spongiform encephalopathy: evidence of heritable
RT BSE.";
RL PLoS ONE 3:E2912-E2912(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT H-TYPE BSE LYS-211.
RX PubMed=18787697; DOI=10.1371/journal.ppat.1000156;
RA Richt J.A., Hall S.M.;
RT "BSE case associated with prion protein gene mutation.";
RL PLoS Pathog. 4:E1000156-E1000156(2008).
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=Variations in PRNP are responsible of transmissible
CC bovine spongiform encephalopathies (BSE), a class of neurodegenerative
CC diseases that affect various mammals. These diseases are caused by
CC abnormally folded prion proteins. BSE can be subdivided into at least
CC three groups: classical, H-type and L-type, with the latter 2
CC collectively referred to as atypical BSE. Susceptibility or resistance
CC to a BSE disease can be influenced by at least 3 factors related to the
CC host prion protein: protein expression levels, number of octapeptide
CC repeats, and specific polymorphisms. In cattle, as in humans, BSEs can
CC occur as infectious, spontaneous and genetic diseases. The heritable
CC variant Lys-211 can be the cause of genetic late onset H-type BSE.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; EU564437; ACE73916.1; -; Genomic_DNA.
DR EMBL; EU564438; ACE73917.1; -; Genomic_DNA.
DR EMBL; EU564439; ACE73918.1; -; Genomic_DNA.
DR EMBL; EU564440; ACE73919.1; -; Genomic_DNA.
DR EMBL; EU564441; ACE73920.1; -; Genomic_DNA.
DR EMBL; EU564442; ACE73921.1; -; Genomic_DNA.
DR EMBL; EU564443; ACE73922.1; -; Genomic_DNA.
DR EMBL; EU564444; ACE73923.1; -; Genomic_DNA.
DR EMBL; EU564445; ACE73924.1; -; Genomic_DNA.
DR EMBL; EU564446; ACE73925.1; -; Genomic_DNA.
DR EMBL; EU564447; ACE73926.1; -; Genomic_DNA.
DR EMBL; EU564448; ACE73927.1; -; Genomic_DNA.
DR EMBL; EU564449; ACE73928.1; -; Genomic_DNA.
DR EMBL; EU564450; ACE73929.1; -; Genomic_DNA.
DR EMBL; EU564507; ACE73986.1; -; Genomic_DNA.
DR EMBL; EU564508; ACE73987.1; -; Genomic_DNA.
DR EMBL; EU564509; ACE73988.1; -; Genomic_DNA.
DR EMBL; EU564510; ACE73989.1; -; Genomic_DNA.
DR EMBL; EU564511; ACE73990.1; -; Genomic_DNA.
DR EMBL; EU564512; ACE73991.1; -; Genomic_DNA.
DR EMBL; EU557971; ACH43175.1; -; Genomic_DNA.
DR EMBL; EU557972; ACH43176.1; -; Genomic_DNA.
DR EMBL; EU809428; ACH43188.1; -; Genomic_DNA.
DR AlphaFoldDB; B5SY89; -.
DR BMRB; B5SY89; -.
DR SMR; B5SY89; -.
DR STRING; 30522.B5SY89; -.
DR Ensembl; ENSBIXT00000025998; ENSBIXP00000036088; ENSBIXG00000019467.
DR Ensembl; ENSBIXT00005000650; ENSBIXP00005032802; ENSBIXG00005013353.
DR GeneTree; ENSGT00510000049083; -.
DR OMA; HNPGYPH; -.
DR Proteomes; UP000314981; Chromosome 13.
DR Proteomes; UP000429181; Chromosome 13.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016234; C:inclusion body; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:1903136; F:cuprous ion binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IEA:Ensembl.
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 1: Evidence at protein level;
KW Amyloid; Cell membrane; Copper; Disease variant; Disulfide bond;
KW Glycoprotein; Golgi apparatus; GPI-anchor; Lipoprotein; Membrane;
KW Metal-binding; Prion; Reference proteome; Repeat; Signal; Zinc.
FT SIGNAL 1..24
FT CHAIN 25..241
FT /note="Major prion protein"
FT /id="PRO_0000410681"
FT PROPEP 242..264
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000410682"
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..94
FT /note="5"
FT REPEAT 95..103
FT /note="6"
FT REGION 25..241
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 25..41
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 28..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..103
FT /note="6 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 72
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 73
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 74
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 80
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 81
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 82
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 88
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 89
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 90
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 96
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 98
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 99
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 241
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 190..225
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT VARIANT 154
FT /note="S -> N"
FT /evidence="ECO:0000269|PubMed:18808703"
FT VARIANT 211
FT /note="E -> K (in H-type BSE)"
FT /evidence="ECO:0000269|PubMed:18698343,
FT ECO:0000269|PubMed:18787697"
SQ SEQUENCE 264 AA; 28614 MW; D6D214038316A231 CRC64;
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW
GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GWGQPHGGGG WGQGGTHGQW NKPSKPKTNM
KHVAGAAAAG AVVGGLGGYM LGSAMSRPLI HFGSDYEDRY YRENMHRYPN QVYYRPVDQY
SNQNNFVHDC VNITVKEHTV TTTTKGENFT ETDIKMMERV VEQMCITQYQ RESQAYYQRG
ASVILFSSPP VILLISFLIF LIVG
