PRIO_RAT
ID PRIO_RAT Reviewed; 254 AA.
AC P13852; Q549H6;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=Prnp; Synonyms=Prn, Prp;
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 [GENOMIC DNA].
RC STRAIN=SJ/D, and Zitter; TISSUE=Liver;
RX PubMed=7909925; DOI=10.1016/0304-3940(94)90478-2;
RA Gomi H., Ikeda T., Kunieda T., Itohara S., Prusiner S.B., Yamanouchi K.;
RT "Prion protein (PrP) is not involved in the pathogenesis of spongiform
RT encephalopathy in zitter rats.";
RL Neurosci. Lett. 166:171-174(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8879116; DOI=10.1007/bf00369996;
RA Saeki K., Matsumoto Y., Hirota Y., Matsumoto Y., Onodera T.;
RT "Three-exon structure of the gene encoding the rat prion protein and its
RT expression in tissues.";
RL Virus Genes 12:15-20(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=10373359; DOI=10.1006/jmbi.1999.2831;
RA Wopfner F., Weidenhofer G., Schneider R., von Brunn A., Gilch S.,
RA Schwarz T.F., Werner T., Schatzl H.M.;
RT "Analysis of 27 mammalian and 9 avian PrPs reveals high conservation of
RT flexible regions of the prion protein.";
RL J. Mol. Biol. 289:1163-1178(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 29-254.
RX PubMed=2889848;
RA Liao Y.-C., Tokes Z., Lim E., Lackey A., Woo C.H., Button J.D.,
RA Clawson G.A.;
RT "Cloning of rat 'prion-related protein' cDNA.";
RL Lab. Invest. 57:370-374(1987).
RN [6]
RP PROTEIN SEQUENCE OF 209-229, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U., Lubec S.;
RL Submitted (SEP-2007) to UniProtKB.
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=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; S69654; AAB30728.2; -; Genomic_DNA.
DR EMBL; D50093; BAA08790.1; -; Genomic_DNA.
DR EMBL; AF117322; AAD19993.1; -; Genomic_DNA.
DR EMBL; BC072692; AAH72692.1; -; mRNA.
DR EMBL; M20313; AAA41947.1; -; mRNA.
DR PIR; A53892; A53892.
DR RefSeq; NP_036763.1; NM_012631.2.
DR RefSeq; XP_006235124.1; XM_006235062.3.
DR AlphaFoldDB; P13852; -.
DR BMRB; P13852; -.
DR SMR; P13852; -.
DR BioGRID; 246818; 2.
DR STRING; 10116.ENSRNOP00000028881; -.
DR GlyGen; P13852; 2 sites.
DR iPTMnet; P13852; -.
DR PhosphoSitePlus; P13852; -.
DR jPOST; P13852; -.
DR PaxDb; P13852; -.
DR PRIDE; P13852; -.
DR Ensembl; ENSRNOT00000104185; ENSRNOP00000093351; ENSRNOG00000021259.
DR Ensembl; ENSRNOT00000106614; ENSRNOP00000093957; ENSRNOG00000021259.
DR Ensembl; ENSRNOT00000113525; ENSRNOP00000085462; ENSRNOG00000021259.
DR Ensembl; ENSRNOT00000117610; ENSRNOP00000096232; ENSRNOG00000021259.
DR GeneID; 24686; -.
DR KEGG; rno:24686; -.
DR UCSC; RGD:3410; rat.
DR CTD; 5621; -.
DR RGD; 3410; Prnp.
DR VEuPathDB; HostDB:ENSRNOG00000070982; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR GeneTree; ENSGT00510000049083; -.
DR HOGENOM; CLU_094631_0_0_1; -.
DR InParanoid; P13852; -.
DR OMA; HNPGYPH; -.
DR OrthoDB; 1403854at2759; -.
DR PhylomeDB; P13852; -.
DR TreeFam; TF105188; -.
DR Reactome; R-RNO-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR PRO; PR:P13852; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000021259; Expressed in Ammon's horn and 19 other tissues.
DR Genevisible; P13852; RN.
DR GO; GO:0046658; C:anchored component of plasma membrane; TAS:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0016234; C:inclusion body; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:ARUK-UCL.
DR GO; GO:0043195; C:terminal bouton; ISO:RGD.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; ISO:RGD.
DR GO; GO:0043008; F:ATP-dependent protein binding; IPI:RGD.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IPI:RGD.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:1903135; F:cupric ion binding; ISO:RGD.
DR GO; GO:1903136; F:cuprous ion binding; ISO:RGD.
DR GO; GO:0005539; F:glycosaminoglycan binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005521; F:lamin binding; IPI:RGD.
DR GO; GO:0008017; F:microtubule binding; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0038023; F:signaling receptor activity; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0015631; F:tubulin binding; ISO:RGD.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IPI:ARUK-UCL.
DR GO; GO:0032147; P:activation of protein kinase activity; ISO:RGD.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD.
DR GO; GO:0071280; P:cellular response to copper ion; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IMP:RGD.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:ARUK-UCL.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IDA:ARUK-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:RGD.
DR GO; GO:1990535; P:neuron projection maintenance; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISO:RGD.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; ISO:RGD.
DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; ISO:RGD.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; ISO:RGD.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0032880; P:regulation of protein localization; ISO:RGD.
DR GO; GO:1904645; P:response to amyloid-beta; ISO:RGD.
DR GO; GO:0046686; P:response to cadmium ion; IDA:RGD.
DR GO; GO:0046688; P:response to copper ion; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Golgi apparatus; GPI-anchor; Lipoprotein; Membrane;
KW Metal-binding; Prion; Reference proteome; Repeat; Signal; Zinc.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..231
FT /note="Major prion protein"
FT /id="PRO_0000025723"
FT PROPEP 232..254
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000025724"
FT REPEAT 51..59
FT /note="1"
FT REPEAT 60..67
FT /note="2"
FT REPEAT 68..75
FT /note="3"
FT REPEAT 76..83
FT /note="4"
FT REPEAT 84..91
FT /note="5"
FT REGION 23..231
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 23..38
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 24..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..91
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT COMPBIAS 36..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..105
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 61
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 62
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 63
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 69
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 70
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 71
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 77
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 78
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 79
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 85
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 86
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 87
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 231
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 179..214
FT /evidence="ECO:0000250|UniProtKB:P04273"
SQ SEQUENCE 254 AA; 27804 MW; 28F424D13BEFA2C6 CRC64;
MANLGYWLLA LFVTTCTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQSGGTWGQP
HGGGWGQPHG GGWGQPHGGG WGQPHGGGWS QGGGTHNQWN KPSKPKTNLK HVAGAAAAGA
VVGGLGGYML GSAMSRPMLH FGNDWEDRYY RENMYRYPNQ VYYRPVDQYS NQNNFVHDCV
NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCVTQYQK ESQAYYDGRR SSAVLFSSPP
VILLISFLIF LIVG
