PRIO_MOUSE
ID PRIO_MOUSE Reviewed; 254 AA.
AC P04925;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 224.
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;
GN Name=Prnp; Synonyms=Prn-p, Prp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-108 AND VAL-189.
RC STRAIN=I/LnJ, and NZW/LacJ;
RX PubMed=2890436; DOI=10.1016/0092-8674(87)90134-6;
RA Westaway D., Goodman P.A., Mirenda C.A., McKinley M.P., Carlson G.A.,
RA Prusiner S.B.;
RT "Distinct prion proteins in short and long scrapie incubation period
RT mice.";
RL Cell 51:651-662(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3462700; DOI=10.1073/pnas.83.17.6372;
RA Locht C., Chesebro B., Race R., Keith J.M.;
RT "Molecular cloning and complete sequence of prion protein cDNA from mouse
RT brain infected with the scrapie agent.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:6372-6376(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=NZW/LacJ; TISSUE=Brain;
RX PubMed=9799790; DOI=10.1101/gr.8.10.1022;
RA Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., Acharya C.,
RA Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., Hood L.E.;
RT "Complete genomic sequence and analysis of the prion protein gene region
RT from three mammalian species.";
RL Genome Res. 8:1022-1037(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 PROTEIN SEQUENCE OF N-TERMINUS.
RX PubMed=2894984; DOI=10.1111/j.1432-1033.1988.tb13883.x;
RA Hope J., Multhaup G., Reekie L.J.D., Kimberlin R.H., Beyreuther K.;
RT "Molecular pathology of scrapie-associated fibril protein (PrP) in mouse
RT brain affected by the ME7 strain of scrapie.";
RL Eur. J. Biochem. 172:271-277(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 87-164.
RX PubMed=3923361; DOI=10.1038/315331a0;
RA Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D.,
RA Bergstrom S., Robbins K., Mayer L., Keith J.M., Garon C., Haase A.;
RT "Identification of scrapie prion protein-specific mRNA in scrapie-infected
RT and uninfected brain.";
RL Nature 315:331-333(1985).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=8035877; DOI=10.1038/370295a0;
RA Collinge J., Whittington M.A., Sidle K.C., Smith C.J., Palmer M.S.,
RA Clarke A.R., Jefferys J.G.;
RT "Prion protein is necessary for normal synaptic function.";
RL Nature 370:295-297(1994).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=8637886; DOI=10.1073/pnas.93.6.2403;
RA Lledo P.M., Tremblay P., DeArmond S.J., Prusiner S.B., Nicoll R.A.;
RT "Mice deficient for prion protein exhibit normal neuronal excitability and
RT synaptic transmission in the hippocampus.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:2403-2407(1996).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=9837873; DOI=10.1074/jbc.273.50.33107;
RA Pauly P.C., Harris D.A.;
RT "Copper stimulates endocytosis of the prion protein.";
RL J. Biol. Chem. 273:33107-33110(1998).
RN [10]
RP HYDROXYLATION AT PRO-44.
RX PubMed=11032800; DOI=10.1093/emboj/19.20.5324;
RA Gill A.C., Ritchie M.A., Hunt L.G., Steane S.E., Davies K.G., Bocking S.P.,
RA Rhie A.G.O., Bennett A.D., Hope J.;
RT "Post-translational hydroxylation at the N-terminus of the prion protein
RT reveals presence of PPII structure in vivo.";
RL EMBO J. 19:5324-5331(2000).
RN [11]
RP SUBCELLULAR LOCATION, INTERACTION WITH GRB2; ERI3 AND SYN1, AND MUTAGENESIS
RP OF PRO-101 AND PRO-104.
RX PubMed=11571277; DOI=10.1074/jbc.m103289200;
RA Spielhaupter C., Schaetzl H.M.;
RT "PrPC directly interacts with proteins involved in signaling pathways.";
RL J. Biol. Chem. 276:44604-44612(2001).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=11756421; DOI=10.1074/jbc.m110197200;
RA Lorenz H., Windl O., Kretzschmar H.A.;
RT "Cellular phenotyping of secretory and nuclear prion proteins associated
RT with inherited prion diseases.";
RL J. Biol. Chem. 277:8508-8516(2002).
RN [13]
RP COPPER BINDING, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=12732622; DOI=10.1074/jbc.m300394200;
RA Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.;
RT "Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-
RT nitroso-dependent autocleavage of glypican-1 heparan sulfate.";
RL J. Biol. Chem. 278:38956-38965(2003).
RN [14]
RP DISRUPTION PHENOTYPE.
RX PubMed=15161660; DOI=10.1016/s0002-9440(10)63784-4;
RA Paisley D., Banks S., Selfridge J., McLennan N.F., Ritchie A.M., McEwan C.,
RA Irvine D.S., Saunders P.T., Manson J.C., Melton D.W.;
RT "Male infertility and DNA damage in Doppel knockout and prion
RT protein/Doppel double-knockout mice.";
RL Am. J. Pathol. 164:2279-2288(2004).
RN [15]
RP DISRUPTION PHENOTYPE.
RX PubMed=15007175; DOI=10.1073/pnas.0400131101;
RA Genoud N., Behrens A., Miele G., Robay D., Heppner F.L., Freigang S.,
RA Aguzzi A.;
RT "Disruption of Doppel prevents neurodegeneration in mice with extensive
RT Prnp deletions.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4198-4203(2004).
RN [16]
RP SUBCELLULAR LOCATION, AND COPPER-BINDING.
RX PubMed=16923158; DOI=10.1111/j.1471-4159.2006.03981.x;
RA Cheng F., Lindqvist J., Haigh C.L., Brown D.R., Mani K.;
RT "Copper-dependent co-internalization of the prion protein and glypican-1.";
RL J. Neurochem. 98:1445-1457(2006).
RN [17]
RP DISRUPTION PHENOTYPE, GLYCOSYLATION, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16492732; DOI=10.1073/pnas.0511290103;
RA Steele A.D., Emsley J.G., Ozdinler P.H., Lindquist S., Macklis J.D.;
RT "Prion protein (PrPc) positively regulates neural precursor proliferation
RT during developmental and adult mammalian neurogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:3416-3421(2006).
RN [18]
RP INTERACTION WITH MGRN1.
RX PubMed=19524515; DOI=10.1016/j.cell.2009.03.042;
RA Chakrabarti O., Hegde R.S.;
RT "Functional depletion of mahogunin by cytosolically exposed prion protein
RT contributes to neurodegeneration.";
RL Cell 137:1136-1147(2009).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-196.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [20]
RP DISRUPTION PHENOTYPE, INTERACTION WITH APP, AND FUNCTION.
RX PubMed=19242475; DOI=10.1038/nature07761;
RA Lauren J., Gimbel D.A., Nygaard H.B., Gilbert J.W., Strittmatter S.M.;
RT "Cellular prion protein mediates impairment of synaptic plasticity by
RT amyloid-beta oligomers.";
RL Nature 457:1128-1132(2009).
RN [21]
RP DISRUPTION PHENOTYPE, FUNCTION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=19568430; DOI=10.1371/journal.pone.0006115;
RA Singh A., Kong Q., Luo X., Petersen R.B., Meyerson H., Singh N.;
RT "Prion protein (PrP) knock-out mice show altered iron metabolism: a
RT functional role for PrP in iron uptake and transport.";
RL PLoS ONE 4:E6115-E6115(2009).
RN [22]
RP COPPER-BINDING.
RX PubMed=19381258; DOI=10.1371/journal.ppat.1000390;
RA Stevens D.J., Walter E.D., Rodriguez A., Draper D., Davies P., Brown D.R.,
RA Millhauser G.L.;
RT "Early onset prion disease from octarepeat expansion correlates with copper
RT or zinc binding properties.";
RL PLoS Pathog. 5:E1000390-E1000390(2009).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [24]
RP DISRUPTION PHENOTYPE.
RX PubMed=20098419; DOI=10.1038/nn.2483;
RA Bremer J., Baumann F., Tiberi C., Wessig C., Fischer H., Schwarz P.,
RA Steele A.D., Toyka K.V., Nave K.A., Weis J., Aguzzi A.;
RT "Axonal prion protein is required for peripheral myelin maintenance.";
RL Nat. Neurosci. 13:310-318(2010).
RN [25]
RP STRUCTURE BY NMR OF 120-230.
RX PubMed=8700211; DOI=10.1038/382180a0;
RA Riek R., Hornemann S., Wider G., Bileter M., Glockshuber R., Wuethrich K.;
RT "NMR structure of the mouse prion protein domain PrP(121-321).";
RL Nature 382:180-182(1996).
RN [26]
RP STRUCTURE BY NMR OF 23-231.
RX PubMed=9280298; DOI=10.1016/s0014-5793(97)00920-4;
RA Riek R., Hornemann S., Wider G., Glockshuber R., Wuethrich K.;
RT "NMR characterization of the full-length recombinant murine prion protein,
RT mPrP(23-231).";
RL FEBS Lett. 413:282-288(1997).
RN [27]
RP INTERACTION WITH ADGRG6, AND FUNCTION.
RX PubMed=27501152; DOI=10.1038/nature19312;
RA Kueffer A., Lakkaraju A.K., Mogha A., Petersen S.C., Airich K.,
RA Doucerain C., Marpakwar R., Bakirci P., Senatore A., Monnard A.,
RA Schiavi C., Nuvolone M., Grosshans B., Hornemann S., Bassilana F.,
RA Monk K.R., Aguzzi A.;
RT "The prion protein is an agonistic ligand of the G protein-coupled receptor
RT Adgrg6.";
RL Nature 536:464-468(2016).
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 (PubMed:12732622, PubMed:16492732, PubMed:19242475,
CC PubMed:19568430). {ECO:0000250|UniProtKB:P04156,
CC ECO:0000269|PubMed:12732622, ECO:0000269|PubMed:16492732,
CC ECO:0000269|PubMed:19242475, ECO:0000269|PubMed:19568430}.
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 (PubMed:11571277). Mislocalized cytosolically exposed PrP interacts
CC with MGRN1; this interaction alters MGRN1 subcellular location and
CC causes lysosomal enlargement (By similarity). Interacts with APP.
CC Interacts with KIAA1191 (By similarity). Interacts with ADGRG6
CC (PubMed:27501152). {ECO:0000250|UniProtKB:P04156,
CC ECO:0000269|PubMed:11571277, ECO:0000269|PubMed:27501152}.
CC -!- INTERACTION:
CC P04925; PRO_0000000118 [P12023]: App; NbExp=2; IntAct=EBI-768613, EBI-14022231;
CC P04925; O08532: Cacna2d1; NbExp=3; IntAct=EBI-768613, EBI-770939;
CC P04925; Q60631: Grb2; NbExp=7; IntAct=EBI-768613, EBI-1688;
CC P04925; P04925: Prnp; NbExp=17; IntAct=EBI-768613, EBI-768613;
CC P04925; P04156: PRNP; Xeno; NbExp=3; IntAct=EBI-768613, EBI-977302;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11571277,
CC ECO:0000269|PubMed:9837873}; Lipid-anchor, GPI-anchor. Golgi apparatus
CC {ECO:0000269|PubMed:11756421}. Note=Targeted to lipid rafts via
CC association with the heparan sulfate chains of GPC1. Colocates, in the
CC 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:0000269|PubMed:11571277, ECO:0000269|PubMed:12732622,
CC ECO:0000269|PubMed:16923158, ECO:0000269|PubMed:9837873}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, lung, kidney and
CC heart. Expressed at low levels in the liver and spleen.
CC {ECO:0000269|PubMed:16492732, ECO:0000269|PubMed:19568430}.
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 -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16492732,
CC ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:19568430}.
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 -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice develop chronic
CC demyelinating polyneuropathy after 60 weeks. Mice show abnormally low
CC iron levels throughout the body, and are mildly anemic. Iron
CC accumulates in duodenum enterocytes, suggesting impaired transport from
CC the intestine to the blood. Mice deficient for both Prnd and Prnp have
CC the same phenotype as mice lacking Prnd; they are born at the expected
CC Mendelian rate and appear grossly normal and healthy (PubMed:15161660,
CC PubMed:15007175). Females are fertile, but males deficient for both
CC Prnd and Prnp are sterile, in spite of normal mating behavior
CC (PubMed:15161660, PubMed:15007175). Male sterility is due to impaired
CC acrosome reaction (PubMed:15161660). Mutant sperm are able to fertilize
CC oocytes in vitro, but many of the resulting embryos die before the
CC morula stage (PubMed:15161660). Mutant sperm cells have elevated levels
CC of DNA damage and DNA strand breaks, and this may be the cause for
CC embryonic lethality (PubMed:15161660). Aging mice deficient for both
CC Prnd and Prnp do not display loss of cerebellar Purkinje cells or
CC develop ataxia, and do not develop neurological defects
CC (PubMed:15007175). {ECO:0000269|PubMed:15007175,
CC ECO:0000269|PubMed:15161660, ECO:0000269|PubMed:16492732,
CC ECO:0000269|PubMed:19242475, ECO:0000269|PubMed:19568430,
CC ECO:0000269|PubMed:20098419, ECO:0000269|PubMed:8035877,
CC ECO:0000269|PubMed:8637886}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
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DR EMBL; M18070; AAA39997.1; -; Genomic_DNA.
DR EMBL; M18071; AAA39998.1; -; Genomic_DNA.
DR EMBL; M13685; AAA39996.1; -; mRNA.
DR EMBL; U29186; AAC02804.1; -; Genomic_DNA.
DR EMBL; BC006703; AAH06703.1; -; mRNA.
DR EMBL; M30384; AAA39999.1; -; mRNA.
DR CCDS; CCDS16766.1; -.
DR PIR; A29669; A23544.
DR RefSeq; NP_001265185.1; NM_001278256.1.
DR RefSeq; NP_035300.1; NM_011170.3.
DR PDB; 1AG2; NMR; -; A=123-225.
DR PDB; 1XYX; NMR; -; A=120-231.
DR PDB; 1Y15; NMR; -; A=120-231.
DR PDB; 1Y16; NMR; -; A=120-231.
DR PDB; 2K5O; NMR; -; A=120-231.
DR PDB; 2KFM; NMR; -; A=120-231.
DR PDB; 2KFO; NMR; -; A=120-231.
DR PDB; 2KU5; NMR; -; A=120-231.
DR PDB; 2KU6; NMR; -; A=120-231.
DR PDB; 2L1D; NMR; -; A=120-231.
DR PDB; 2L1E; NMR; -; A=120-231.
DR PDB; 2L1H; NMR; -; A=120-231.
DR PDB; 2L1K; NMR; -; A=120-231.
DR PDB; 2L39; NMR; -; A=118-231.
DR PDB; 2L40; NMR; -; A=120-231.
DR PDB; 3NVG; X-ray; 1.48 A; A=137-142.
DR PDB; 3NVH; X-ray; 1.61 A; A=137-143.
DR PDB; 4H88; X-ray; 1.90 A; A=120-230.
DR PDB; 4J8R; X-ray; 2.30 A; I/J=67-82.
DR PDB; 4MA7; X-ray; 1.97 A; A=116-229.
DR PDB; 4MA8; X-ray; 2.20 A; C=116-229.
DR PDB; 6AQ7; X-ray; 1.83 A; A=127-225.
DR PDB; 6HER; X-ray; 1.20 A; A=117-226.
DR PDB; 6HHD; X-ray; 2.10 A; A=118-225, C=118-224.
DR PDBsum; 1AG2; -.
DR PDBsum; 1XYX; -.
DR PDBsum; 1Y15; -.
DR PDBsum; 1Y16; -.
DR PDBsum; 2K5O; -.
DR PDBsum; 2KFM; -.
DR PDBsum; 2KFO; -.
DR PDBsum; 2KU5; -.
DR PDBsum; 2KU6; -.
DR PDBsum; 2L1D; -.
DR PDBsum; 2L1E; -.
DR PDBsum; 2L1H; -.
DR PDBsum; 2L1K; -.
DR PDBsum; 2L39; -.
DR PDBsum; 2L40; -.
DR PDBsum; 3NVG; -.
DR PDBsum; 3NVH; -.
DR PDBsum; 4H88; -.
DR PDBsum; 4J8R; -.
DR PDBsum; 4MA7; -.
DR PDBsum; 4MA8; -.
DR PDBsum; 6AQ7; -.
DR PDBsum; 6HER; -.
DR PDBsum; 6HHD; -.
DR AlphaFoldDB; P04925; -.
DR BMRB; P04925; -.
DR SASBDB; P04925; -.
DR SMR; P04925; -.
DR BioGRID; 202389; 61.
DR CORUM; P04925; -.
DR DIP; DIP-4N; -.
DR IntAct; P04925; 15.
DR MINT; P04925; -.
DR STRING; 10090.ENSMUSP00000088833; -.
DR BindingDB; P04925; -.
DR ChEMBL; CHEMBL3698; -.
DR GlyConnect; 2499; 3 N-Linked glycans (1 site).
DR GlyGen; P04925; 2 sites, 41 N-linked glycans (2 sites).
DR iPTMnet; P04925; -.
DR MetOSite; P04925; -.
DR PhosphoSitePlus; P04925; -.
DR SwissPalm; P04925; -.
DR EPD; P04925; -.
DR PaxDb; P04925; -.
DR PeptideAtlas; P04925; -.
DR PRIDE; P04925; -.
DR ProteomicsDB; 289840; -.
DR ABCD; P04925; 25 sequenced antibodies.
DR Antibodypedia; 3351; 656 antibodies from 47 providers.
DR DNASU; 19122; -.
DR Ensembl; ENSMUST00000091288; ENSMUSP00000088833; ENSMUSG00000079037.
DR GeneID; 19122; -.
DR KEGG; mmu:19122; -.
DR UCSC; uc008mly.3; mouse.
DR CTD; 5621; -.
DR MGI; MGI:97769; Prnp.
DR VEuPathDB; HostDB:ENSMUSG00000079037; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR GeneTree; ENSGT00510000049083; -.
DR HOGENOM; CLU_094631_0_0_1; -.
DR InParanoid; P04925; -.
DR OMA; HNPGYPH; -.
DR OrthoDB; 1403854at2759; -.
DR PhylomeDB; P04925; -.
DR TreeFam; TF105188; -.
DR Reactome; R-MMU-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR BioGRID-ORCS; 19122; 0 hits in 71 CRISPR screens.
DR EvolutionaryTrace; P04925; -.
DR PRO; PR:P04925; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P04925; protein.
DR Bgee; ENSMUSG00000079037; Expressed in bed nucleus of stria terminalis and 293 other tissues.
DR ExpressionAtlas; P04925; baseline and differential.
DR Genevisible; P04925; MM.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016234; C:inclusion body; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; IDA:CACAO.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IDA:ARUK-UCL.
DR GO; GO:0043008; F:ATP-dependent protein binding; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; IDA:MGI.
DR GO; GO:1903135; F:cupric ion binding; IMP:CAFA.
DR GO; GO:1903136; F:cuprous ion binding; ISO:MGI.
DR GO; GO:0005539; F:glycosaminoglycan binding; IDA:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005521; F:lamin binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISO:MGI.
DR GO; GO:0002020; F:protease binding; IPI:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; IMP:ARUK-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0015631; F:tubulin binding; ISO:MGI.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IPI:ARUK-UCL.
DR GO; GO:0032147; P:activation of protein kinase activity; IGI:ARUK-UCL.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IGI:ARUK-UCL.
DR GO; GO:0006878; P:cellular copper ion homeostasis; TAS:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0071280; P:cellular response to copper ion; ISO:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0007611; P:learning or memory; IGI:ARUK-UCL.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IMP:BHF-UCL.
DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; IGI:ARUK-UCL.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IGI:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IGI:MGI.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IMP:BHF-UCL.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:MGI.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; IGI:ARUK-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:BHF-UCL.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:BHF-UCL.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:BHF-UCL.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:1990535; P:neuron projection maintenance; IGI:ARUK-UCL.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; IGI:ARUK-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; IGI:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:ARUK-UCL.
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; IGI:ARUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; ISO:MGI.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IGI:ARUK-UCL.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IGI:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:1904645; P:response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0046686; P:response to cadmium ion; ISO:MGI.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IDA:MGI.
DR DisProt; DP00265; -.
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 3D-structure; Amyloid; Cell membrane; Copper; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor; Hydroxylation;
KW Lipoprotein; Membrane; Metal-binding; Prion; Reference proteome; Repeat;
KW Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:2894984"
FT CHAIN 23..230
FT /note="Major prion protein"
FT /id="PRO_0000025697"
FT PROPEP 231..254
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT /id="PRO_0000025698"
FT REPEAT 51..58
FT /note="1"
FT REPEAT 59..66
FT /note="2"
FT REPEAT 67..74
FT /note="3"
FT REPEAT 75..82
FT /note="4"
FT REPEAT 83..90
FT /note="5"
FT REGION 23..231
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000269|PubMed:11571277"
FT REGION 23..38
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000269|PubMed:27501152"
FT REGION 25..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..90
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 60
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="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 68
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="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 76
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="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 84
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
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 MOD_RES 44
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:11032800"
FT LIPID 230
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 178..213
FT VARIANT 108
FT /note="L -> F (linked to long incubation time)"
FT VARIANT 189
FT /note="T -> V (linked to long incubation time; requires 2
FT nucleotide substitutions)"
FT MUTAGEN 101
FT /note="P->L: No effect on interaction with GRB2."
FT /evidence="ECO:0000269|PubMed:11571277"
FT MUTAGEN 104
FT /note="P->L: No effect on interaction with GRB2."
FT /evidence="ECO:0000269|PubMed:11571277"
FT CONFLICT 133
FT /note="M -> V (in Ref. 2; AAA39996 and 6; AAA39999)"
FT /evidence="ECO:0000305"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:6HER"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:6HER"
FT HELIX 143..152
FT /evidence="ECO:0007829|PDB:6HER"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:6HER"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2L39"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:6HER"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:6HER"
FT HELIX 171..188
FT /evidence="ECO:0007829|PDB:6HER"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:6AQ7"
FT HELIX 199..225
FT /evidence="ECO:0007829|PDB:6HER"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:2KU5"
SQ SEQUENCE 254 AA; 27977 MW; D5331E6321826CC0 CRC64;
MANLGYWLLA LFVTMWTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGTWGQPH
GGGWGQPHGG SWGQPHGGSW GQPHGGGWGQ GGGTHNQWNK PSKPKTNLKH VAGAAAAGAV
VGGLGGYMLG SAMSRPMIHF GNDWEDRYYR ENMYRYPNQV YYRPVDQYSN QNNFVHDCVN
ITIKQHTVTT TTKGENFTET DVKMMERVVE QMCVTQYQKE SQAYYDGRRS SSTVLFSSPP
VILLISFLIF LIVG
