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 27-MAR-2024, entry version 233. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7QIG; EM; 2.70 A; A/B/C=94-225. DR PDB; 7RVD; EM; 1.00 A; A=167-175. DR PDB; 7TD6; EM; 3.00 A; 1/A/B/C/D=1-254. DR PDB; 8A00; EM; 2.60 A; A/B/C=94-229. DR PDB; 8DJA; EM; 3.92 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=23-143. DR PDB; 8EFU; EM; 3.20 A; A/B/C/D/E=1-231. 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 PDBsum; 7QIG; -. DR PDBsum; 7RVD; -. DR PDBsum; 7TD6; -. DR PDBsum; 8A00; -. DR PDBsum; 8DJA; -. DR PDBsum; 8EFU; -. DR AlphaFoldDB; P04925; -. DR BMRB; P04925; -. DR EMDB; EMD-13989; -. DR EMDB; EMD-15043; -. DR EMDB; EMD-25824; -. DR EMDB; EMD-27458; -. DR EMDB; EMD-28089; -. DR SASBDB; P04925; -. DR SMR; P04925; -. DR BioGRID; 202389; 65. 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 GlyCosmos; P04925; 2 sites, 41 glycans. DR GlyGen; P04925; 3 sites, 41 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P04925; -. DR MetOSite; P04925; -. DR PhosphoSitePlus; P04925; -. DR SwissPalm; P04925; -. DR EPD; P04925; -. DR PaxDb; 10090-ENSMUSP00000088833; -. DR PeptideAtlas; P04925; -. DR ProteomicsDB; 289840; -. DR Pumba; P04925; -. DR ABCD; P04925; 25 sequenced antibodies. DR Antibodypedia; 3351; 919 antibodies from 47 providers. DR DNASU; 19122; -. DR Ensembl; ENSMUST00000091288.13; ENSMUSP00000088833.7; ENSMUSG00000079037.10. DR GeneID; 19122; -. DR KEGG; mmu:19122; -. DR UCSC; uc008mly.3; mouse. DR AGR; MGI:97769; -. 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; QMCTTQY; -. DR OrthoDB; 5265139at2759; -. 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; 1 hit in 76 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 296 other cell types or tissues. DR ExpressionAtlas; P04925; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. 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:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISO:MGI. DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW. 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: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:0046872; F:metal ion binding; IDA:DisProt. DR GO; GO:0008017; F:microtubule binding; ISO:MGI. DR GO; GO:0060090; F:molecular adaptor activity; IPI:DisProt. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:DisProt. DR GO; GO:0140677; F:molecular function activator activity; IEP:DisProt. DR GO; GO:0002020; F:protease binding; IPI:ARUK-UCL. DR GO; GO:0140311; F:protein sequestering activity; IDA:DisProt. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:MGI. 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: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:0006878; P:intracellular copper ion homeostasis; TAS: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: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: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:0032689; P:negative regulation of type II interferon production; 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:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI. 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: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: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; Prion/Doppel protein, beta-ribbon domain; 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 PANTHER; PTHR15506; DOPPEL PRION; 1. DR PANTHER; PTHR15506:SF2; MAJOR PRION PROTEIN; 1. DR Pfam; PF00377; Prion; 1. DR Pfam; PF11587; Prion_bPrPp; 1. DR PRINTS; PR00341; PRION. DR SMART; SM00157; PRP; 1. DR SUPFAM; SSF54098; Prion-like; 1. DR PROSITE; PS00291; PRION_1; 1. DR PROSITE; PS00706; PRION_2; 1. DR Genevisible; P04925; MM. 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 95..99 FT /evidence="ECO:0007829|PDB:8A00" FT STRAND 106..112 FT /evidence="ECO:0007829|PDB:8A00" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:8A00" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:6HER" FT STRAND 124..128 FT /evidence="ECO:0007829|PDB:6HER" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:8A00" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:7QIG" FT HELIX 143..152 FT /evidence="ECO:0007829|PDB:6HER" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:6HER" FT STRAND 158..162 FT /evidence="ECO:0007829|PDB:8A00" 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 //