ID PRIO_HUMAN Reviewed; 253 AA. AC P04156; O60489; P78446; Q15216; Q15221; Q27H91; Q5QPB4; Q8TBG0; AC Q96E70; Q9UP19; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 28-NOV-2012, entry version 172. DE RecName: Full=Major prion protein; DE Short=PrP; DE AltName: Full=ASCR; DE AltName: Full=PrP27-30; DE AltName: Full=PrP33-35C; DE AltName: CD_antigen=CD230; DE Flags: Precursor; GN Name=PRNP; Synonyms=PRIP, PRP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=86300093; PubMed=3755672; RA Kretzschmar H.A., Stowring L.E., Westaway D., Stubblebine W.H., RA Prusiner S.B., Dearmond S.J.; RT "Molecular cloning of a human prion protein cDNA."; RL DNA 5:315-324(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT 56-GLY--GLY-63 DEL. RC TISSUE=Brain; RX MEDLINE=91328137; PubMed=1678248; RA Puckett C., Concannon P., Casey C., Hood L.E.; RT "Genomic structure of the human prion protein gene."; RL Am. J. Hum. Genet. 49:320-329(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=99018115; PubMed=9799790; RA Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., RA Acharya C., Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., RA Hood L.E.; RT "Complete genomic sequence and analysis of the prion protein gene RT region from three mammalian species."; RL Genome Res. 8:1022-1037(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GSD ARG-187. RC TISSUE=Blood; RX MEDLINE=20049886; PubMed=10581485; RX DOI=10.1002/(SICI)1096-8628(19991215)88:6<653::AID-AJMG14>3.0.CO;2-E; RA Cervenakova L., Buetefisch C., Lee H.S., Taller I., Stone G., RA Gibbs C.J. Jr., Brown P., Hallett M., Goldfarb L.G.; RT "Novel PRNP sequence variant associated with familial RT encephalopathy."; RL Am. J. Med. Genet. 88:653-656(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Prostate; RA Hryb D.J., Reynolds T.A., Nakhla A.M., Kahn S.M., Khan S.M., RA Romas N.A., Rosner W.; RT "Cloning of human prostate prion protein cDNA."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Zhang J., Liu Y., Chen H., Jiang H., Lu W., Zhu X., Xie Q., Cai X., RA Liu X.; RT "Analysis and comparison of several mammalian prion protein genes RT Prnp."; RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=21638749; PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Ovary; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-253. RX MEDLINE=86261778; PubMed=3014653; DOI=10.1126/science.3014653; RA Liao Y.-C.J., Lebo R.V., Clawson G.A., Smuckler E.A.; RT "Human prion protein cDNA: molecular cloning, chromosomal mapping, and RT biological implications."; RL Science 233:364-367(1986). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-232, AND VARIANT 56-GLY--GLY-63 RP DEL. RC TISSUE=Brain; RX MEDLINE=93250789; PubMed=1363802; DOI=10.1093/hmg/1.6.443; RA Diedrich J.F., Knopman D.S., List J.F., Olson K., Frey W.H., RA Emory C.R., Sung J.H., Haase A.T.; RT "Deletion in the prion protein gene in a demented patient."; RL Hum. Mol. Genet. 1:443-444(1992). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-253, AND VARIANT RP SCHIZOAFFECTIVE DISORDER SER-171. RX MEDLINE=98044028; PubMed=9384372; DOI=10.1038/36757; RA Samaia H.B., Mari J.J., Vallada H.P., Moura R.P., Simpson A.J.G., RA Brentani R.R.; RT "A prion-linked psychiatric disorder."; RL Nature 390:241-241(1997). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-85, AND VARIANT 56-GLY--GLY-63 RP DEL. RX MEDLINE=96090306; PubMed=7485229; DOI=10.1002/ajmg.1320600104; RA Perry R.T., Go R.C., Harrell L.E., Acton R.T.; RT "SSCP analysis and sequencing of the human prion protein gene (PRNP) RT detects two different 24 bp deletions in an atypical Alzheimer's RT disease family."; RL Am. J. Med. Genet. 60:12-18(1995). RN [13] RP PROTEIN SEQUENCE OF 58-85 AND 111-150. RX MEDLINE=91160504; PubMed=1672107; RA Tagliavini F., Prelli F., Ghiso J., Bugiani O., Serban D., RA Prusiner S.B., Farlow M.R., Ghetti B., Frangione B.; RT "Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana RT kindred) is an 11 kd fragment of prion protein with an N-terminal RT glycine at codon 58."; RL EMBO J. 10:513-519(1991). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-91. RX MEDLINE=92073400; PubMed=1683708; DOI=10.1073/pnas.88.23.10926; RA Goldfarb L.G., Brown P., McCombie W.R., Goldgaber D., Swergold G.D., RA Wills P.R., Cervenakova L., Baron H., Gibbs C.J. Jr., Gajdusek D.C.; RT "Transmissible familial Creutzfeldt-Jakob disease associated with RT five, seven, and eight extra octapeptide coding repeats in the PRNP RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 88:10926-10930(1991). RN [15] RP COPPER-BINDING, 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 RT S-nitroso-dependent autocleavage of glypican-1 heparan sulfate."; RL J. Biol. Chem. 278:38956-38965(2003). RN [16] RP COPPER-BINDING. RX PubMed=16144413; DOI=10.1021/ja053254z; RA Chattopadhyay M., Walter E.D., Newell D.J., Jackson P.J., RA Aronoff-Spencer E., Peisach J., Gerfen G.J., Bennett B., RA Antholine W.E., Millhauser G.L.; RT "The octarepeat domain of the prion protein binds Cu(II) with three RT distinct coordination modes at pH 7.4."; RL J. Am. Chem. Soc. 127:12647-12656(2005). RN [17] RP COPPER AND ZINC BINDING. RX PubMed=18034490; DOI=10.1021/ja077146j; RA Walter E.D., Stevens D.J., Visconte M.P., Millhauser G.L.; RT "The prion protein is a combined zinc and copper binding protein: Zn2+ RT alters the distribution of Cu2+ coordination modes."; RL J. Am. Chem. Soc. 129:15440-15441(2007). RN [18] RP ALTERNATIVE INITIATION (ISOFORM 2), SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF MET-1 AND MET-8. RX PubMed=19059915; DOI=10.1074/jbc.M804051200; RA Juanes M.E., Elvira G., Garcia-Grande A., Calero M., Gasset M.; RT "Biosynthesis of prion protein nucleocytoplasmic isoforms by RT alternative initiation of translation."; RL J. Biol. Chem. 284:2787-2794(2009). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197, AND MASS RP SPECTROMETRY. RC TISSUE=Leukemic T-cell; 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- RT linked cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [20] RP FUNCTION, SUBCELLULAR LOCATION, AND DISEASE ASSOCIATION. RX PubMed=19936054; DOI=10.1371/journal.ppat.1000666; RA Taylor D.R., Whitehouse I.J., Hooper N.M.; RT "Glypican-1 mediates both prion protein lipid raft association and RT disease isoform formation."; RL PLoS Pathog. 5:E1000666-E1000666(2009). RN [21] 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., RA Brown D.R., Millhauser G.L.; RT "Early onset prion disease from octarepeat expansion correlates with RT copper or zinc binding properties."; RL PLoS Pathog. 5:E1000390-E1000390(2009). RN [22] RP SUBUNIT, AND DOMAIN. RX PubMed=20375014; DOI=10.1074/jbc.M110.111815; RA Adrover M., Pauwels K., Prigent S., de Chiara C., Xu Z., Chapuis C., RA Pastore A., Rezaei H.; RT "Prion fibrillization is mediated by a native structural element that RT comprises helices H2 and H3."; RL J. Biol. Chem. 285:21004-21012(2010). RN [23] RP COPPER-BINDING, CIRCULAR DICHROISM, DOMAIN, FUNCTION, AND SUBUNIT. RX PubMed=20564047; DOI=10.1002/jcb.22743; RA Wu D., Zhang W., Luo Q., Luo K., Huang L., Wang W., Huang T., Chen R., RA Lin Y., Pang D., Xiao G.; RT "Copper (II) promotes the formation of soluble neurotoxic PrP RT oligomers in acidic environment."; RL J. Cell. Biochem. 111:627-633(2010). RN [24] RP INTERACTION WITH KIAA1191. RX PubMed=21153684; DOI=10.1007/s11010-010-0690-4; RA Mishra M., Inoue N., Heese K.; RT "Characterizing the novel protein p33MONOX."; RL Mol. Cell. Biochem. 350:127-134(2011). RN [25] RP STRUCTURE BY NMR OF 90-231 OF MUTANT LYS-200. RX PubMed=10954699; DOI=10.1074/jbc.C000483200; RA Zhang Y., Swietnicki W., Zagorski M.G., Surewicz W.K., RA Soennichsen F.D.; RT "Solution structure of the E200K variant of human prion protein. RT Implications for the mechanism of pathogenesis in familial prion RT diseases."; RL J. Biol. Chem. 275:33650-33654(2000). RN [26] RP STRUCTURE BY NMR OF 23-230. RX MEDLINE=20087216; PubMed=10618385; DOI=10.1073/pnas.97.1.145; RA Zahn R., Liu A., Luhrs T., Riek R., von Schroetter C., RA Lopez Garcia F., Billeter M., Calzolai L., Wider G., Wuethrich K.; RT "NMR solution structure of the human prion protein."; RL Proc. Natl. Acad. Sci. U.S.A. 97:145-150(2000). RN [27] RP STRUCTURE BY NMR OF 118-221. RX MEDLINE=20359708; PubMed=10900000; DOI=10.1073/pnas.97.15.8340; RA Calzolai L., Lysek D.A., Guntert P., von Schroetter C., Riek R., RA Zahn R., Wuethrich K.; RT "NMR structures of three single-residue variants of the human prion RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 97:8340-8345(2000). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 119-226, DOMAIN, AND SUBUNIT. RX PubMed=11524679; DOI=10.1038/nsb0901-770; RA Knaus K.J., Morillas M., Swietnicki W., Malone M., Surewicz W.K., RA Yee V.C.; RT "Crystal structure of the human prion protein reveals a mechanism for RT oligomerization."; RL Nat. Struct. Biol. 8:770-774(2001). RN [29] RP X-RAY CRYSTALLOGRAPHY (0.75 ANGSTROMS) OF 61-65 IN COMPLEX WITH COPPER RP ION, DOMAIN, AND SUBUNIT. RX PubMed=11900542; DOI=10.1021/bi011922x; RA Burns C.S., Aronoff-Spencer E., Dunham C.M., Lario P., Avdievich N.I., RA Antholine W.E., Olmstead M.M., Vrielink A., Gerfen G.J., Peisach J., RA Scott W.G., Millhauser G.L.; RT "Molecular features of the copper binding sites in the octarepeat RT domain of the prion protein."; RL Biochemistry 41:3991-4001(2002). RN [30] RP STRUCTURE BY NMR OF 61-68, DISULFIDE BOND, AND SUBUNIT. RX PubMed=14623188; DOI=10.1016/j.jmb.2003.09.048; RA Zahn R.; RT "The octapeptide repeats in mammalian prion protein constitute a pH- RT dependent folding and aggregation site."; RL J. Mol. Biol. 334:477-488(2003). RN [31] RP REVIEW ON VARIANTS. RX MEDLINE=93372867; PubMed=8364585; DOI=10.1002/humu.1380020303; RA Palmer M.S., Collinge J.; RT "Mutations and polymorphisms in the prion protein gene."; RL Hum. Mutat. 2:168-173(1993). RN [32] RP REVIEW ON VARIANTS. RX MEDLINE=94029646; PubMed=8105771; RA Prusiner S.B.; RT "Genetic and infectious prion diseases."; RL Arch. Neurol. 50:1129-1153(1993). RN [33] RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 170-175, SUBUNIT, AND RP DOMAIN. RX PubMed=17468747; DOI=10.1038/nature05695; RA Sawaya M.R., Sambashivan S., Nelson R., Ivanova M.I., Sievers S.A., RA Apostol M.I., Thompson M.J., Balbirnie M., Wiltzius J.J., RA McFarlane H.T., Madsen A.O., Riekel C., Eisenberg D.; RT "Atomic structures of amyloid cross-beta spines reveal varied steric RT zippers."; RL Nature 447:453-457(2007). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 119-231 IN COMPLEX WITH FAB RP FRAGMENT OF MONOCLONAL ANTIBODY ICSM 18, AND SUBUNIT. RX PubMed=19204296; DOI=10.1073/pnas.0809170106; RA Antonyuk S.V., Trevitt C.R., Strange R.W., Jackson G.S., Sangar D., RA Batchelor M., Cooper S., Fraser C., Jones S., Georgiou T., RA Khalili-Shirazi A., Clarke A.R., Hasnain S.S., Collinge J.; RT "Crystal structure of human prion protein bound to a therapeutic RT antibody."; RL Proc. Natl. Acad. Sci. U.S.A. 106:2554-2558(2009). RN [35] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 125-227 OF VARIANT VAL-129; RP VARIANT FFI/CJD ASN-178 AND VARIANT GSD SER-198, SUBUNIT, AND DOMAIN. RX PubMed=19927125; DOI=10.1038/emboj.2009.333; RA Lee S., Antony L., Hartmann R., Knaus K.J., Surewicz K., RA Surewicz W.K., Yee V.C.; RT "Conformational diversity in prion protein variants influences RT intermolecular beta-sheet formation."; RL EMBO J. 29:251-262(2010). RN [36] RP VARIANT GSD LEU-102. RX MEDLINE=89159432; PubMed=2564168; DOI=10.1038/338342a0; RA Hsiao K., Baker H.F., Crow T.J., Poulter M., Owen F., RA Terwilliger J.D., Westaway D., Ott J., Pursiner S.B.; RT "Linkage of a prion protein missense variant to Gerstmann-Straussler RT syndrome."; RL Nature 338:342-345(1989). RN [37] RP VARIANTS LEU-102; VAL-117 AND VAL-129. RX MEDLINE=89392018; PubMed=2783132; DOI=10.1016/0006-291X(89)92317-6; RA Doh-Ura K., Tateishi J., Sasaki H., Kitamoto T., Sakaki Y.; RT "Pro-->Leu change at position 102 of prion protein is the most common RT but not the sole mutation related to Gerstmann-Straussler syndrome."; RL Biochem. Biophys. Res. Commun. 163:974-979(1989). RN [38] RP VARIANT FFI ASN-178. RX MEDLINE=92195483; PubMed=1347910; RA Medori R., Montagna P., Tritschler H.J., Leblanc A., Cortelli P., RA Tinuper P., Lugaresi E., Gambetti P.; RT "Fatal familial insomnia: a second kindred with mutation of prion RT protein gene at codon 178."; RL Neurology 42:669-670(1992). RN [39] RP VARIANT CJD ASN-178. RX MEDLINE=91124933; PubMed=1671440; DOI=10.1016/0140-6736(91)91198-4; RA Goldfarb L.G., Haltia M., Brown P., Nieto A., Kovanen J., RA McCombie W.R., Trapp S., Gajdusek D.C.; RT "New mutation in scrapie amyloid precursor gene (at codon 178) in RT Finnish Creutzfeldt-Jakob kindred."; RL Lancet 337:425-425(1991). RN [40] RP VARIANT CJD LYS-200. RX MEDLINE=90355709; PubMed=1975028; DOI=10.1016/0140-6736(90)92073-Q; RA Goldfarb L., Mitrova E., Brown P., Toh B.K., Gajdusek D.C.; RT "Mutation in codon 200 of scrapie amyloid protein gene in two clusters RT of Creutzfeldt-Jakob disease in Slovakia."; RL Lancet 336:514-515(1990). RN [41] RP VARIANT GSD ARG-217. RX MEDLINE=93250977; PubMed=1363810; DOI=10.1038/ng0492-68; RA Hsiao K., Dlouhy S.R., Farlow M.R., Cass C., da Costa M., RA Conneally P.M., Hodes M.E., Ghetti B., Prusiner S.B.; RT "Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with RT neurofibrillary tangles."; RL Nat. Genet. 1:68-71(1992). RN [42] RP VARIANTS CJD ILE-180 AND ARG-232. RX MEDLINE=93213314; PubMed=8461023; DOI=10.1006/bbrc.1993.1275; RA Kitamoto T., Ohta M., Doh-Ura K., Hitoshi S., Terao Y., Tateishi J.; RT "Novel missense variants of prion protein in Creutzfeldt-Jakob disease RT or Gerstmann-Straussler syndrome."; RL Biochem. Biophys. Res. Commun. 191:709-714(1993). RN [43] RP VARIANT CJD ILE-210. RX MEDLINE=94071412; PubMed=7902693; DOI=10.1002/ana.410340608; RA Pocchiari M., Salvatore M., Cutruzzola F., Genuardi M., RA Allcatelli C.T., Masullo C., Macchi G., Alema G., Galgani S., Xi Y.G., RA Petraroli R., Silvestrini M.C., Brunori M.; RT "A new point mutation of the prion protein gene in Creutzfeldt-Jakob RT disease."; RL Ann. Neurol. 34:802-807(1993). RN [44] RP VARIANT GSD LEU-105. RX MEDLINE=94077414; PubMed=7902972; RA Yamada M., Itoh Y., Fujigasaki H., Naruse S., Kaneko K., Kitamoto T., RA Tateishi J., Otomo E., Hayakawa M., Tanaka J., Matsushita M., RA Miyatake T.; RT "A missense mutation at codon 105 with codon 129 polymorphism of the RT prion protein gene in a new variant of Gerstmann-Straussler-Scheinker RT disease."; RL Neurology 43:2723-2724(1993). RN [45] RP VARIANT GSD LEU-105. RX MEDLINE=95213742; PubMed=7699395; DOI=10.1016/0022-510X(94)90138-4; RA Itoh Y., Yamada M., Hayakawa M., Shozawa T., Tanaka J., Matsushita M., RA Kitamoto T., Tateishi J., Otomo E.; RT "A variant of Gerstmann-Straussler-Scheinker disease carrying codon RT 105 mutation with codon 129 polymorphism of the prion protein gene: a RT clinicopathological study."; RL J. Neurol. Sci. 127:77-86(1994). RN [46] RP VARIANT CJD LYS-200. RX MEDLINE=94142912; PubMed=7906019; RA Inoue I., Kitamoto T., Doh-Ura K., Shii H., Goto I., Tateishi J.; RT "Japanese family with Creutzfeldt-Jakob disease with codon 200 point RT mutation of the prion protein gene."; RL Neurology 44:299-301(1994). RN [47] RP VARIANT CJD LYS-200. RX MEDLINE=94316708; PubMed=7913755; RA Gabizon R., Rosenman H., Meiner Z., Kahana I., Kahana E., Shugart Y., RA Ott J., Prusiner S.B.; RT "Mutation in codon 200 and polymorphism in codon 129 of the prion RT protein gene in Libyan Jews with Creutzfeldt-Jakob disease."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 343:385-390(1994). RN [48] RP VARIANT GSD LEU-102. RX MEDLINE=95303274; PubMed=7783876; RA Young K., Jones C.K., Piccardo P., Lazzarini A., Golbe L.I., RA Zimmerman T.R., Dickson D.W., McLachlan D.C., St George-Hyslop P.H., RA Lennox A.; RT "Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and RT methionine at codon 129 of PRNP in previously unreported patients."; RL Neurology 45:1127-1134(1995). RN [49] RP VARIANT GSD LEU-102, AND VARIANT LYS-219. RX MEDLINE=96390486; PubMed=8797472; RA Barbanti P., Fabbrini G., Salvatore M., Petraroli R., Cardone F., RA Maras B., Equestre M., Macchi G., Lenzi G.L., Pocchiari M.; RT "Polymorphism at codon 129 or codon 219 of PRNP and clinical RT heterogeneity in a previously unreported family with Gerstmann- RT Straussler-Scheinker disease (PrP-P102L mutation)."; RL Neurology 47:734-741(1996). RN [50] RP VARIANT CJD HIS-208. RX MEDLINE=97065966; PubMed=8909447; RA Mastrianni J.A., Iannicola C., Myers R.M., Dearmond S., Prusiner S.B.; RT "Mutation of the prion protein gene at codon 208 in familial RT Creutzfeldt-Jakob disease."; RL Neurology 47:1305-1312(1996). RN [51] RP VARIANT CJD HIS-208. RX MEDLINE=97410007; PubMed=9266722; DOI=10.1002/ana.410420203; RA Nitrini R., Rosemberg S., Passos-Bueno M.R., da Silva L.S., RA Iughetti P., Papadopoulos M., Carrilho P.M., Caramelli P., RA Albrecht S., Zatz M., Leblanc A.; RT "Familial spongiform encephalopathy associated with a novel prion RT protein gene mutation."; RL Ann. Neurol. 42:138-146(1997). RN [52] RP VARIANTS GSD ASN-202 AND PRO-212. RX MEDLINE=99000187; PubMed=9786248; RA Piccardo P., Dlouhy S.R., Lievens P.M., Young K., Bird T.D., RA Nochlin D., Dickson D.W., Vinters H.V., Zimmerman T.R., RA Mackenzie I.R., Kish S.J., Ang L.C., De Carli C., Pocchiari M., RA Brown P., Gibbs C.J. Jr., Gajdusek D.C., Bugiani O., Ironside J., RA Tagliavini F., Ghetti B.; RT "Phenotypic variability of Gerstmann-Straussler-Scheinker disease is RT associated with prion protein heterogeneity."; RL J. Neuropathol. Exp. Neurol. 57:979-988(1998). RN [53] RP VARIANTS ARG-188 AND SER-238. RX MEDLINE=20441959; PubMed=10987652; DOI=10.1007/s004390051096; RA Windl O., Giese A., Schulz-Schaeffer W., Zerr I., Skworc K., RA Arendt S., Oberdieck C., Bodemer M., Poser S., Kretzschmar H.A.; RT "Molecular genetics of human prion diseases in Germany."; RL Hum. Genet. 105:244-252(1999). RN [54] RP VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188. RX MEDLINE=20100613; PubMed=10631141; DOI=10.1086/302702; RA Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., RA Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.; RT "High prevalence of pathogenic mutations in patients with early-onset RT dementia detected by sequence analyses of four different genes."; RL Am. J. Hum. Genet. 66:110-117(2000). RN [55] RP VARIANTS CJD LYS-196; ILE-203 AND GLN-211. RX PubMed=10790216; RX DOI=10.1002/(SICI)1098-1004(200005)15:5<482::AID-HUMU16>3.0.CO;2-1; RA Peoc'h K., Manivet P., Beaudry P., Attane F., Besson G., Didier H., RA Delasnerie-Laupretre N., Laplanche J.-L.; RT "Identification of three novel mutations (E196K, V203I, E211Q) in the RT prion protein gene (PRNP) in inherited prion diseases with RT Creutzfeldt-Jakob disease phenotype."; RL Hum. Mutat. 15:482-482(2000). RN [56] RP VARIANT GSD VAL-131. RX MEDLINE=21565836; PubMed=11709001; DOI=10.1001/archneur.58.11.1899; RA Panegyres P.K., Toufexis K., Kakulas B.A., Cernevakova L., Brown P., RA Ghetti B., Piccardo P., Dlouhy S.R.; RT "A new PRNP mutation (G131V) associated with Gerstmann-Straussler- RT Scheinker disease."; RL Arch. Neurol. 58:1899-1902(2001). CC -!- FUNCTION: May play a role in neuronal development and synaptic CC plasticity. May be required for neuronal myelin sheath CC maintenance. May play a role in iron uptake and iron homeostasis. CC Soluble oligomers are toxic to cultured neuroblastoma cells and CC induce apoptosis (in vitro). Association with GPC1 (via its CC heparan sulfate chains) targets PRNP to lipid rafts. Also provides CC Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase CC degradation of its heparan sulfate side chains (By similarity). 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 CC an intermediate stage on the path to fibril formation. Copper CC binding may promote oligomerization. Interacts with GRB2, APP, CC ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP CC interacts with MGRN1; this interaction alters MGRN1 subcellular CC location and causes lysosomal enlargement (By similarity). CC Interacts with KIAA1191. CC -!- INTERACTION: CC Self; NbExp=10; IntAct=EBI-977302, EBI-977302; CC Q9BSJ6:FAM64A; NbExp=5; IntAct=EBI-977302, EBI-2568609; CC P49639:HOXA1; NbExp=4; IntAct=EBI-977302, EBI-740785; CC P29372:MPG; NbExp=4; IntAct=EBI-977302, EBI-1043398; CC Q9H4B4:PLK3; NbExp=4; IntAct=EBI-977302, EBI-751877; CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. CC Golgi apparatus. Note=Targeted to lipid rafts via association with CC the heparan sulfate chains of GPC1. Colocates, in the presence of CC CU(2+), to vesicles in para- and perinuclear regions, where both CC proteins undergo internalization. Heparin displaces PRNP from CC lipid rafts and promotes endocytosis. CC -!- SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus. CC Note=Accumulates outside the secretory route in the cytoplasm, CC from where it relocates to the nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; CC IsoId=P04156-1; Sequence=Displayed; CC Name=2; Synonyms=PrP(M8); CC IsoId=P04156-2; Sequence=VSP_039045; CC -!- DOMAIN: The normal, monomeric form, PRPN(C), has a mainly alpha- CC helical structure. Misfolding of this form produces a disease- CC associated, protease-resistant form, PRPN (Sc), accompanied by a CC large increase of the beta-sheet content and formation of amyloid CC fibrils. These fibrils consist of a cross-beta spine, formed by a CC steric zipper of superposed beta-strands. Disease mutations may CC favor intermolecular contacts via short beta strands, and may CC thereby trigger oligomerization. In addition, the heparan-sulfate CC proteoglycan, GPC1, promotes the association of PRPN (C) to lipid CC rafts and appears to facilitate the conversion to PRPN (Sc). CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. CC At low copper concentrations, the sidechains of His residues from CC three or four repeats contribute to the binding of a single copper CC ion. Alternatively, a copper ion can be bound by interaction with CC the sidechain and backbone amide nitrogen of a single His residue. CC The observed copper binding stoichiometry suggests that two repeat CC regions cooperate to stabilize the binding of a single copper ion. CC At higher copper concentrations, each octamer can bind one copper CC ion by interactions with the His sidechain and Gly backbone atoms. CC A mixture of binding types may occur, especially in the case of CC octamer repeat expansion. Copper binding may stabilize the CC conformation of this region and may promote oligomerization. CC -!- PTM: The glycosylation pattern (the amount of mono-, di- and non- CC glycosylated forms or glycoforms) seems to differ in normal and CC CJD prion. CC -!- PTM: Isoform 2 is sumoylated with SUMO1 (By similarity). CC -!- POLYMORPHISM: The five tandem octapeptide repeats region is highly CC unstable. Insertions or deletions of octapeptide repeat units are CC associated to prion disease. CC -!- DISEASE: Note=PrP is found in high quantity in the brain of humans CC and animals infected with neurodegenerative diseases known as CC transmissible spongiform encephalopathies or prion diseases, like: CC Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), CC Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 CC (HDL1) and kuru in humans; scrapie in sheep and goat; bovine CC spongiform encephalopathy (BSE) in cattle; transmissible mink CC encephalopathy (TME); chronic wasting disease (CWD) of mule deer CC and elk; feline spongiform encephalopathy (FSE) in cats and exotic CC ungulate encephalopathy (EUE) in nyala and greater kudu. The prion CC diseases illustrate three manifestations of CNS degeneration: (1) CC infectious (2) sporadic and (3) dominantly inherited forms. TME, CC CWD, BSE, FSE, EUE are all thought to occur after consumption of CC prion-infected foodstuffs. CC -!- DISEASE: Defects in PRNP are the cause of Creutzfeldt-Jakob CC disease (CJD) [MIM:123400]. CJD occurs primarily as a sporadic CC disorder (1 per million), while 10-15% are familial. Accidental CC transmission of CJD to humans appears to be iatrogenic CC (contaminated human growth hormone (HGH), corneal transplantation, CC electroencephalographic electrode implantation, etc.). CC Epidemiologic studies have failed to implicate the ingestion of CC infected annimal meat in the pathogenesis of CJD in human. The CC triad of microscopic features that characterize the prion diseases CC consists of (1) spongiform degeneration of neurons, (2) severe CC astrocytic gliosis that often appears to be out of proportion to CC the degree of nerve cell loss, and (3) amyloid plaque formation. CC CJD is characterized by progressive dementia and myoclonic CC seizures, affecting adults in mid-life. Some patients present CC sleep disorders, abnormalities of high cortical function, CC cerebellar and corticospinal disturbances. The disease ends in CC death after a 3-12 months illness. CC -!- DISEASE: Defects in PRNP are the cause of fatal familial insomnia CC (FFI) [MIM:600072]. FFI is an autosomal dominant disorder and is CC characterized by neuronal degeneration limited to selected CC thalamic nuclei and progressive insomnia. CC -!- DISEASE: Defects in PRNP are the cause of Gerstmann-Straussler CC disease (GSD) [MIM:137440]. GSD is a heterogeneous disorder and CC was defined as a spinocerebellar ataxia with dementia and CC plaquelike deposits. GSD incidence is less than 2 per 100 million CC live births. CC -!- DISEASE: Defects in PRNP are the cause of Huntington disease-like CC type 1 (HDL1) [MIM:603218]. HDL1 is an autosomal dominant, early CC onset neurodegenerative disorder with prominent psychiatric CC features. CC -!- DISEASE: Defects in PRNP are the cause of kuru (KURU) CC [MIM:245300]. Kuru is transmitted during ritualistic cannibalism, CC among natives of the New Guinea highlands. Patients exhibit CC various movement disorders like cerebellar abnormalities, rigidity CC of the limbs, and clonus. Emotional lability is present, and CC dementia is conspicuously absent. Death usually occurs from 3 to CC 12 month after onset. CC -!- DISEASE: Defects in PRNP are the cause of spongiform CC encephalopathy with neuropsychiatric features (SENF) [MIM:606688]; CC an autosomal dominant presenile dementia with a rapidly CC progressive and protracted clinical course. The dementia was CC characterized clinically by frontotemporal features, including CC early personality changes. Some patients had memory loss, several CC showed aggressiveness, hyperorality and verbal stereotypy, others CC had parkinsonian symptoms. CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene CC which also produces the The alternative prion protein/AltPrP from CC an overlapping reading frame. CC -!- MISCELLANEOUS: The alternative prion protein/AltPrP (AC F7VJQ1) CC and PRNP have no apparent direct functional relation since a CC mutation that removes the start codon of the AltPrP has no CC apparent effect on the biology of PRNP. In mouse and hamster, the CC alternative initiation AUG codon is absent and is replaced by a CC GUG codon. CC -!- SIMILARITY: Belongs to the prion family. CC -!- WEB RESOURCE: Name=The Official Mad Cow Disease Home Page; CC URL="http://www.mad-cow.org/"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PRNP"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=PRNP entry; CC URL="http://en.wikipedia.org/wiki/PRNP"; 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; M13899; AAA60182.1; -; mRNA. DR EMBL; X83416; CAA58442.1; -; Genomic_DNA. DR EMBL; U29185; AAC78725.1; -; Genomic_DNA. DR EMBL; AF076976; AAD46098.1; -; Genomic_DNA. DR EMBL; AY008282; AAG21693.1; -; mRNA. DR EMBL; DQ408531; ABD63004.1; -; Genomic_DNA. DR EMBL; AL133396; CAB75503.1; -; Genomic_DNA. DR EMBL; AL133396; CAI19053.1; -; Genomic_DNA. DR EMBL; BC012844; AAH12844.1; -; mRNA. DR EMBL; BC022532; AAH22532.1; -; mRNA. DR EMBL; D00015; BAA00011.1; -; mRNA. DR EMBL; M13667; AAA19664.1; -; mRNA. DR EMBL; M81929; AAB59442.1; -; Genomic_DNA. DR EMBL; M81930; AAB59443.1; -; Genomic_DNA. DR EMBL; AF030575; AAC05365.1; -; Genomic_DNA. DR EMBL; S80732; AAB50648.2; -; Genomic_DNA. DR EMBL; S80743; AAB50649.2; -; Genomic_DNA. DR EMBL; S71208; AAB20521.1; -; Genomic_DNA. DR EMBL; S71210; AAB20522.1; -; Genomic_DNA. DR EMBL; S71212; AAB20523.1; -; Genomic_DNA. DR IPI; IPI00022284; -. DR IPI; IPI00956325; -. DR PIR; A24173; UJHU. DR RefSeq; NP_000302.1; NM_000311.3. DR RefSeq; NP_001073590.1; NM_001080121.1. DR RefSeq; NP_001073591.1; NM_001080122.1. DR RefSeq; NP_001073592.1; NM_001080123.1. DR RefSeq; NP_898902.1; NM_183079.2. DR UniGene; Hs.472010; -. DR UniGene; Hs.597483; -. DR UniGene; Hs.610285; -. DR UniGene; Hs.721670; -. DR PDB; 1E1G; NMR; -; A=125-228. DR PDB; 1E1J; NMR; -; A=125-228. DR PDB; 1E1P; NMR; -; A=125-228. DR PDB; 1E1S; NMR; -; A=125-228. DR PDB; 1E1U; NMR; -; A=125-228. DR PDB; 1E1W; NMR; -; A=125-228. DR PDB; 1FKC; NMR; -; A=90-231. DR PDB; 1FO7; NMR; -; A=90-231. DR PDB; 1H0L; NMR; -; A=121-230. DR PDB; 1HJM; NMR; -; A=125-228. DR PDB; 1HJN; NMR; -; A=125-228. DR PDB; 1I4M; X-ray; 2.00 A; A=119-226. DR PDB; 1OEH; NMR; -; A=61-68. DR PDB; 1OEI; NMR; -; A=61-84. DR PDB; 1QLX; NMR; -; A=23-230. DR PDB; 1QLZ; NMR; -; A=23-230. DR PDB; 1QM0; NMR; -; A=90-230. DR PDB; 1QM1; NMR; -; A=90-230. DR PDB; 1QM2; NMR; -; A=121-230. DR PDB; 1QM3; NMR; -; A=121-230. DR PDB; 2IV4; NMR; -; A=180-195. DR PDB; 2IV5; NMR; -; A=173-195. DR PDB; 2IV6; NMR; -; A=173-195. DR PDB; 2K1D; NMR; -; A=90-231. DR PDB; 2KUN; NMR; -; A=90-231. DR PDB; 2LBG; NMR; -; A=110-136. DR PDB; 2LEJ; NMR; -; A=90-231. DR PDB; 2LFT; NMR; -; A=90-231. DR PDB; 2LSB; NMR; -; A=90-231. DR PDB; 2LV1; NMR; -; A=90-231. DR PDB; 2OL9; X-ray; 0.85 A; A=170-175. DR PDB; 2W9E; X-ray; 2.90 A; A=119-231. DR PDB; 3HAF; X-ray; 2.26 A; A=90-231. DR PDB; 3HAK; X-ray; 1.80 A; A=125-227. DR PDB; 3HEQ; X-ray; 1.80 A; A/B=90-231. DR PDB; 3HER; X-ray; 1.85 A; A/B=90-231. DR PDB; 3HES; X-ray; 2.00 A; A/B=90-231. DR PDB; 3HJ5; X-ray; 3.10 A; A/B=90-231. DR PDB; 3HJX; X-ray; 2.00 A; A=126-231. DR PDB; 3MD4; X-ray; 1.15 A; A/B=127-132. DR PDB; 3MD5; X-ray; 1.40 A; A/B=127-132. DR PDB; 3NHC; X-ray; 1.57 A; A/B=127-132. DR PDB; 3NHD; X-ray; 1.92 A; A/B=127-132. DR PDB; 3NVF; X-ray; 1.80 A; A=138-143. DR PDBsum; 1E1G; -. DR PDBsum; 1E1J; -. DR PDBsum; 1E1P; -. DR PDBsum; 1E1S; -. DR PDBsum; 1E1U; -. DR PDBsum; 1E1W; -. DR PDBsum; 1FKC; -. DR PDBsum; 1FO7; -. DR PDBsum; 1H0L; -. DR PDBsum; 1HJM; -. DR PDBsum; 1HJN; -. DR PDBsum; 1I4M; -. DR PDBsum; 1OEH; -. DR PDBsum; 1OEI; -. DR PDBsum; 1QLX; -. DR PDBsum; 1QLZ; -. DR PDBsum; 1QM0; -. DR PDBsum; 1QM1; -. DR PDBsum; 1QM2; -. DR PDBsum; 1QM3; -. DR PDBsum; 2IV4; -. DR PDBsum; 2IV5; -. DR PDBsum; 2IV6; -. DR PDBsum; 2K1D; -. DR PDBsum; 2KUN; -. DR PDBsum; 2LBG; -. DR PDBsum; 2LEJ; -. DR PDBsum; 2LFT; -. DR PDBsum; 2LSB; -. DR PDBsum; 2LV1; -. DR PDBsum; 2OL9; -. DR PDBsum; 2W9E; -. DR PDBsum; 3HAF; -. DR PDBsum; 3HAK; -. DR PDBsum; 3HEQ; -. DR PDBsum; 3HER; -. DR PDBsum; 3HES; -. DR PDBsum; 3HJ5; -. DR PDBsum; 3HJX; -. DR PDBsum; 3MD4; -. DR PDBsum; 3MD5; -. DR PDBsum; 3NHC; -. DR PDBsum; 3NHD; -. DR PDBsum; 3NVF; -. DR DisProt; DP00466; -. DR ProteinModelPortal; P04156; -. DR SMR; P04156; 2-28, 57-231. DR DIP; DIP-29933N; -. DR IntAct; P04156; 57. DR MINT; MINT-1420984; -. DR STRING; P04156; -. DR PhosphoSite; P04156; -. DR DMDM; 130912; -. DR PaxDb; P04156; -. DR PRIDE; P04156; -. DR DNASU; 5621; -. DR Ensembl; ENST00000379440; ENSP00000368752; ENSG00000171867. DR Ensembl; ENST00000430350; ENSP00000399376; ENSG00000171867. DR Ensembl; ENST00000457586; ENSP00000415284; ENSG00000171867. DR GeneID; 5621; -. DR KEGG; hsa:5621; -. DR UCSC; uc002wkt.1; human. DR CTD; 5621; -. DR GeneCards; GC20P004615; -. DR HGNC; HGNC:9449; PRNP. DR HPA; HPA042754; -. DR MIM; 123400; phenotype. DR MIM; 137440; phenotype. DR MIM; 176640; gene. DR MIM; 245300; phenotype. DR MIM; 600072; phenotype. DR MIM; 603218; phenotype. DR MIM; 606688; phenotype. DR neXtProt; NX_P04156; -. DR Orphanet; 204; Creutzfeldt-Jakob disease. DR Orphanet; 280397; Familial prion disease Alzheimer-like. DR Orphanet; 466; Fatal familial insomnia. DR Orphanet; 356; Gerstmann-Straussler-Scheinker syndrome. DR Orphanet; 157941; Huntington disease-like 1. DR PharmGKB; PA33796; -. DR eggNOG; NOG41716; -. DR HOVERGEN; HBG008260; -. DR InParanoid; P04156; -. DR KO; K05634; -. DR OMA; GYPHNPG; -. DR OrthoDB; EOG4HDSW2; -. DR PhylomeDB; P04156; -. DR Pathway_Interaction_DB; glypican_1pathway; Glypican 1 network. DR Reactome; REACT_111045; Developmental Biology. DR ChEMBL; CHEMBL4869; -. DR DrugBank; DB00759; Tetracycline. DR EvolutionaryTrace; P04156; -. DR GenomeRNAi; 5621; -. DR NextBio; 21844; -. DR PMAP-CutDB; P04156; -. DR ArrayExpress; P04156; -. DR Bgee; P04156; -. DR Genevestigator; P04156; -. DR GermOnline; ENSG00000171867; Homo sapiens. DR GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0019898; C:extrinsic to membrane; TAS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0006916; P:anti-apoptosis; IEA:Compara. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007050; P:cell cycle arrest; IEA:UniProtKB-KW. DR GO; GO:0006878; P:cellular copper ion homeostasis; NAS:UniProtKB. DR GO; GO:0008152; P:metabolic process; TAS:ProtInc. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:BHF-UCL. DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:BHF-UCL. DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISS:BHF-UCL. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISS:BHF-UCL. DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISS:BHF-UCL. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:BHF-UCL. DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; ISS:BHF-UCL. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR GO; GO:0046686; P:response to cadmium ion; IEA:Compara. DR GO; GO:0046688; P:response to copper ion; IEA:Compara. DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB. DR Gene3D; 1.10.790.10; Prion; 1. DR InterPro; IPR000817; Prion. DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom. DR InterPro; IPR025860; Prion_N_dom. DR PANTHER; PTHR11522; PTHR11522; 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; 1. DR PROSITE; PS00291; PRION_1; 1. DR PROSITE; PS00706; PRION_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Amyloid; Cell cycle; KW Cell membrane; Complete proteome; Copper; Cytoplasm; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Golgi apparatus; GPI-anchor; Growth arrest; Lipoprotein; KW Membrane; Metal-binding; Nucleus; Polymorphism; Prion; KW Reference proteome; Repeat; Signal; Ubl conjugation; Zinc. FT SIGNAL 1 22 FT CHAIN 23 230 Major prion protein. FT /FTId=PRO_0000025675. FT PROPEP 231 253 Removed in mature form (By similarity). FT /FTId=PRO_0000025676. FT REPEAT 51 59 1. FT REPEAT 60 67 2. FT REPEAT 68 75 3. FT REPEAT 76 83 4. FT REPEAT 84 91 5. FT REGION 23 230 Interaction with GRB2, ERI3 and SYN1 (By FT similarity). FT REGION 51 91 5 X 8 AA tandem repeats of P-H-G-G-G-W-G- FT Q. FT METAL 61 61 Copper or zinc 1. FT METAL 62 62 Copper or zinc 1; via amide nitrogen. FT METAL 63 63 Copper or zinc 1; via amide nitrogen and FT carbonyl oxygen. FT METAL 69 69 Copper or zinc 2 (Probable). FT METAL 70 70 Copper or zinc 2; via amide nitrogen FT (Probable). FT METAL 71 71 Copper or zinc 2; via amide nitrogen and FT carbonyl oxygen (Probable). FT METAL 77 77 Copper or zinc 3 (Probable). FT METAL 78 78 Copper or zinc 3; via amide nitrogen FT (Probable). FT METAL 79 79 Copper or zinc 3; via amide nitrogen and FT carbonyl oxygen (Probable). FT METAL 85 85 Copper or zinc 4 (Probable). FT METAL 86 86 Copper or zinc 4; via amide nitrogen FT (Probable). FT METAL 87 87 Copper or zinc 4; via amide nitrogen and FT carbonyl oxygen (Probable). FT LIPID 230 230 GPI-anchor amidated serine (By FT similarity). FT CARBOHYD 181 181 N-linked (GlcNAc...). FT CARBOHYD 197 197 N-linked (GlcNAc...). FT DISULFID 179 214 FT VAR_SEQ 1 7 Missing (in isoform 2). FT /FTId=VSP_039045. FT VARIANT 56 63 Missing. FT /FTId=VAR_013763. FT VARIANT 102 102 P -> L (in GSD and early-onset dementia). FT /FTId=VAR_006464. FT VARIANT 105 105 P -> L (in GSD). FT /FTId=VAR_006465. FT VARIANT 117 117 A -> V (linked to development of FT dementing Gerstmann-Straussler disease). FT /FTId=VAR_006466. FT VARIANT 129 129 M -> V (polymorphism; determines the FT disease phenotype in patients who have a FT PrP mutation at position 178. Patients FT with M-129 develop FFI, those with V-129 FT develop CJD; dbSNP:rs1799990). FT /FTId=VAR_006467. FT VARIANT 131 131 G -> V (in GSD). FT /FTId=VAR_014264. FT VARIANT 171 171 N -> S (in schizoaffective disorder; FT dbSNP:rs16990018). FT /FTId=VAR_006468. FT VARIANT 178 178 D -> N (in FFI and CJD). FT /FTId=VAR_006469. FT VARIANT 180 180 V -> I (in CJD). FT /FTId=VAR_006470. FT VARIANT 183 183 T -> A (in familial spongiform FT encephalopathy). FT /FTId=VAR_006471. FT VARIANT 187 187 H -> R (in GSD). FT /FTId=VAR_008746. FT VARIANT 188 188 T -> K (in early-onset dementia; dementia FT associated to prion diseases). FT /FTId=VAR_008748. FT VARIANT 188 188 T -> R. FT /FTId=VAR_008747. FT VARIANT 196 196 E -> K (in CJD). FT /FTId=VAR_008749. FT VARIANT 198 198 F -> S (in GSD; atypical form with FT neurofibrillary tangles). FT /FTId=VAR_006472. FT VARIANT 200 200 E -> K (in CJD). FT /FTId=VAR_006473. FT VARIANT 202 202 D -> N (in GSD). FT /FTId=VAR_008750. FT VARIANT 203 203 V -> I (in CJD; it could be an extremely FT rare polymorphism). FT /FTId=VAR_008751. FT VARIANT 208 208 R -> H (in CJD). FT /FTId=VAR_006474. FT VARIANT 210 210 V -> I (in CJD). FT /FTId=VAR_006475. FT VARIANT 211 211 E -> Q (in CJD). FT /FTId=VAR_008752. FT VARIANT 212 212 Q -> P (in GSD). FT /FTId=VAR_008753. FT VARIANT 217 217 Q -> R (in GSD; with neurofibrillary FT tangles). FT /FTId=VAR_006476. FT VARIANT 219 219 E -> K (in dbSNP:rs1800014). FT /FTId=VAR_006477. FT VARIANT 232 232 M -> R (in CJD). FT /FTId=VAR_006478. FT VARIANT 238 238 P -> S. FT /FTId=VAR_008754. FT MUTAGEN 1 1 M->S: Protein detected. No protein FT detected; when associated with S-8. FT MUTAGEN 8 8 M->S: No protein detected; when FT associated with S-1. FT CONFLICT 118 118 Missing (in Ref. 9; AAA19664/BAA00011). FT CONFLICT 169 169 Y -> H (in Ref. 6; ABD63004). FT CONFLICT 227 227 Q -> K (in Ref. 8; AAH22532). FT STRAND 63 66 FT STRAND 70 73 FT TURN 74 76 FT STRAND 78 82 FT STRAND 125 127 FT STRAND 128 131 FT STRAND 141 143 FT HELIX 144 153 FT HELIX 154 156 FT STRAND 159 163 FT HELIX 165 169 FT HELIX 172 192 FT TURN 193 195 FT HELIX 200 226 FT TURN 228 230 SQ SEQUENCE 253 AA; 27661 MW; 43DB596BAAA66484 CRC64; MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGGGWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HMAGAAAAGA VVGGLGGYML GSAMSRPIIH FGSDYEDRYY RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV ILLISFLIFL IVG //