PRIO_HUMAN
ID PRIO_HUMAN Reviewed; 253 AA.
AC P04156; O60489; P78446; Q15216; Q15221; Q27H91; Q5QPB4; Q8TBG0; Q96E70;
AC Q9UP19;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 263.
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=ALTPRP, PRIP, PRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3755672; DOI=10.1089/dna.1986.5.315;
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 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 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 [GENOMIC DNA], AND VARIANT GSD ARG-187.
RC TISSUE=Blood;
RX 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 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., Romas N.A.,
RA 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., Liu X.;
RT "Analysis and comparison of several mammalian prion protein genes Prnp.";
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-253.
RX 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 DEL.
RC TISSUE=Brain;
RX PubMed=1363802; DOI=10.1093/hmg/1.6.443;
RA Diedrich J.F., Knopman D.S., List J.F., Olson K., Frey W.H., Emory C.R.,
RA 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 SCHIZOAFFECTIVE
RP DISORDER SER-171.
RX 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 DEL.
RX 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 disease
RT family.";
RL Am. J. Med. Genet. 60:12-18(1995).
RN [13]
RP PROTEIN SEQUENCE OF 58-85 AND 111-150.
RX PubMed=1672107; DOI=10.1002/j.1460-2075.1991.tb07977.x;
RA Tagliavini F., Prelli F., Ghiso J., Bugiani O., Serban D., Prusiner S.B.,
RA 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 glycine
RT at codon 58.";
RL EMBO J. 10:513-519(1991).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-91.
RX 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 five,
RT seven, and eight extra octapeptide coding repeats in the PRNP gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10926-10930(1991).
RN [15]
RP INVOLVEMENT IN HDL1.
RX PubMed=9792871; DOI=10.1086/302093;
RA Xiang F., Almqvist E.W., Huq M., Lundin A., Hayden M.R., Edstroem L.,
RA Anvret M., Zhang Z.;
RT "A Huntington disease-like neurodegenerative disorder maps to chromosome
RT 20p.";
RL Am. J. Hum. Genet. 63:1431-1438(1998).
RN [16]
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 S-
RT nitroso-dependent autocleavage of glypican-1 heparan sulfate.";
RL J. Biol. Chem. 278:38956-38965(2003).
RN [17]
RP GLYCOSYLATION AT ASN-181, VARIANT SENF ALA-183, AND CHARACTERIZATION OF
RP VARIANT SENF ALA-183.
RX PubMed=12214108; DOI=10.3233/jad-2000-2104;
RA Capellari S., Zaidi S.I., Long A.C., Kwon E.E., Petersen R.B.;
RT "The Thr183Ala mutation, not the loss of the first glycosylation site,
RT alters the physical properties of the prion protein.";
RL J. Alzheimers Dis. 2:27-35(2000).
RN [18]
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., Antholine W.E.,
RA 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 [19]
RP COPPER-BINDING, 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 [20]
RP RETRACTED PAPER.
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 alternative
RT initiation of translation.";
RL J. Biol. Chem. 284:2787-2794(2009).
RN [21]
RP RETRACTION NOTICE OF PUBMED:19059915.
RX PubMed=29222195; DOI=10.1074/jbc.w117.000658;
RA Juanes M.E., Elvira G., Garcia-Grande A., Calero M., Gasset M.;
RT "Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative
RT initiation of translation.";
RL J. Biol. Chem. 292:20044-20044(2017).
RN [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197.
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-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [23]
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 disease
RT isoform formation.";
RL PLoS Pathog. 5:E1000666-E1000666(2009).
RN [24]
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 [25]
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 [26]
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 oligomers in
RT acidic environment.";
RL J. Cell. Biochem. 111:627-633(2010).
RN [27]
RP BICISTRONIC GENE.
RX PubMed=21478263; DOI=10.1096/fj.10-173815;
RA Vanderperre B., Staskevicius A.B., Tremblay G., McCoy M., O'Neill M.A.,
RA Cashman N.R., Roucou X.;
RT "An overlapping reading frame in the PRNP gene encodes a novel polypeptide
RT distinct from the prion protein.";
RL FASEB J. 25:2373-2386(2011).
RN [28]
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 [29]
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., 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 [30]
RP STRUCTURE BY NMR OF 23-230.
RX PubMed=10618385; DOI=10.1073/pnas.97.1.145;
RA Zahn R., Liu A., Luhrs T., Riek R., von Schroetter C., Lopez Garcia F.,
RA 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 [31]
RP STRUCTURE BY NMR OF 118-221.
RX PubMed=10900000; DOI=10.1073/pnas.97.15.8340;
RA Calzolai L., Lysek D.A., Guntert P., von Schroetter C., Riek R., Zahn R.,
RA 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 [32]
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., 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 [33]
RP X-RAY CRYSTALLOGRAPHY (0.75 ANGSTROMS) OF 61-65 IN COMPLEX WITH COPPER ION,
RP 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 domain of
RT the prion protein.";
RL Biochemistry 41:3991-4001(2002).
RN [34]
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 [35]
RP REVIEW ON VARIANTS.
RX 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 [36]
RP REVIEW ON VARIANTS, AND INVOLVEMENT IN PRION DISEASES.
RX PubMed=8105771; DOI=10.1001/archneur.1993.00540110011002;
RA Prusiner S.B.;
RT "Genetic and infectious prion diseases.";
RL Arch. Neurol. 50:1129-1153(1993).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 170-175, SUBUNIT, AND 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., McFarlane H.T.,
RA 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 [38]
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 [39]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 125-227 OF VARIANT VAL-129,
RP VARIANT VAL-129, VARIANT CJD ASN-178, VARIANT FFI ASN-178, VARIANT GSD
RP 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., Surewicz W.K.,
RA Yee V.C.;
RT "Conformational diversity in prion protein variants influences
RT intermolecular beta-sheet formation.";
RL EMBO J. 29:251-262(2010).
RN [40]
RP VARIANT GSD LEU-102.
RX PubMed=2564168; DOI=10.1038/338342a0;
RA Hsiao K., Baker H.F., Crow T.J., Poulter M., Owen F., Terwilliger J.D.,
RA 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 [41]
RP VARIANTS LEU-102; VAL-117 AND VAL-129.
RX 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 but
RT not the sole mutation related to Gerstmann-Straussler syndrome.";
RL Biochem. Biophys. Res. Commun. 163:974-979(1989).
RN [42]
RP VARIANT FFI ASN-178.
RX PubMed=1347910; DOI=10.1212/wnl.42.3.669;
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 protein
RT gene at codon 178.";
RL Neurology 42:669-670(1992).
RN [43]
RP VARIANT CJD ASN-178.
RX PubMed=1671440; DOI=10.1016/0140-6736(91)91198-4;
RA Goldfarb L.G., Haltia M., Brown P., Nieto A., Kovanen J., McCombie W.R.,
RA Trapp S., Gajdusek D.C.;
RT "New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish
RT Creutzfeldt-Jakob kindred.";
RL Lancet 337:425-425(1991).
RN [44]
RP VARIANT CJD LYS-200.
RX 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 of
RT Creutzfeldt-Jakob disease in Slovakia.";
RL Lancet 336:514-515(1990).
RN [45]
RP VARIANT GSD ARG-217.
RX PubMed=1363810; DOI=10.1038/ng0492-68;
RA Hsiao K., Dlouhy S.R., Farlow M.R., Cass C., da Costa M., Conneally P.M.,
RA 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 [46]
RP VARIANT VAL-129, VARIANT CJD ASN-178, VARIANT FFI ASN-178, CHARACTERIZATION
RP OF VARIANT VAL-129, CHARACTERIZATION OF VARIANT CJD ASN-178,
RP CHARACTERIZATION OF VARIANT FFI ASN-178, AND POLYMORPHISM.
RX PubMed=1439789; DOI=10.1126/science.1439789;
RA Goldfarb L.G., Petersen R.B., Tabaton M., Brown P., LeBlanc A.C.,
RA Montagna P., Cortelli P., Julien J., Vital C., Pendelbury W.W.;
RT "Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease
RT phenotype determined by a DNA polymorphism.";
RL Science 258:806-808(1992).
RN [47]
RP VARIANTS CJD ILE-180 AND ARG-232.
RX 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 or
RT Gerstmann-Straussler syndrome.";
RL Biochem. Biophys. Res. Commun. 191:709-714(1993).
RN [48]
RP VARIANT CJD ILE-210.
RX PubMed=7902693; DOI=10.1002/ana.410340608;
RA Pocchiari M., Salvatore M., Cutruzzola F., Genuardi M., Allcatelli C.T.,
RA Masullo C., Macchi G., Alema G., Galgani S., Xi Y.G., Petraroli R.,
RA 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 [49]
RP VARIANT GSD LEU-105.
RX PubMed=7902972; DOI=10.1212/wnl.43.12.2723-a;
RA Yamada M., Itoh Y., Fujigasaki H., Naruse S., Kaneko K., Kitamoto T.,
RA Tateishi J., Otomo E., Hayakawa M., Tanaka J., Matsushita M., Miyatake T.;
RT "A missense mutation at codon 105 with codon 129 polymorphism of the prion
RT protein gene in a new variant of Gerstmann-Straussler-Scheinker disease.";
RL Neurology 43:2723-2724(1993).
RN [50]
RP VARIANT GSD LEU-105.
RX 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 105
RT mutation with codon 129 polymorphism of the prion protein gene: a
RT clinicopathological study.";
RL J. Neurol. Sci. 127:77-86(1994).
RN [51]
RP VARIANT CJD LYS-200.
RX PubMed=7906019; DOI=10.1212/wnl.44.2.299;
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 [52]
RP VARIANT CJD LYS-200.
RX PubMed=7913755; DOI=10.1098/rstb.1994.0033;
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 protein
RT gene in Libyan Jews with Creutzfeldt-Jakob disease.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 343:385-390(1994).
RN [53]
RP VARIANT GSD LEU-102.
RX PubMed=7783876; DOI=10.1212/wnl.45.6.1127;
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 [54]
RP VARIANT GSD LEU-102, AND VARIANT LYS-219.
RX PubMed=8797472; DOI=10.1212/wnl.47.3.734;
RA Barbanti P., Fabbrini G., Salvatore M., Petraroli R., Cardone F., Maras B.,
RA Equestre M., Macchi G., Lenzi G.L., Pocchiari M.;
RT "Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity
RT in a previously unreported family with Gerstmann-Straussler-Scheinker
RT disease (PrP-P102L mutation).";
RL Neurology 47:734-741(1996).
RN [55]
RP VARIANT CJD HIS-208.
RX PubMed=8909447; DOI=10.1212/wnl.47.5.1305;
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 Creutzfeldt-
RT Jakob disease.";
RL Neurology 47:1305-1312(1996).
RN [56]
RP VARIANT SENF ALA-183.
RX PubMed=9266722; DOI=10.1002/ana.410420203;
RA Nitrini R., Rosemberg S., Passos-Bueno M.R., da Silva L.S., Iughetti P.,
RA Papadopoulos M., Carrilho P.M., Caramelli P., Albrecht S., Zatz M.,
RA Leblanc A.;
RT "Familial spongiform encephalopathy associated with a novel prion protein
RT gene mutation.";
RL Ann. Neurol. 42:138-146(1997).
RN [57]
RP VARIANTS GSD ASN-202 AND PRO-212.
RX PubMed=9786248; DOI=10.1097/00005072-199810000-00010;
RA Piccardo P., Dlouhy S.R., Lievens P.M., Young K., Bird T.D., Nochlin D.,
RA Dickson D.W., Vinters H.V., Zimmerman T.R., Mackenzie I.R., Kish S.J.,
RA Ang L.C., De Carli C., Pocchiari M., Brown P., Gibbs C.J. Jr.,
RA Gajdusek D.C., Bugiani O., Ironside J., 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 [58]
RP VARIANT LYS-219, CHARACTERIZATION OF VARIANT LYS-219, AND POLYMORPHISM.
RX PubMed=9482303; DOI=10.1016/s0140-6736(05)78358-6;
RA Shibuya S., Higuchi J., Shin R.W., Tateishi J., Kitamoto T.;
RT "Protective prion protein polymorphisms against sporadic Creutzfeldt-Jakob
RT disease.";
RL Lancet 351:419-419(1998).
RN [59]
RP VARIANTS ARG-188 AND SER-238.
RX PubMed=10987652; DOI=10.1007/s004399900124;
RA Windl O., Giese A., Schulz-Schaeffer W., Zerr I., Skworc K., Arendt S.,
RA 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 [60]
RP VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188.
RX 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 [61]
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 prion
RT protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob
RT disease phenotype.";
RL Hum. Mutat. 15:482-482(2000).
RN [62]
RP VARIANT GSD VAL-131.
RX 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-Scheinker
RT disease.";
RL Arch. Neurol. 58:1899-1902(2001).
RN [63]
RP VARIANT VAL-129, AND CHARACTERIZATION OF VARIANT VAL-129.
RX PubMed=12690204; DOI=10.1126/science.1083320;
RA Mead S., Stumpf M.P., Whitfield J., Beck J.A., Poulter M., Campbell T.,
RA Uphill J.B., Goldstein D., Alpers M., Fisher E.M., Collinge J.;
RT "Balancing selection at the prion protein gene consistent with prehistoric
RT kurulike epidemics.";
RL Science 300:640-643(2003).
RN [64]
RP VARIANT VAL-127, AND INVOLVEMENT IN KURU.
RX PubMed=19923577; DOI=10.1056/nejmoa0809716;
RA Mead S., Whitfield J., Poulter M., Shah P., Uphill J., Campbell T.,
RA Al-Dujaily H., Hummerich H., Beck J., Mein C.A., Verzilli C., Whittaker J.,
RA Alpers M.P., Collinge J.;
RT "A novel protective prion protein variant that colocalizes with kuru
RT exposure.";
RL N. Engl. J. Med. 361:2056-2065(2009).
RN [65]
RP VARIANT VAL-127, CHARACTERIZATION OF VARIANT VAL-127, INVOLVEMENT IN KURU,
RP AND POLYMORPHISM.
RX PubMed=26061765; DOI=10.1038/nature14510;
RA Asante E.A., Smidak M., Grimshaw A., Houghton R., Tomlinson A., Jeelani A.,
RA Jakubcova T., Hamdan S., Richard-Londt A., Linehan J.M., Brandner S.,
RA Alpers M., Whitfield J., Mead S., Wadsworth J.D., Collinge J.;
RT "A naturally occurring variant of the human prion protein completely
RT prevents prion disease.";
RL Nature 522:478-481(2015).
CC -!- FUNCTION: Its primary physiological function is unclear. May play a
CC role in neuronal development and synaptic plasticity. May be required
CC for neuronal myelin sheath maintenance. May promote myelin homeostasis
CC through acting as an agonist for ADGRG6 receptor. May play a role in
CC iron uptake and iron homeostasis. Soluble oligomers are toxic to
CC cultured neuroblastoma cells and induce apoptosis (in vitro) (By
CC similarity). Association with GPC1 (via its heparan sulfate chains)
CC targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the
CC ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate
CC side chains (By similarity). {ECO:0000250|UniProtKB:P04925,
CC ECO:0000269|PubMed:12732622, ECO:0000269|PubMed:19936054,
CC ECO:0000269|PubMed:20564047, ECO:0000305}.
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 (PubMed:11524679, PubMed:11900542,
CC PubMed:14623188, PubMed:17468747, PubMed:19204296, PubMed:19927125,
CC PubMed:20375014, PubMed:20564047). Interacts with GRB2, APP,
CC ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts
CC with MGRN1; this interaction alters MGRN1 subcellular location and
CC causes lysosomal enlargement (By similarity). Interacts with KIAA1191
CC (PubMed:21153684). Interacts with ADGRG6 (By similarity).
CC {ECO:0000250|UniProtKB:P04925, ECO:0000269|PubMed:11524679,
CC ECO:0000269|PubMed:11900542, ECO:0000269|PubMed:14623188,
CC ECO:0000269|PubMed:17468747, ECO:0000269|PubMed:19204296,
CC ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:20375014,
CC ECO:0000269|PubMed:20564047, ECO:0000269|PubMed:21153684}.
CC -!- INTERACTION:
CC P04156; Q9UL18: AGO1; NbExp=2; IntAct=EBI-977302, EBI-527363;
CC P04156; Q9UKV8: AGO2; NbExp=4; IntAct=EBI-977302, EBI-528269;
CC P04156; P05067: APP; NbExp=6; IntAct=EBI-977302, EBI-77613;
CC P04156; P05067-4: APP; NbExp=2; IntAct=EBI-977302, EBI-302641;
CC P04156; PRO_0000000092 [P05067]: APP; NbExp=3; IntAct=EBI-977302, EBI-821758;
CC P04156; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-977302, EBI-2410266;
CC P04156; P25311: AZGP1; NbExp=4; IntAct=EBI-977302, EBI-2513837;
CC P04156; P55085: F2RL1; NbExp=3; IntAct=EBI-977302, EBI-4303189;
CC P04156; Q13642: FHL1; NbExp=3; IntAct=EBI-977302, EBI-912547;
CC P04156; O75084: FZD7; NbExp=3; IntAct=EBI-977302, EBI-746917;
CC P04156; P49639: HOXA1; NbExp=4; IntAct=EBI-977302, EBI-740785;
CC P04156; P42858: HTT; NbExp=13; IntAct=EBI-977302, EBI-466029;
CC P04156; P10636: MAPT; NbExp=2; IntAct=EBI-977302, EBI-366182;
CC P04156; P29372: MPG; NbExp=4; IntAct=EBI-977302, EBI-1043398;
CC P04156; Q9BSJ6: PIMREG; NbExp=5; IntAct=EBI-977302, EBI-2568609;
CC P04156; Q9H4B4: PLK3; NbExp=4; IntAct=EBI-977302, EBI-751877;
CC P04156; Q06830: PRDX1; NbExp=4; IntAct=EBI-977302, EBI-353193;
CC P04156; P04156: PRNP; NbExp=33; IntAct=EBI-977302, EBI-977302;
CC P04156; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-977302, EBI-11528848;
CC P04156; Q8CJG0: Ago2; Xeno; NbExp=2; IntAct=EBI-977302, EBI-528299;
CC P04156; P04925: Prnp; Xeno; NbExp=3; IntAct=EBI-977302, EBI-768613;
CC P04156; P10279: PRNP; Xeno; NbExp=5; IntAct=EBI-977302, EBI-7430632;
CC P04156; P23907: PRNP; Xeno; NbExp=3; IntAct=EBI-977302, EBI-7670302;
CC PRO_0000025675; P31424-2: Grm5; Xeno; NbExp=4; IntAct=EBI-8830282, EBI-8830305;
CC PRO_0000025675; P52480: Pkm; Xeno; NbExp=5; IntAct=EBI-8830282, EBI-647785;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:19936054}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P04925}. 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, where
CC both proteins undergo internalization. Heparin displaces PRNP from
CC lipid rafts and promotes endocytosis. {ECO:0000269|PubMed:19936054}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=PrP;
CC IsoId=P04156-1; Sequence=Displayed;
CC Name=3; Synonyms=AltPrP;
CC IsoId=F7VJQ1-1; Sequence=External;
CC -!- DOMAIN: The normal, monomeric form, PRPN(C), has a mainly alpha-helical
CC structure. Misfolding of this form produces a disease-associated,
CC protease-resistant form, PRPN (Sc), accompanied by a large increase of
CC the beta-sheet content and formation of amyloid fibrils. These fibrils
CC consist of a cross-beta spine, formed by a steric zipper of superposed
CC beta-strands. Disease mutations may favor intermolecular contacts via
CC short beta strands, and may thereby trigger oligomerization. In
CC addition, the heparan-sulfate proteoglycan, GPC1, promotes the
CC association of PRPN (C) to lipid rafts and appears to facilitate the
CC conversion to PRPN (Sc). {ECO:0000269|PubMed:17468747,
CC ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:20564047}.
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:0000269|PubMed:11524679,
CC ECO:0000269|PubMed:11900542, ECO:0000269|PubMed:20375014}.
CC -!- PTM: The glycosylation pattern (the amount of mono-, di- and non-
CC glycosylated forms or glycoforms) seems to differ in normal and CJD
CC prion. {ECO:0000269|PubMed:12214108}.
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. {ECO:0000269|PubMed:1683708}.
CC -!- POLYMORPHISM: A number of polymorphisms confer resistance to prion
CC diseases (PubMed:1439789, PubMed:9482303, PubMed:19923577,
CC PubMed:26061765). Val-127 has been selected for in response to the Kuru
CC epidemic and confers resistance to prion disease by acting as a
CC 'dominant negative' inhibitor of prion conversion (PubMed:26061765).
CC Val-127 is not only itself resistant to conformational conversion, but
CC also inhibits conversion of wild-type proteins. Confers protection
CC against classical Creutzfeldt-Jakob disease (CJD) and Kuru in the
CC heterozygous state, but can be infected with variant CJD prions,
CC resulting from exposure to bovine spongiform encephalopathy prions.
CC Confers complete resistance to all prion strains when homozygous
CC (PubMed:26061765). Always associated with M-129 variant
CC (PubMed:26061765). Val-129 confers relative protection against
CC acquired, sporadic and some inherited prion diseases in the
CC heterozygous state, possibly by preventing homodimerization
CC (PubMed:1439789). Lys-219 confers relative protection against sporadic
CC Creutzfeldt-Jakob disease (CJD) in the heterozygous state
CC (PubMed:9482303). {ECO:0000269|PubMed:1439789,
CC ECO:0000269|PubMed:26061765, ECO:0000269|PubMed:9482303}.
CC -!- DISEASE: Note=PrP is found in high quantity in the brain of humans and
CC animals infected with neurodegenerative diseases known as transmissible
CC spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob
CC disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler
CC disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in
CC humans; scrapie in sheep and goat; bovine spongiform encephalopathy
CC (BSE) in cattle; transmissible mink encephalopathy (TME); chronic
CC wasting disease (CWD) of mule deer and elk; feline spongiform
CC encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE)
CC in nyala and greater kudu. The prion diseases illustrate three
CC manifestations of CNS degeneration: (1) infectious (2) sporadic and (3)
CC dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to
CC occur after consumption of prion-infected foodstuffs.
CC {ECO:0000269|PubMed:8105771}.
CC -!- DISEASE: Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs primarily
CC as a sporadic disorder (1 per million), while 10-15% are familial.
CC Accidental transmission of CJD to humans appears to be iatrogenic
CC (contaminated human growth hormone (HGH), corneal transplantation,
CC electroencephalographic electrode implantation, etc.). Epidemiologic
CC studies have failed to implicate the ingestion of infected animal meat
CC in the pathogenesis of CJD in human. The triad of microscopic features
CC that characterize the prion diseases consists of (1) spongiform
CC degeneration of neurons, (2) severe astrocytic gliosis that often
CC appears to be out of proportion to the degree of nerve cell loss, and
CC (3) amyloid plaque formation. CJD is characterized by progressive
CC dementia and myoclonic seizures, affecting adults in mid-life. Some
CC patients present sleep disorders, abnormalities of high cortical
CC function, cerebellar and corticospinal disturbances. The disease ends
CC in death after a 3-12 months illness. {ECO:0000269|PubMed:10790216,
CC ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440,
CC ECO:0000269|PubMed:1975028, ECO:0000269|PubMed:19927125,
CC ECO:0000269|PubMed:7902693, ECO:0000269|PubMed:7906019,
CC ECO:0000269|PubMed:7913755, ECO:0000269|PubMed:8461023,
CC ECO:0000269|PubMed:8909447}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Fatal familial insomnia (FFI) [MIM:600072]: Autosomal dominant
CC disorder and is characterized by neuronal degeneration limited to
CC selected thalamic nuclei and progressive insomnia.
CC {ECO:0000269|PubMed:1347910, ECO:0000269|PubMed:1439789,
CC ECO:0000269|PubMed:19927125}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Gerstmann-Straussler disease (GSD) [MIM:137440]: A rare
CC inherited prion disease characterized by adult onset of memory loss,
CC dementia, ataxia, and pathologic deposition of amyloid-like plaques in
CC the brain. GSD presents with progressive limb and truncal ataxia,
CC dysarthria, and cognitive decline in the thirties and forties, and the
CC average disease duration is 7 years. {ECO:0000269|PubMed:10581485,
CC ECO:0000269|PubMed:11709001, ECO:0000269|PubMed:1363810,
CC ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:19927125,
CC ECO:0000269|PubMed:2564168, ECO:0000269|PubMed:7699395,
CC ECO:0000269|PubMed:7783876, ECO:0000269|PubMed:7902972,
CC ECO:0000269|PubMed:8797472, ECO:0000269|PubMed:9786248}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Huntington disease-like 1 (HDL1) [MIM:603218]: Autosomal
CC dominant, early-onset neurodegenerative disorder with prominent
CC psychiatric features. {ECO:0000269|PubMed:9792871}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Kuru (KURU) [MIM:245300]: Kuru is transmitted during
CC ritualistic cannibalism, among natives of the New Guinea highlands.
CC Patients exhibit various movement disorders like cerebellar
CC abnormalities, rigidity of the limbs, and clonus. Emotional lability is
CC present, and dementia is conspicuously absent. Death usually occurs
CC from 3 to 12 month after onset. {ECO:0000269|PubMed:19923577,
CC ECO:0000269|PubMed:26061765}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Spongiform encephalopathy with neuropsychiatric features
CC (SENF) [MIM:606688]: Autosomal dominant presenile dementia with a
CC rapidly progressive and protracted clinical course. The dementia was
CC characterized clinically by frontotemporal features, including early
CC personality changes. Some patients had memory loss, several showed
CC aggressiveness, hyperorality and verbal stereotypy, others had
CC parkinsonian symptoms. {ECO:0000269|PubMed:12214108,
CC ECO:0000269|PubMed:9266722}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the alternative prion protein/AltPrP (AC F7VJQ1) from an
CC overlapping reading frame. {ECO:0000305|PubMed:21478263}.
CC -!- MISCELLANEOUS: The alternative prion protein/AltPrP (AC F7VJQ1) and
CC PRNP have no apparent direct functional relation since a mutation that
CC removes the start codon of the AltPrP has no apparent effect on the
CC biology of PRNP. In mouse and hamster, the alternative initiation AUG
CC codon is absent and is replaced by a GUG codon. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}.
CC -!- CAUTION: An isoform was shown to be localized to both the cytoplasm and
CC the nucleus and to be sumoylated with SUMO1 (PubMed:19059915). The
CC article has later been withdrawn by the authors.
CC {ECO:0000269|PubMed:19059915, ECO:0000305|PubMed:29222195}.
CC -!- WEB RESOURCE: Name=The Official Mad Cow Disease Home Page;
CC URL="http://www.mad-cow.org/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=PRNP entry;
CC URL="https://en.wikipedia.org/wiki/PRNP";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The shape of harm - Issue
CC 179 of May 2016;
CC URL="https://web.expasy.org/spotlight/back_issues/179/";
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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; -; NOT_ANNOTATED_CDS; 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 CCDS; CCDS13080.1; -. [P04156-1]
DR PIR; A24173; UJHU.
DR RefSeq; NP_000302.1; NM_000311.4. [P04156-1]
DR RefSeq; NP_001073590.1; NM_001080121.2. [P04156-1]
DR RefSeq; NP_001073591.1; NM_001080122.2. [P04156-1]
DR RefSeq; NP_001073592.1; NM_001080123.2. [P04156-1]
DR RefSeq; NP_001258490.1; NM_001271561.2.
DR RefSeq; NP_898902.1; NM_183079.3. [P04156-1]
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=77-84.
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; 2M8T; 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 PDB; 4DGI; X-ray; 2.40 A; A=120-230.
DR PDB; 4E1H; X-ray; 1.40 A; A/C/E/G/I/K=177-182, B/D/F/H/J/L=211-216.
DR PDB; 4E1I; X-ray; 2.03 A; A/C/E/G/I/K=177-182, B/D/F/H/J/L=211-216.
DR PDB; 4KML; X-ray; 1.50 A; A=24-231.
DR PDB; 4N9O; X-ray; 1.50 A; A=90-231.
DR PDB; 5L6R; NMR; -; A=90-226.
DR PDB; 5YJ4; NMR; -; A=91-231.
DR PDB; 5YJ5; NMR; -; A=91-231.
DR PDB; 6DU9; X-ray; 2.33 A; A=90-230.
DR PDB; 6LNI; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J=23-231.
DR PDB; 6PQ5; X-ray; 1.50 A; A/B=113-118.
DR PDB; 6PQA; X-ray; 1.46 A; A=119-124.
DR PDB; 6SUZ; X-ray; 2.50 A; A=125-223.
DR PDB; 6SV2; X-ray; 2.30 A; A=119-231.
DR PDB; 6UUR; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=94-178.
DR PDB; 7DWV; EM; 3.07 A; A/B/C/D/E/F=23-231.
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; 2M8T; -.
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 PDBsum; 4DGI; -.
DR PDBsum; 4E1H; -.
DR PDBsum; 4E1I; -.
DR PDBsum; 4KML; -.
DR PDBsum; 4N9O; -.
DR PDBsum; 5L6R; -.
DR PDBsum; 5YJ4; -.
DR PDBsum; 5YJ5; -.
DR PDBsum; 6DU9; -.
DR PDBsum; 6LNI; -.
DR PDBsum; 6PQ5; -.
DR PDBsum; 6PQA; -.
DR PDBsum; 6SUZ; -.
DR PDBsum; 6SV2; -.
DR PDBsum; 6UUR; -.
DR PDBsum; 7DWV; -.
DR AlphaFoldDB; P04156; -.
DR BMRB; P04156; -.
DR SASBDB; P04156; -.
DR SMR; P04156; -.
DR BioGRID; 111606; 443.
DR CORUM; P04156; -.
DR DIP; DIP-29933N; -.
DR ELM; P04156; -.
DR IntAct; P04156; 443.
DR MINT; P04156; -.
DR STRING; 9606.ENSP00000368752; -.
DR BindingDB; P04156; -.
DR ChEMBL; CHEMBL4869; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00759; Tetracycline.
DR DrugCentral; P04156; -.
DR MoonDB; P04156; Predicted.
DR TCDB; 1.C.48.1.2; the prion peptide (prp) family.
DR GlyConnect; 2056; 3 N-Linked glycans (1 site).
DR GlyGen; P04156; 2 sites, 6 N-linked glycans (1 site).
DR iPTMnet; P04156; -.
DR MetOSite; P04156; -.
DR PhosphoSitePlus; P04156; -.
DR SwissPalm; P04156; -.
DR BioMuta; PRNP; -.
DR DMDM; 130912; -.
DR EPD; P04156; -.
DR jPOST; P04156; -.
DR MassIVE; P04156; -.
DR PaxDb; P04156; -.
DR PeptideAtlas; P04156; -.
DR PRIDE; P04156; -.
DR ProteomicsDB; 51667; -. [P04156-1]
DR ABCD; P04156; 3 sequenced antibodies.
DR Antibodypedia; 3351; 656 antibodies from 47 providers.
DR DNASU; 5621; -.
DR Ensembl; ENST00000379440.9; ENSP00000368752.4; ENSG00000171867.18. [P04156-1]
DR Ensembl; ENST00000424424.2; ENSP00000411599.2; ENSG00000171867.18. [P04156-1]
DR Ensembl; ENST00000430350.2; ENSP00000399376.2; ENSG00000171867.18. [P04156-1]
DR Ensembl; ENST00000457586.2; ENSP00000415284.2; ENSG00000171867.18. [P04156-1]
DR GeneID; 5621; -.
DR KEGG; hsa:5621; -.
DR MANE-Select; ENST00000379440.9; ENSP00000368752.4; NM_000311.5; NP_000302.1.
DR CTD; 5621; -.
DR DisGeNET; 5621; -.
DR GeneCards; PRNP; -.
DR GeneReviews; PRNP; -.
DR HGNC; HGNC:9449; PRNP.
DR HPA; ENSG00000171867; Low tissue specificity.
DR MalaCards; PRNP; -.
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 OpenTargets; ENSG00000171867; -.
DR Orphanet; 280397; Familial Alzheimer-like prion disease.
DR Orphanet; 466; Fatal familial insomnia.
DR Orphanet; 356; Gerstmann-Straussler-Scheinker syndrome.
DR Orphanet; 157941; Huntington disease-like 1.
DR Orphanet; 282166; Inherited Creutzfeldt-Jakob disease.
DR Orphanet; 454745; Kuru.
DR Orphanet; 397606; PrP systemic amyloidosis.
DR Orphanet; 586130; Sporadic fatal insomnia.
DR PharmGKB; PA33796; -.
DR VEuPathDB; HostDB:ENSG00000171867; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR GeneTree; ENSGT00510000049083; -.
DR InParanoid; P04156; -.
DR OMA; HNPGYPH; -.
DR OrthoDB; 957343at2759; -.
DR PhylomeDB; P04156; -.
DR TreeFam; TF105188; -.
DR PathwayCommons; P04156; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR SignaLink; P04156; -.
DR BioGRID-ORCS; 5621; 10 hits in 1089 CRISPR screens.
DR ChiTaRS; PRNP; human.
DR EvolutionaryTrace; P04156; -.
DR GenomeRNAi; 5621; -.
DR Pharos; P04156; Tchem.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P04156; protein.
DR Bgee; ENSG00000171867; Expressed in Brodmann (1909) area 23 and 207 other tissues.
DR ExpressionAtlas; P04156; baseline and differential.
DR Genevisible; P04156; HS.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; NAS:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; TAS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016234; C:inclusion body; IMP:CAFA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0045121; C:membrane raft; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; TAS:ARUK-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISS:ARUK-UCL.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; ISS:ARUK-UCL.
DR GO; GO:0043008; F:ATP-dependent protein binding; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB.
DR GO; GO:1903135; F:cupric ion binding; IEA:Ensembl.
DR GO; GO:1903136; F:cuprous ion binding; IMP:CAFA.
DR GO; GO:0005539; F:glycosaminoglycan binding; ISS:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005521; F:lamin binding; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISS:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; ISS:ARUK-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl.
DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IPI:ARUK-UCL.
DR GO; GO:0032147; P:activation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IGI:ARUK-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006878; P:cellular copper ion homeostasis; NAS:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR GO; GO:0071280; P:cellular response to copper ion; IDA:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0097062; P:dendritic spine maintenance; TAS:ARUK-UCL.
DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL.
DR GO; GO:0007616; P:long-term memory; TAS:ARUK-UCL.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:BHF-UCL.
DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; ISS:ARUK-UCL.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:BHF-UCL.
DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; ISS:ARUK-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; 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:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:BHF-UCL.
DR GO; GO:0010955; P:negative regulation of protein processing; TAS:ARUK-UCL.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:1990535; P:neuron projection maintenance; ISS:ARUK-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:CAFA.
DR GO; GO:1901216; P:positive regulation of neuron death; ISS:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:ARUK-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IGI:ARUK-UCL.
DR GO; GO:0031648; P:protein destabilization; IMP:CAFA.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IGI:ARUK-UCL.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:1904645; P:response to amyloid-beta; ISS:ARUK-UCL.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR DisProt; DP00466; -.
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; Alternative initiation; Amyloid; Amyloidosis; Cell cycle;
KW Cell membrane; Copper; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor; Growth arrest;
KW Lipoprotein; Membrane; Metal-binding; Prion; Reference proteome; Repeat;
KW Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT CHAIN 23..230
FT /note="Major prion protein"
FT /id="PRO_0000025675"
FT PROPEP 231..253
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT /id="PRO_0000025676"
FT REPEAT 51..59
FT /note="1"
FT REPEAT 60..67
FT /note="2"
FT REPEAT 68..75
FT /note="3"
FT REPEAT 76..83
FT /note="4"
FT REPEAT 84..91
FT /note="5"
FT REGION 23..230
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 23..38
FT /note="Interaction with ADGRG6"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 26..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..91
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 61
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11900542"
FT BINDING 62
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11900542"
FT BINDING 63
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11900542"
FT BINDING 69
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 70
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 71
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 77
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 78
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 79
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 85
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 86
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000305|PubMed:11900542"
FT BINDING 87
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000305|PubMed:11900542"
FT LIPID 230
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000250|UniProtKB:P04273"
FT CARBOHYD 181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12214108"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 179..214
FT /evidence="ECO:0000269|PubMed:14623188"
FT VARIANT 56..63
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:1363802,
FT ECO:0000269|PubMed:1678248, ECO:0000269|PubMed:7485229"
FT /id="VAR_013763"
FT VARIANT 102
FT /note="P -> L (in GSD and early-onset dementia;
FT dbSNP:rs74315401)"
FT /evidence="ECO:0000269|PubMed:10631141,
FT ECO:0000269|PubMed:2564168, ECO:0000269|PubMed:2783132,
FT ECO:0000269|PubMed:7783876, ECO:0000269|PubMed:8797472"
FT /id="VAR_006464"
FT VARIANT 105
FT /note="P -> L (in GSD; dbSNP:rs11538758)"
FT /evidence="ECO:0000269|PubMed:7699395,
FT ECO:0000269|PubMed:7902972"
FT /id="VAR_006465"
FT VARIANT 117
FT /note="A -> V (linked to development of dementing
FT Gerstmann-Straussler disease; dbSNP:rs74315402)"
FT /evidence="ECO:0000269|PubMed:2783132"
FT /id="VAR_006466"
FT VARIANT 127
FT /note="G -> V (variant that has been selected for in
FT response to the Kuru epidemic and confers resistance to
FT prion disease by acting as a 'dominant negative' inhibitor
FT of prion conversion; is not only itself resistant to
FT conformational conversion, but also inhibits conversion of
FT wild-type proteins; confers protection against classical
FT Creutzfeldt-Jakob disease (CJD) and Kuru in the
FT heterozygous state, but can be infected with variant CJD
FT prions, resulting from exposure to bovine spongiform
FT encephalopathy prions; confers complete resistance to all
FT prion strains when homozygous. Always associated with M-129
FT variant; dbSNP:rs267606980)"
FT /evidence="ECO:0000269|PubMed:19923577,
FT ECO:0000269|PubMed:26061765"
FT /id="VAR_073722"
FT VARIANT 129
FT /note="M -> V (confers relative protection against
FT acquired, sporadic and some inherited prion diseases in the
FT heterozygous state, possibly by preventing
FT homodimerization; determines the disease phenotype in
FT patients who have a PrP mutation at position 178; patients
FT with M-129 develop FFI, those with V-129 develop CJD;
FT dbSNP:rs1799990)"
FT /evidence="ECO:0000269|PubMed:12690204,
FT ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:19927125,
FT ECO:0000269|PubMed:2783132"
FT /id="VAR_006467"
FT VARIANT 131
FT /note="G -> V (in GSD; dbSNP:rs74315410)"
FT /evidence="ECO:0000269|PubMed:11709001"
FT /id="VAR_014264"
FT VARIANT 171
FT /note="N -> S (in schizoaffective disorder;
FT dbSNP:rs16990018)"
FT /evidence="ECO:0000269|PubMed:9384372"
FT /id="VAR_006468"
FT VARIANT 178
FT /note="D -> N (in FFI and CJD; dbSNP:rs74315403)"
FT /evidence="ECO:0000269|PubMed:1347910,
FT ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440,
FT ECO:0000269|PubMed:19927125"
FT /id="VAR_006469"
FT VARIANT 180
FT /note="V -> I (in CJD; dbSNP:rs74315408)"
FT /evidence="ECO:0000269|PubMed:1439789,
FT ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:8461023"
FT /id="VAR_006470"
FT VARIANT 183
FT /note="T -> A (in SENF and early-onset dementia; induces
FT loss of glycosylation at N-181; dbSNP:rs74315411)"
FT /evidence="ECO:0000269|PubMed:10631141,
FT ECO:0000269|PubMed:12214108, ECO:0000269|PubMed:9266722"
FT /id="VAR_006471"
FT VARIANT 187
FT /note="H -> R (in GSD; dbSNP:rs74315413)"
FT /evidence="ECO:0000269|PubMed:10581485"
FT /id="VAR_008746"
FT VARIANT 188
FT /note="T -> K (in early-onset dementia; dementia associated
FT to prion diseases)"
FT /evidence="ECO:0000269|PubMed:10631141"
FT /id="VAR_008748"
FT VARIANT 188
FT /note="T -> R (in dbSNP:rs372878791)"
FT /evidence="ECO:0000269|PubMed:10987652"
FT /id="VAR_008747"
FT VARIANT 196
FT /note="E -> K (in CJD)"
FT /evidence="ECO:0000269|PubMed:10790216"
FT /id="VAR_008749"
FT VARIANT 198
FT /note="F -> S (in GSD; atypical form with neurofibrillary
FT tangles; dbSNP:rs74315405)"
FT /evidence="ECO:0000269|PubMed:19927125"
FT /id="VAR_006472"
FT VARIANT 200
FT /note="E -> K (in CJD; dbSNP:rs28933385)"
FT /evidence="ECO:0000269|PubMed:1975028,
FT ECO:0000269|PubMed:7906019, ECO:0000269|PubMed:7913755"
FT /id="VAR_006473"
FT VARIANT 202
FT /note="D -> N (in GSD; dbSNP:rs761807915)"
FT /evidence="ECO:0000269|PubMed:9786248"
FT /id="VAR_008750"
FT VARIANT 203
FT /note="V -> I (in CJD; unknown pathological significance;
FT dbSNP:rs776593792)"
FT /evidence="ECO:0000269|PubMed:10790216"
FT /id="VAR_008751"
FT VARIANT 208
FT /note="R -> H (in CJD; dbSNP:rs74315412)"
FT /evidence="ECO:0000269|PubMed:8909447"
FT /id="VAR_006474"
FT VARIANT 210
FT /note="V -> I (in CJD; dbSNP:rs74315407)"
FT /evidence="ECO:0000269|PubMed:7902693"
FT /id="VAR_006475"
FT VARIANT 211
FT /note="E -> Q (in CJD; dbSNP:rs398122370)"
FT /evidence="ECO:0000269|PubMed:10790216"
FT /id="VAR_008752"
FT VARIANT 212
FT /note="Q -> P (in GSD; dbSNP:rs751882709)"
FT /evidence="ECO:0000269|PubMed:9786248"
FT /id="VAR_008753"
FT VARIANT 217
FT /note="Q -> R (in GSD; with neurofibrillary tangles;
FT dbSNP:rs74315406)"
FT /evidence="ECO:0000269|PubMed:1363810"
FT /id="VAR_006476"
FT VARIANT 219
FT /note="E -> K (confers relative protection against sporadic
FT Creutzfeldt-Jakob disease (CJD) in the heterozygous state;
FT dbSNP:rs1800014)"
FT /evidence="ECO:0000269|PubMed:8797472,
FT ECO:0000269|PubMed:9482303"
FT /id="VAR_006477"
FT VARIANT 232
FT /note="M -> R (in CJD; dbSNP:rs74315409)"
FT /evidence="ECO:0000269|PubMed:8461023"
FT /id="VAR_006478"
FT VARIANT 238
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:10987652"
FT /id="VAR_008754"
FT CONFLICT 118
FT /note="Missing (in Ref. 9; AAA19664/BAA00011)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="Y -> H (in Ref. 6; ABD63004)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="Q -> K (in Ref. 8; AAH22532)"
FT /evidence="ECO:0000305"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1OEI"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:1OEI"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:1OEI"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1OEH"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:5YJ4"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:5L6R"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:4KML"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:1H0L"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:3MD4"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6UUR"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:6UUR"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:1E1S"
FT HELIX 144..153
FT /evidence="ECO:0007829|PDB:4KML"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:4KML"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:1E1U"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:4KML"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:1QM0"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:4E1H"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:6LNI"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:6LNI"
FT TURN 193..195
FT /evidence="ECO:0007829|PDB:3HAK"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:6LNI"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:6LNI"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:4E1H"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:3HER"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:2LFT"
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
