ID PRIO_BOVIN Reviewed; 264 AA. AC P10279; A1YVV9; Q01880; Q0VD57; Q5UJJ5; Q5UJM6; Q5UK69; Q5UK71; Q6UL03; AC Q6UL04; Q6UL05; Q6UL06; Q7YRN3; Q8MJI7; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1991, sequence version 2. DT 24-JAN-2024, entry version 216. DE RecName: Full=Major prion protein; DE Short=PrP; DE AltName: Full=Major scrapie-associated fibril protein 1; DE AltName: CD_antigen=CD230; DE Flags: Precursor; GN Name=PRNP; Synonyms=PRP; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Holstein-Friesian; RX PubMed=1671225; DOI=10.1099/0022-1317-72-1-201; RA Goldmann W., Hunter N., Martin T., Dawson M., Hope J.; RT "Different forms of the bovine PrP gene have five or six copies of a short, RT G-C-rich element within the protein-coding exon."; RL J. Gen. Virol. 72:201-204(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS 92-TRP--GLY-99 DEL RP AND ASN-154. RC STRAIN=Holstein-Friesian; TISSUE=Brain; RX PubMed=1362024; DOI=10.1007/bf01703083; RA Yoshimoto J., Iinuma T., Ishiguro N., Horiuchi M., Imamura M., RA Shinagawa M.; RT "Comparative sequence analysis and expression of bovine PrP gene in mouse RT L-929 cells."; RL Virus Genes 6:343-356(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8440932; DOI=10.1093/infdis/167.3.602; RA Prusiner S.B., Fuzi M., Scott M., Serban D., Serban H., Taraboulos A., RA Gabriel J.M., Wells G.A., Wilesmith J.W., Bradley R.; RT "Immunologic and molecular biologic studies of prion proteins in bovine RT spongiform encephalopathy."; RL J. Infect. Dis. 167:602-613(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Holstein-Friesian; TISSUE=Brain; RA Horiuchi M., Ishiguro N., Nagasawa H., Toyoda Y., Shinagawa M.; RT "Genomic organization of bovine PrP gene and complete nucleotide sequence RT of bovine PrP cDNA."; RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Jersey; RX PubMed=11531705; DOI=10.1046/j.1365-2052.2001.0769a.x; RA Hills D., Comincini S., Schlaepfer J., Dolf G., Ferretti L., Williams J.L.; RT "Complete genomic sequence of the bovine prion gene (PRNP) and polymorphism RT in its promoter region."; RL Anim. Genet. 32:231-232(2001). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT RP GLY-TRP-GLY-GLN-PRO-HIS-GLY-GLY-98 INS. RA Naharro G., Yugueros J., Temprano A.; RT "Bovine PrP gene for prion protein."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Korean; RA Yoo H.S., Kang S.G., Choi I.S., Kang S.K., Hwang W.S.; RT "Nucleotide sequence of PrP cDNA in Korean cattle."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=14722726; DOI=10.1007/s00335-003-2283-y; RA Heaton M.P., Leymaster K.A., Freking B.A., Hawk D.A., Smith T.P., RA Keele J.W., Snelling W.M., Fox J.M., Chitko-McKown C.G., Laegreid W.W.; RT "Prion gene sequence variation within diverse groups of U.S. sheep, beef RT cattle, and deer."; RL Mamm. Genome 14:765-777(2003). RN [9] RP SEQUENCE REVISION TO 211, AND VARIANT LYS-211. RX PubMed=18625065; DOI=10.1186/1746-6148-4-25; RA Heaton M.P., Keele J.W., Harhay G.P., Richt J.A., Koohmaraie M., RA Wheeler T.L., Shackelford S.D., Casas E., King D.A., Sonstegard T.S., RA Van Tassell C.P., Neibergs H.L., Chase C.C. Jr., Kalbfleisch T.S., RA Smith T.P.L., Clawson M.L., Laegreid W.W.; RT "Prevalence of the prion protein gene E211K variant in U.S. cattle."; RL BMC Vet. Res. 4:25-25(2008). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-60; ARG-94; ASN-154 AND RP ARG-234. RC STRAIN=Holstein-Friesian, and Qinchuan; TISSUE=Blood; RA Wu R., Xie Q.G., Liu X.T., Chen H.T., Cheng J.; RT "Cloning and sequence analysis of bovine prion protein gene."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS 84-TRP--GLY-99 DEL; RP 92-TRP--GLY-99 DEL AND GLY-TRP-GLY-GLN-PRO-HIS-GLY-GLY-98 INS. RX PubMed=15477588; DOI=10.1073/pnas.0406403101; RA Seabury C.M., Honeycutt R.L., Rooney A.P., Halbert N.D., Derr J.N.; RT "Prion protein gene (PRNP) variants and evidence for strong purifying RT selection in functionally important regions of bovine exon 3."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15142-15147(2004). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Uboldi C., Bertoni A., Del Vecchio I., Comincini S., Hills D., RA Schlaepfer J., Dolf G., Williams J.L., Ferretti L.; RT "Genomic characterization of the bovine PRN loci (PRNP, PRND and PRNT)."; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=16460908; DOI=10.1016/j.ygeno.2005.12.012; RA Choi S.-H., Kim I.-C., Kim D.-S., Kim D.-W., Chae S.-H., Choi H.-H., RA Choi I., Yeo J.-S., Song M.-N., Park H.-S.; RT "Comparative genomic organization of the human and bovine PRNP locus."; RL Genomics 87:598-607(2006). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Holstein, and Japanese black; TISSUE=Semen; RA Abe T., Hasebe H., Kobayashi E.; RT "Frequencies of bovine PrP gene polymorphisms in Japanese-black and RT Holstein bulls in japan."; RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Brain; RA Barbieri I., Brocchi E., Borre A., Moretti M., Gelmetti D., Capucci L.; RT "Detection of prion protein in various animal species by a new set of RT monoclonal antibodies."; RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases. RN [16] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Hypothalamus; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases. RN [17] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15. RA Tanaka M., Inoue S., Ikeda T., Horiuchi M., Ishiguro N., Shinagawa M.; RT "Characterization of bovine PrP promoter region."; RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases. RN [18] RP PROTEIN SEQUENCE OF 25-36. RX PubMed=2904126; DOI=10.1038/336390a0; RA Hope J., Reekie L.J.D., Hunter N., Multhaup G., Beyreuther K., White H., RA Scott A.C., Stack M.J., Dawson M., Wells G.A.; RT "Fibrils from brains of cows with new cattle disease contain scrapie- RT associated protein."; RL Nature 336:390-392(1988). RN [19] RP STRUCTURE BY NMR OF 1-30. RX PubMed=15554701; DOI=10.1021/bi0485070; RA Biverstahl H., Andersson A., Graslund A., Maler L.; RT "NMR solution structure and membrane interaction of the N-terminal sequence RT (1-30) of the bovine prion protein."; RL Biochemistry 43:14940-14947(2004). RN [20] RP STRUCTURE BY NMR OF 132-241. RX PubMed=10899999; DOI=10.1073/pnas.97.15.8334; RA Lopez Garcia F., Zahn R., Riek R., Wuethrich K.; RT "NMR structure of the bovine prion protein."; RL Proc. Natl. Acad. Sci. U.S.A. 97:8334-8339(2000). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 107-115 IN COMPLEX WITH ANTIBODY RP FRAGMENT. RX PubMed=16962610; DOI=10.1016/j.jmb.2006.07.027; RA Luginbuhl B., Kanyo Z., Jones R.M., Fletterick R.J., Prusiner S.B., RA Cohen F.E., Williamson R.A., Burton D.R., Pluckthun A.; RT "Directed evolution of an anti-prion protein scFv fragment to an affinity RT of 1 pM and its structural interpretation."; RL J. Mol. Biol. 363:75-97(2006). CC -!- FUNCTION: Its primary physiological function is unclear. May play a CC role in neuronal development and synaptic plasticity. May be required CC for neuronal myelin sheath maintenance. May promote myelin homeostasis CC through acting as an agonist for ADGRG6 receptor. May play a role in CC iron uptake and iron homeostasis. Soluble oligomers are toxic to CC cultured neuroblastoma cells and induce apoptosis (in vitro) (By CC similarity). Association with GPC1 (via its heparan sulfate chains) CC targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the CC ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate CC side chains (By similarity). {ECO:0000250|UniProtKB:P04156, CC ECO:0000250|UniProtKB:P04925}. CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into CC amyloid fibrils containing a cross-beta spine, formed by a steric CC zipper of superposed beta-strands. Soluble oligomers may represent an CC intermediate stage on the path to fibril formation. Copper binding may CC promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1 CC (By similarity). Mislocalized cytosolically exposed PrP interacts with CC MGRN1; this interaction alters MGRN1 subcellular location and causes CC lysosomal enlargement (By similarity). Interacts with APP. Interacts CC with KIAA1191 (By similarity). Interacts with ADGRG6 (By similarity). CC {ECO:0000250|UniProtKB:P04156, ECO:0000250|UniProtKB:P04925}. CC -!- INTERACTION: CC P10279; P10279: PRNP; NbExp=3; IntAct=EBI-7430632, EBI-7430632; CC P10279; P04156: PRNP; Xeno; NbExp=5; IntAct=EBI-7430632, EBI-977302; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04156}; CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:P04156}. Golgi CC apparatus {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts CC via association with the heparan sulfate chains of GPC1. Colocates, in CC the presence of Cu(2+), to vesicles in para- and perinuclear regions, CC where both proteins undergo internalization. Heparin displaces PRNP CC from lipid rafts and promotes endocytosis. CC {ECO:0000250|UniProtKB:P04156}. CC -!- DOMAIN: The normal, monomeric form has a mainly alpha-helical CC structure. The disease-associated, protease-resistant form forms CC amyloid fibrils containing a cross-beta spine, formed by a steric CC zipper of superposed beta-strands. Disease mutations may favor CC intermolecular contacts via short beta strands, and may thereby trigger CC oligomerization. {ECO:0000250|UniProtKB:P04156}. CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. At CC low copper concentrations, the sidechains of His residues from three or CC four repeats contribute to the binding of a single copper ion. CC Alternatively, a copper ion can be bound by interaction with the CC sidechain and backbone amide nitrogen of a single His residue. The CC observed copper binding stoichiometry suggests that two repeat regions CC cooperate to stabilize the binding of a single copper ion. At higher CC copper concentrations, each octamer can bind one copper ion by CC interactions with the His sidechain and Gly backbone atoms. A mixture CC of binding types may occur, especially in the case of octamer repeat CC expansion. Copper binding may stabilize the conformation of this region CC and may promote oligomerization. {ECO:0000250|UniProtKB:P04156}. CC -!- DISEASE: Note=Variations in PRNP are responsible of transmissible CC bovine spongiform encephalopathies (BSE), a class of neurodegenerative CC diseases that affect various mammals. These diseases are caused by CC abnormally folded prion proteins. BSE can be subdivided into at least CC three groups: classical, H-type and L-type, with the latter 2 CC collectively referred to as atypical BSE. Susceptibility or resistance CC to a BSE disease can be influenced by at least 3 factors related to the CC host prion protein: protein expression levels, number of octapeptide CC repeats, and specific polymorphisms. In cattle, as in humans, BSEs can CC occur as infectious, spontaneous and genetic diseases. {ECO:0000305}. CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which CC also produces the major prion protein/PRNP from an overlapping reading CC frame. CC -!- MISCELLANEOUS: The alternative prion protein/AltPrP (AC F7VJQ2) 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 (By similarity). In mouse and hamster, the alternative CC initiation AUG codon is absent and is replaced by a GUG codon. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X55882; CAA39368.1; -; Genomic_DNA. DR EMBL; D10612; BAA01467.1; -; mRNA. DR EMBL; D10613; BAA01468.1; -; Genomic_DNA. DR EMBL; D10614; BAA01469.1; -; Genomic_DNA. DR EMBL; S55629; AAB25514.1; -; mRNA. DR EMBL; AB001468; BAA19253.1; -; mRNA. DR EMBL; AJ298878; CAC37367.1; -; Genomic_DNA. DR EMBL; AF455119; AAM73856.1; -; Genomic_DNA. DR EMBL; AF517842; AAM66709.1; -; mRNA. DR EMBL; AY335912; AAP84097.2; -; Genomic_DNA. DR EMBL; AY367638; AAQ64645.1; -; Genomic_DNA. DR EMBL; AY367639; AAQ64646.1; -; Genomic_DNA. DR EMBL; AY367640; AAQ64647.1; -; Genomic_DNA. DR EMBL; AY367641; AAQ64648.1; -; Genomic_DNA. DR EMBL; AY367642; AAQ64649.1; -; Genomic_DNA. DR EMBL; AY367643; AAQ64650.1; -; Genomic_DNA. DR EMBL; AY720445; AAV30252.1; -; Genomic_DNA. DR EMBL; AY720446; AAV30253.1; -; Genomic_DNA. DR EMBL; AY720448; AAV30255.1; -; Genomic_DNA. DR EMBL; AY720449; AAV30256.1; -; Genomic_DNA. DR EMBL; AY720450; AAV30257.1; -; Genomic_DNA. DR EMBL; AY720451; AAV30258.1; -; Genomic_DNA. DR EMBL; AY720452; AAV30259.1; -; Genomic_DNA. DR EMBL; AY720453; AAV30260.1; -; Genomic_DNA. DR EMBL; AY720454; AAV30261.1; -; Genomic_DNA. DR EMBL; AY720455; AAV30262.1; -; Genomic_DNA. DR EMBL; AY720458; AAV30265.1; -; Genomic_DNA. DR EMBL; AY720459; AAV30266.1; -; Genomic_DNA. DR EMBL; AY720460; AAV30267.1; -; Genomic_DNA. DR EMBL; AY720461; AAV30268.1; -; Genomic_DNA. DR EMBL; AY720462; AAV30269.1; -; Genomic_DNA. DR EMBL; AY720463; AAV30270.1; -; Genomic_DNA. DR EMBL; AY720464; AAV30271.1; -; Genomic_DNA. DR EMBL; AY720465; AAV30272.1; -; Genomic_DNA. DR EMBL; AY720466; AAV30273.1; -; Genomic_DNA. DR EMBL; AY720467; AAV30274.1; -; Genomic_DNA. DR EMBL; AY720468; AAV30275.1; -; Genomic_DNA. DR EMBL; AY720469; AAV30276.1; -; Genomic_DNA. DR EMBL; AY720470; AAV30277.1; -; Genomic_DNA. DR EMBL; AY720471; AAV30278.1; -; Genomic_DNA. DR EMBL; AY720472; AAV30279.1; -; Genomic_DNA. DR EMBL; AY720473; AAV30280.1; -; Genomic_DNA. DR EMBL; AY720474; AAV30281.1; -; Genomic_DNA. DR EMBL; AY720475; AAV30282.1; -; Genomic_DNA. DR EMBL; AY720476; AAV30283.1; -; Genomic_DNA. DR EMBL; AY720477; AAV30284.1; -; Genomic_DNA. DR EMBL; AY720478; AAV30285.1; -; Genomic_DNA. DR EMBL; AY720479; AAV30286.1; -; Genomic_DNA. DR EMBL; AY720480; AAV30287.1; -; Genomic_DNA. DR EMBL; AY720481; AAV30288.1; -; Genomic_DNA. DR EMBL; AY720482; AAV30289.1; -; Genomic_DNA. DR EMBL; AY720483; AAV30290.1; -; Genomic_DNA. DR EMBL; AY720484; AAV30291.1; -; Genomic_DNA. DR EMBL; AY720485; AAV30292.1; -; Genomic_DNA. DR EMBL; AY720486; AAV30293.1; -; Genomic_DNA. DR EMBL; AY720488; AAV30295.1; -; Genomic_DNA. DR EMBL; AY720489; AAV30296.1; -; Genomic_DNA. DR EMBL; AY720492; AAV30299.1; -; Genomic_DNA. DR EMBL; AY720493; AAV30300.1; -; Genomic_DNA. DR EMBL; AY720494; AAV30301.1; -; Genomic_DNA. DR EMBL; AY720495; AAV30302.1; -; Genomic_DNA. DR EMBL; AY720496; AAV30303.1; -; Genomic_DNA. DR EMBL; AY720497; AAV30304.1; -; Genomic_DNA. DR EMBL; AY720498; AAV30305.1; -; Genomic_DNA. DR EMBL; AY720503; AAV30310.1; -; Genomic_DNA. DR EMBL; AY720504; AAV30311.1; -; Genomic_DNA. DR EMBL; AY720505; AAV30312.1; -; Genomic_DNA. DR EMBL; AY720506; AAV30313.1; -; Genomic_DNA. DR EMBL; AY720507; AAV30314.1; -; Genomic_DNA. DR EMBL; AY720508; AAV30315.1; -; Genomic_DNA. DR EMBL; AY720509; AAV30316.1; -; Genomic_DNA. DR EMBL; AY720510; AAV30317.1; -; Genomic_DNA. DR EMBL; AY720511; AAV30318.1; -; Genomic_DNA. DR EMBL; AY720512; AAV30319.1; -; Genomic_DNA. DR EMBL; AY720513; AAV30320.1; -; Genomic_DNA. DR EMBL; AY720514; AAV30321.1; -; Genomic_DNA. DR EMBL; AY720525; AAV30332.1; -; Genomic_DNA. DR EMBL; AY720530; AAV30337.1; -; Genomic_DNA. DR EMBL; AY720531; AAV30338.1; -; Genomic_DNA. DR EMBL; AY720532; AAV30339.1; -; Genomic_DNA. DR EMBL; AY720533; AAV30340.1; -; Genomic_DNA. DR EMBL; AY720534; AAV30341.1; -; Genomic_DNA. DR EMBL; AY720535; AAV30342.1; -; Genomic_DNA. DR EMBL; AY720540; AAV30347.1; -; Genomic_DNA. DR EMBL; AY720541; AAV30348.1; -; Genomic_DNA. DR EMBL; AY720544; AAV30351.1; -; Genomic_DNA. DR EMBL; AY720545; AAV30352.1; -; Genomic_DNA. DR EMBL; AY720546; AAV30353.1; -; Genomic_DNA. DR EMBL; AY720547; AAV30354.1; -; Genomic_DNA. DR EMBL; AY720548; AAV30355.1; -; Genomic_DNA. DR EMBL; AY720549; AAV30356.1; -; Genomic_DNA. DR EMBL; AY720550; AAV30357.1; -; Genomic_DNA. DR EMBL; AY720551; AAV30358.1; -; Genomic_DNA. DR EMBL; AY720552; AAV30359.1; -; Genomic_DNA. DR EMBL; AY720553; AAV30360.1; -; Genomic_DNA. DR EMBL; AY720554; AAV30361.1; -; Genomic_DNA. DR EMBL; AY720555; AAV30362.1; -; Genomic_DNA. DR EMBL; AY720556; AAV30363.1; -; Genomic_DNA. DR EMBL; AY720557; AAV30364.1; -; Genomic_DNA. DR EMBL; AY720558; AAV30365.1; -; Genomic_DNA. DR EMBL; AY720559; AAV30366.1; -; Genomic_DNA. DR EMBL; AY720560; AAV30367.1; -; Genomic_DNA. DR EMBL; AY720561; AAV30368.1; -; Genomic_DNA. DR EMBL; AY720562; AAV30369.1; -; Genomic_DNA. DR EMBL; AY720563; AAV30370.1; -; Genomic_DNA. DR EMBL; AY720564; AAV30371.1; -; Genomic_DNA. DR EMBL; AY720565; AAV30372.1; -; Genomic_DNA. DR EMBL; AY720566; AAV30373.1; -; Genomic_DNA. DR EMBL; AY720567; AAV30374.1; -; Genomic_DNA. DR EMBL; AY720568; AAV30375.1; -; Genomic_DNA. DR EMBL; AY720569; AAV30376.1; -; Genomic_DNA. DR EMBL; AY720570; AAV30377.1; -; Genomic_DNA. DR EMBL; AY720571; AAV30378.1; -; Genomic_DNA. DR EMBL; AY720572; AAV30379.1; -; Genomic_DNA. DR EMBL; AY720573; AAV30380.1; -; Genomic_DNA. DR EMBL; AY720574; AAV30381.1; -; Genomic_DNA. DR EMBL; AY720581; AAV30388.1; -; Genomic_DNA. DR EMBL; AY720582; AAV30389.1; -; Genomic_DNA. DR EMBL; AY720583; AAV30390.1; -; Genomic_DNA. DR EMBL; AY720584; AAV30391.1; -; Genomic_DNA. DR EMBL; AY720585; AAV30392.1; -; Genomic_DNA. DR EMBL; AY720588; AAV30395.1; -; Genomic_DNA. DR EMBL; AY720591; AAV30398.1; -; Genomic_DNA. DR EMBL; AY720594; AAV30401.1; -; Genomic_DNA. DR EMBL; AY720595; AAV30402.1; -; Genomic_DNA. DR EMBL; AY720596; AAV30403.1; -; Genomic_DNA. DR EMBL; AY720597; AAV30404.1; -; Genomic_DNA. DR EMBL; AY720600; AAV30407.1; -; Genomic_DNA. DR EMBL; AY720601; AAV30408.1; -; Genomic_DNA. DR EMBL; AY720602; AAV30409.1; -; Genomic_DNA. DR EMBL; AY720603; AAV30410.1; -; Genomic_DNA. DR EMBL; AY720604; AAV30411.1; -; Genomic_DNA. DR EMBL; AY720605; AAV30412.1; -; Genomic_DNA. DR EMBL; AY720606; AAV30413.1; -; Genomic_DNA. DR EMBL; AY720607; AAV30414.1; -; Genomic_DNA. DR EMBL; AY720608; AAV30415.1; -; Genomic_DNA. DR EMBL; AY720609; AAV30416.1; -; Genomic_DNA. DR EMBL; AY720610; AAV30417.1; -; Genomic_DNA. DR EMBL; AY720611; AAV30418.1; -; Genomic_DNA. DR EMBL; AY720612; AAV30419.1; -; Genomic_DNA. DR EMBL; AY720613; AAV30420.1; -; Genomic_DNA. DR EMBL; AY720622; AAV30429.1; -; Genomic_DNA. DR EMBL; AY720623; AAV30430.1; -; Genomic_DNA. DR EMBL; AY720624; AAV30431.1; -; Genomic_DNA. DR EMBL; AY720625; AAV30432.1; -; Genomic_DNA. DR EMBL; AY720626; AAV30433.1; -; Genomic_DNA. DR EMBL; AY720627; AAV30434.1; -; Genomic_DNA. DR EMBL; AY720628; AAV30435.1; -; Genomic_DNA. DR EMBL; AY720629; AAV30436.1; -; Genomic_DNA. DR EMBL; AY720630; AAV30437.1; -; Genomic_DNA. DR EMBL; AY720631; AAV30438.1; -; Genomic_DNA. DR EMBL; AY720632; AAV30439.1; -; Genomic_DNA. DR EMBL; AY720633; AAV30440.1; -; Genomic_DNA. DR EMBL; AY720634; AAV30441.1; -; Genomic_DNA. DR EMBL; AY720635; AAV30442.1; -; Genomic_DNA. DR EMBL; AY720636; AAV30443.1; -; Genomic_DNA. DR EMBL; AY720637; AAV30444.1; -; Genomic_DNA. DR EMBL; AY720640; AAV30447.1; -; Genomic_DNA. DR EMBL; AY720641; AAV30448.1; -; Genomic_DNA. DR EMBL; AY720642; AAV30449.1; -; Genomic_DNA. DR EMBL; AY720643; AAV30450.1; -; Genomic_DNA. DR EMBL; AY720644; AAV30451.1; -; Genomic_DNA. DR EMBL; AY720645; AAV30452.1; -; Genomic_DNA. DR EMBL; AY720648; AAV30455.1; -; Genomic_DNA. DR EMBL; AY720649; AAV30456.1; -; Genomic_DNA. DR EMBL; AY720650; AAV30457.1; -; Genomic_DNA. DR EMBL; AY720651; AAV30458.1; -; Genomic_DNA. DR EMBL; AY720652; AAV30459.1; -; Genomic_DNA. DR EMBL; AY720653; AAV30460.1; -; Genomic_DNA. DR EMBL; AY720654; AAV30461.1; -; Genomic_DNA. DR EMBL; AY720655; AAV30462.1; -; Genomic_DNA. DR EMBL; AY720656; AAV30463.1; -; Genomic_DNA. DR EMBL; AY720657; AAV30464.1; -; Genomic_DNA. DR EMBL; AY720662; AAV30469.1; -; Genomic_DNA. DR EMBL; AY720663; AAV30470.1; -; Genomic_DNA. DR EMBL; AY720664; AAV30471.1; -; Genomic_DNA. DR EMBL; AY720667; AAV30474.1; -; Genomic_DNA. DR EMBL; AY720668; AAV30475.1; -; Genomic_DNA. DR EMBL; AY720669; AAV30476.1; -; Genomic_DNA. DR EMBL; AY720670; AAV30477.1; -; Genomic_DNA. DR EMBL; AY720671; AAV30478.1; -; Genomic_DNA. DR EMBL; AY720672; AAV30479.1; -; Genomic_DNA. DR EMBL; AY720673; AAV30480.1; -; Genomic_DNA. DR EMBL; AY720674; AAV30481.1; -; Genomic_DNA. DR EMBL; AY720675; AAV30482.1; -; Genomic_DNA. DR EMBL; AY720676; AAV30483.1; -; Genomic_DNA. DR EMBL; AY720677; AAV30484.1; -; Genomic_DNA. DR EMBL; AY720678; AAV30485.1; -; Genomic_DNA. DR EMBL; DQ205538; ABB51165.1; -; Genomic_DNA. DR EMBL; AY944236; AAY21624.1; -; Genomic_DNA. DR EMBL; AB248079; BAE78586.1; -; Genomic_DNA. DR EMBL; AB247937; BAE78583.1; -; Genomic_DNA. DR EMBL; EF139165; ABL75501.1; -; Genomic_DNA. DR EMBL; BC119821; AAI19822.1; -; mRNA. DR EMBL; D26151; BAA05138.1; -; Genomic_DNA. DR PIR; A54330; A54330. DR PIR; JU0268; JU0268. DR RefSeq; NP_001258555.1; NM_001271626.2. DR RefSeq; NP_851358.2; NM_181015.3. DR PDB; 1DWY; NMR; -; A=132-241. DR PDB; 1DWZ; NMR; -; A=132-241. DR PDB; 1DX0; NMR; -; A=25-241. DR PDB; 1DX1; NMR; -; A=25-241. DR PDB; 1SKH; NMR; -; A=1-30. DR PDB; 2HH0; X-ray; 2.85 A; P=107-115. DR PDB; 2RSK; NMR; -; C/D=108-119. DR PDB; 2RU7; NMR; -; C/D=108-119. DR PDB; 4YX2; X-ray; 2.19 A; A=103-242. DR PDBsum; 1DWY; -. DR PDBsum; 1DWZ; -. DR PDBsum; 1DX0; -. DR PDBsum; 1DX1; -. DR PDBsum; 1SKH; -. DR PDBsum; 2HH0; -. DR PDBsum; 2RSK; -. DR PDBsum; 2RU7; -. DR PDBsum; 4YX2; -. DR AlphaFoldDB; P10279; -. DR BMRB; P10279; -. DR SMR; P10279; -. DR BioGRID; 158758; 3. DR IntAct; P10279; 1. DR MINT; P10279; -. DR STRING; 9913.ENSBTAP00000069134; -. DR GlyCosmos; P10279; 2 sites, No reported glycans. DR PaxDb; 9913-ENSBTAP00000043233; -. DR ABCD; P10279; 10 sequenced antibodies. DR GeneID; 281427; -. DR CTD; 5621; -. DR eggNOG; ENOG502S2A8; Eukaryota. DR HOGENOM; CLU_094631_0_0_1; -. DR InParanoid; P10279; -. DR OrthoDB; 5265139at2759; -. DR TreeFam; TF105188; -. DR EvolutionaryTrace; P10279; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0016234; C:inclusion body; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW. DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl. DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB. DR GO; GO:1903136; F:cuprous ion binding; IEA:Ensembl. DR GO; GO:0002151; F:G-quadruplex RNA binding; EXP:DisProt. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl. DR GO; GO:0140693; F:molecular condensate scaffold activity; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; IEA:Ensembl. DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; IEA:Ensembl. DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl. DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR DisProt; DP00783; -. DR Gene3D; 1.10.790.10; Prion/Doppel protein, beta-ribbon domain; 1. DR IDEAL; IID50068; -. DR InterPro; IPR000817; Prion. DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf. DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom. DR InterPro; IPR025860; Prion_N_dom. DR PANTHER; PTHR15506; DOPPEL PRION; 1. DR PANTHER; PTHR15506:SF2; MAJOR PRION PROTEIN; 1. DR Pfam; PF00377; Prion; 1. DR Pfam; PF11587; Prion_bPrPp; 1. DR PRINTS; PR00341; PRION. DR SMART; SM00157; PRP; 1. DR SUPFAM; SSF54098; Prion-like; 1. DR PROSITE; PS00291; PRION_1; 1. DR PROSITE; PS00706; PRION_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Amyloid; Cell membrane; Copper; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor; Lipoprotein; KW Membrane; Metal-binding; Prion; Reference proteome; Repeat; Signal; Zinc. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:2904126" FT CHAIN 25..241 FT /note="Major prion protein" FT /id="PRO_0000025627" FT PROPEP 242..264 FT /note="Removed in mature form" FT /evidence="ECO:0000255" FT /id="PRO_0000025628" FT REPEAT 54..62 FT /note="1" FT REPEAT 63..70 FT /note="2" FT REPEAT 71..78 FT /note="3" FT REPEAT 79..86 FT /note="4" FT REPEAT 87..94 FT /note="5" FT REPEAT 95..103 FT /note="6" FT REGION 25..241 FT /note="Interaction with GRB2, ERI3 and SYN1" FT /evidence="ECO:0000250|UniProtKB:P04925" FT REGION 25..41 FT /note="Interaction with ADGRG6" FT /evidence="ECO:0000250|UniProtKB:P04925" FT REGION 28..119 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 54..103 FT /note="6 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q" FT BINDING 72 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 73 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 74 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 80 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 81 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 82 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 88 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 89 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 90 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 96 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 98 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P04156" FT BINDING 99 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:P04156" FT LIPID 241 FT /note="GPI-anchor amidated alanine" FT /evidence="ECO:0000255" FT CARBOHYD 192 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT CARBOHYD 208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT DISULFID 190..225 FT VARIANT 60 FT /note="W -> R" FT /evidence="ECO:0000269|Ref.10" FT VARIANT 71..78 FT /note="Missing (in allele 2)" FT VARIANT 84..99 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:15477588" FT VARIANT 92..99 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:1362024, FT ECO:0000269|PubMed:15477588" FT VARIANT 94 FT /note="Q -> R" FT /evidence="ECO:0000269|Ref.10" FT VARIANT 98 FT /note="G -> GGWGQPHGG" FT /evidence="ECO:0000269|Ref.6" FT VARIANT 154 FT /note="S -> N" FT /evidence="ECO:0000269|PubMed:1362024, ECO:0000269|Ref.10" FT VARIANT 211 FT /note="E -> K" FT /evidence="ECO:0000269|PubMed:18625065" FT VARIANT 234 FT /note="Q -> R" FT /evidence="ECO:0000269|Ref.10" FT CONFLICT 106..108 FT /note="THG -> SHS (in Ref. 2; BAA01469)" FT /evidence="ECO:0000305" FT CONFLICT 218 FT /note="E -> K (in Ref. 2; BAA01467 and 4; BAA19253)" FT /evidence="ECO:0000305" FT TURN 3..8 FT /evidence="ECO:0007829|PDB:1SKH" FT HELIX 9..21 FT /evidence="ECO:0007829|PDB:1SKH" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:1SKH" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:2HH0" FT HELIX 136..138 FT /evidence="ECO:0007829|PDB:1DWY" FT STRAND 139..141 FT /evidence="ECO:0007829|PDB:1DWY" FT HELIX 155..164 FT /evidence="ECO:0007829|PDB:4YX2" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:4YX2" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:4YX2" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:4YX2" FT HELIX 183..204 FT /evidence="ECO:0007829|PDB:4YX2" FT HELIX 211..233 FT /evidence="ECO:0007829|PDB:4YX2" SQ SEQUENCE 264 AA; 28614 MW; D6D214038316A231 CRC64; MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GWGQPHGGGG WGQGGTHGQW NKPSKPKTNM KHVAGAAAAG AVVGGLGGYM LGSAMSRPLI HFGSDYEDRY YRENMHRYPN QVYYRPVDQY SNQNNFVHDC VNITVKEHTV TTTTKGENFT ETDIKMMERV VEQMCITQYQ RESQAYYQRG ASVILFSSPP VILLISFLIF LIVG //