PRIO_SHEEP
ID PRIO_SHEEP Reviewed; 256 AA.
AC P23907; Q5ECG0; Q6V638; Q6V654; Q712V9; Q712W2; Q712W3; Q7JGT4;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Major prion protein;
DE Short=PrP;
DE AltName: CD_antigen=CD230;
DE Flags: Precursor;
GN Name=PRNP; Synonyms=PRP, SIP;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RC STRAIN=Suffolk; TISSUE=Spleen;
RX PubMed=1969635; DOI=10.1073/pnas.87.7.2476;
RA Goldmann W., Hunter N., Foster J.D., Salbaum J.M., Beyreuther K., Hope J.;
RT "Two alleles of a neural protein gene linked to scrapie in sheep.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2476-2480(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RC STRAIN=Suffolk; TISSUE=Brain;
RX PubMed=7926780; DOI=10.1101/gad.8.8.959;
RA Westaway D., Zuliani V., Cooper C.M., da Costa M., Neuman S., Jenny A.L.,
RA Detwiler L., Prusiner S.B.;
RT "Homozygosity for prion protein alleles encoding glutamine-171 renders
RT sheep susceptible to natural scrapie.";
RL Genes Dev. 8:959-969(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RC TISSUE=Brain;
RX PubMed=9799790; DOI=10.1101/gr.8.10.1022;
RA Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., Acharya C.,
RA Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., Hood L.E.;
RT "Complete genomic sequence and analysis of the prion protein gene region
RT from three mammalian species.";
RL Genome Res. 8:1022-1037(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RX PubMed=10466827; DOI=10.1099/0022-1317-80-8-2275;
RA Goldmann W., O'Neill G., Cheung F., Charleson F., Ford P., Hunter N.;
RT "PrP (prion) gene expression in sheep may be modulated by alternative
RT polyadenylation of its messenger RNA.";
RL J. Gen. Virol. 80:2275-2283(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RX PubMed=14970684; DOI=10.1159/000075730;
RA Seabury C.M., Derr J.N.;
RT "Identification of a novel ovine PrP polymorphism and scrapie-resistant
RT genotypes for St. Croix White and a related composite breed.";
RL Cytogenet. Genome Res. 102:85-88(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-136; VAL-136; PHE-141;
RP HIS-154; GLN-171 AND LYS-171.
RX PubMed=14769911; DOI=10.1099/vir.0.19520-0;
RA Billinis C., Psychas V., Leontides L., Spyrou V., Argyroudis S.,
RA Vlemmas I., Leontides S., Sklaviadis T., Papadopoulos O.;
RT "Prion protein gene polymorphisms in healthy and scrapie affected sheep in
RT Greece.";
RL J. Gen. Virol. 85:547-554(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RA Inoue S., Watanabe A., Horiuchi M., Ishiguro N., Shinagawa M.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-136; PHE-141; GLN-171
RP AND GLN-211.
RA Bossers A.;
RT "PrP allelic variants associated with natural scrapie.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-136 AND GLN-171.
RA Heaton M.P., Leymaster K.A., Clawson M.L., Laegreid W.W.;
RT "A set of genotyping controls for 15 haplotype combinations of ovine PRNP
RT codons 136, 154, and 171.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP PROTEIN SEQUENCE OF 160-188 AND 198-207, GLYCOSYLATION AT ASN-184 AND
RP ASN-200, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=33600485; DOI=10.1371/journal.ppat.1009232;
RA Nakic N., Tran T.H., Novokmet M., Andreoletti O., Lauc G., Legname G.;
RT "Site-specific analysis of N-glycans from different sheep prion strains.";
RL PLoS Pathog. 17:e1009232-e1009232(2021).
RN [11]
RP IDENTIFICATION IN COMPLEX WITH CES5A; CLU; BPI; MANBA AND GLB1.
RC TISSUE=Epididymis;
RX PubMed=16029166; DOI=10.1042/bj20050459;
RA Ecroyd H., Belghazi M., Dacheux J.-L., Gatti J.-L.;
RT "The epididymal soluble prion protein forms a high-molecular-mass complex
RT in association with hydrophobic proteins.";
RL Biochem. J. 392:211-219(2005).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 128-233.
RX PubMed=15037077; DOI=10.1016/j.jmb.2003.12.059;
RA Haire L.F., Whyte S.M., Vasisht N., Gill A.C., Verma C., Dodson E.J.,
RA Dodson G.G., Bayley P.M.;
RT "The crystal structure of the globular domain of sheep prion protein.";
RL J. Mol. Biol. 336:1175-1183(2004).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 115-234 IN COMPLEX WITH ANTIBODY.
RX PubMed=15240887; DOI=10.1073/pnas.0400014101;
RA Eghiaian F., Grosclaude J., Lesceu S., Debey P., Doublet B., Treguer E.,
RA Rezaei H., Knossow M.;
RT "Insight into the PrPC-->PrPSc conversion from the structures of antibody-
RT bound ovine prion scrapie-susceptibility variants.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10254-10259(2004).
RN [14]
RP STRUCTURE BY NMR OF 124-234.
RX PubMed=15647367; DOI=10.1073/pnas.0408937102;
RA Lysek D.A., Schorn C., Nivon L.G., Esteve-Moya V., Christen B.,
RA Calzolai L., von Schroetter C., Fiorito F., Herrmann T., Guentert P.,
RA Wuethrich K.;
RT "Prion protein NMR structures of cats, dogs, pigs, and sheep.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:640-645(2005).
RN [15]
RP STRUCTURE BY NMR OF 167-234, 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 [16]
RP VARIANTS SCRAPIE VAL-136; HIS-154 AND GLN-171, AND POLYMORPHISM.
RX PubMed=1681027; DOI=10.1099/0022-1317-72-10-2411;
RA Goldmann W., Hunter N., Benson G., Foster J.D., Hope J.;
RT "Different scrapie-associated fibril proteins (PrP) are encoded by lines of
RT sheep selected for different alleles of the Sip gene.";
RL J. Gen. Virol. 72:2411-2417(1991).
RN [17]
RP VARIANTS SCRAPIE THR-112; VAL-136 AND HIS-154.
RX PubMed=8094373; DOI=10.1006/geno.1993.1006;
RA Laplanche J.-L., Chatelain J., Westaway D., Thomas S., Dussaucy M.,
RA Brugere-Picoux J., Launay J.-M.;
RT "PrP polymorphisms associated with natural scrapie discovered by denaturing
RT gradient gel electrophoresis.";
RL Genomics 15:30-37(1993).
RN [18]
RP VARIANTS SCRAPIE VAL-136 AND HIS-171, AND VARIANT HIS-154.
RX PubMed=7897344; DOI=10.1099/0022-1317-76-3-509;
RA Belt P.B.G.M., Muileman I.H., Schreuder B.E.C., Bos-De Ruijter J.,
RA Gielkens A.L.J., Smits M.A.;
RT "Identification of five allelic variants of the sheep PrP gene and their
RT association with natural scrapie.";
RL J. Gen. Virol. 76:509-517(1995).
RN [19]
RP VARIANTS THR-137; PHE-141 AND GLN-211.
RX PubMed=8887505; DOI=10.1099/0022-1317-77-10-2669;
RA Bossers A., Schreuder B.E.C., Muileman I.H., Belt P.B.G.M., Smits M.A.;
RT "PrP genotype contributes to determining survival times of sheep with
RT natural scrapie.";
RL J. Gen. Virol. 77:2669-2673(1996).
CC -!- FUNCTION: Its primary physiological function is unclear. Has
CC cytoprotective activity against internal or environmental stresses. May
CC play a role in neuronal development and synaptic plasticity. May be
CC required for neuronal myelin sheath maintenance. 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).
CC Association with GPC1 (via its heparan sulfate chains) targets PRNP to
CC lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated
CC GPC1 deaminase degradation of its heparan sulfate side chains (By
CC 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
CC SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this
CC interaction alters MGRN1 subcellular location and causes lysosomal
CC enlargement. Interacts with KIAA1191. {ECO:0000250|UniProtKB:P04156,
CC ECO:0000250|UniProtKB:P04925}.
CC -!- INTERACTION:
CC P23907; P23907: PRNP; NbExp=3; IntAct=EBI-7670302, EBI-7670302;
CC P23907; P04156: PRNP; Xeno; NbExp=3; IntAct=EBI-7670302, 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 -!- POLYMORPHISM: A number of amino acid polymorphism sites that influence
CC scrapie susceptibility and transmission have been described. These are
CC alanine to threonine or valine at codon 136, arginine to histidine at
CC codon 154, and arginine to glutamine, histidine or lysine at codon 171.
CC A number of allelic variants have been described based on the amino
CC acids found at these three positions: VRQ, ARQ, AHQ, TRQ, ARK, ARR and
CC ARH. {ECO:0000269|PubMed:14769911}.
CC -!- DISEASE: Note=Found in high quantity in the brain of humans and animals
CC infected with degenerative neurological diseases such as kuru,
CC Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS),
CC scrapie, bovine spongiform encephalopathy (BSE), transmissible mink
CC encephalopathy (TME), etc. {ECO:0000305}.
CC -!- DISEASE: Note=Scrapie is a transmissible neurodegenerative disorder of
CC sheep and goats. Most sheep that contract the disease naturally die
CC between 24 and 50 months of age. The incubation period in sheep depends
CC on the strain(s) of the infecting pathogen, sheep age at exposure, and
CC the sheep genotype. Scrapie can be spread between flockmates, or it can
CC be transmitted from an infected ewe to its lamb.
CC {ECO:0000269|PubMed:1681027, ECO:0000269|PubMed:7897344,
CC ECO:0000269|PubMed:8094373}.
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 F7VJQ3) 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}.
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DR EMBL; M31313; AAB97765.1; -; Genomic_DNA.
DR EMBL; X79912; CAA56283.1; -; Genomic_DNA.
DR EMBL; U67922; AAC78726.1; -; Genomic_DNA.
DR EMBL; AJ223072; CAA11073.1; -; Genomic_DNA.
DR EMBL; AY350241; AAR14214.1; -; Genomic_DNA.
DR EMBL; AY350242; AAR14215.1; -; Genomic_DNA.
DR EMBL; AY350243; AAR14216.1; -; Genomic_DNA.
DR EMBL; AY350245; AAR14218.1; -; Genomic_DNA.
DR EMBL; AY350246; AAR14219.1; -; Genomic_DNA.
DR EMBL; AY350248; AAR14221.1; -; Genomic_DNA.
DR EMBL; AY350249; AAR14222.1; -; Genomic_DNA.
DR EMBL; AY350250; AAR14223.1; -; Genomic_DNA.
DR EMBL; AY350254; AAR14227.1; -; Genomic_DNA.
DR EMBL; AY350256; AAR14229.1; -; Genomic_DNA.
DR EMBL; AY350257; AAR14230.1; -; Genomic_DNA.
DR EMBL; AY350261; AAR14234.1; -; Genomic_DNA.
DR EMBL; AY350264; AAR14237.1; -; Genomic_DNA.
DR EMBL; AY350267; AAR14240.1; -; Genomic_DNA.
DR EMBL; AY350268; AAR14241.1; -; Genomic_DNA.
DR EMBL; AY350271; AAR14244.1; -; Genomic_DNA.
DR EMBL; AY350272; AAR14245.1; -; Genomic_DNA.
DR EMBL; AY350273; AAR14246.1; -; Genomic_DNA.
DR EMBL; AY350275; AAR14248.1; -; Genomic_DNA.
DR EMBL; AJ567984; CAE00186.1; -; Genomic_DNA.
DR EMBL; AJ567985; CAE00187.1; -; Genomic_DNA.
DR EMBL; AJ567986; CAE00188.2; -; Genomic_DNA.
DR EMBL; AJ567988; CAE00190.1; -; Genomic_DNA.
DR EMBL; D38179; BAA07376.1; -; Genomic_DNA.
DR EMBL; AJ000680; CAA04235.1; -; Genomic_DNA.
DR EMBL; AJ000681; CAA04236.1; -; Genomic_DNA.
DR EMBL; AJ000736; CAA04274.1; -; Genomic_DNA.
DR EMBL; AJ000738; CAA04276.1; -; Genomic_DNA.
DR EMBL; AJ000739; CAA04277.1; -; Genomic_DNA.
DR EMBL; AY907685; AAW88332.1; -; Genomic_DNA.
DR EMBL; AY907689; AAW88336.1; -; Genomic_DNA.
DR EMBL; AY907690; AAW88337.1; -; Genomic_DNA.
DR EMBL; AY907691; AAW88338.1; -; Genomic_DNA.
DR RefSeq; NP_001009481.1; NM_001009481.1.
DR RefSeq; XP_012043480.1; XM_012188090.2.
DR PDB; 1G04; NMR; -; A=145-169.
DR PDB; 1M25; NMR; -; A=145-169.
DR PDB; 1S4T; NMR; -; A=138-158.
DR PDB; 1TPX; X-ray; 2.56 A; A=114-234.
DR PDB; 1TQB; X-ray; 2.55 A; A=127-228.
DR PDB; 1TQC; X-ray; 2.80 A; A=127-228.
DR PDB; 1UW3; X-ray; 2.04 A; A=128-233.
DR PDB; 1XYU; NMR; -; A=124-234.
DR PDB; 1Y2S; NMR; -; A=124-234.
DR PDB; 2KTM; NMR; -; A=172-234.
DR PDB; 2MV8; NMR; -; A=103-234.
DR PDB; 2MV9; NMR; -; A=103-234.
DR PDB; 2N53; NMR; -; A=103-234.
DR PDB; 2RMV; NMR; -; A=145-169.
DR PDB; 2RMW; NMR; -; A=145-169.
DR PDBsum; 1G04; -.
DR PDBsum; 1M25; -.
DR PDBsum; 1S4T; -.
DR PDBsum; 1TPX; -.
DR PDBsum; 1TQB; -.
DR PDBsum; 1TQC; -.
DR PDBsum; 1UW3; -.
DR PDBsum; 1XYU; -.
DR PDBsum; 1Y2S; -.
DR PDBsum; 2KTM; -.
DR PDBsum; 2MV8; -.
DR PDBsum; 2MV9; -.
DR PDBsum; 2N53; -.
DR PDBsum; 2RMV; -.
DR PDBsum; 2RMW; -.
DR AlphaFoldDB; P23907; -.
DR BMRB; P23907; -.
DR SASBDB; P23907; -.
DR SMR; P23907; -.
DR DIP; DIP-60917N; -.
DR IntAct; P23907; 1.
DR MINT; P23907; -.
DR STRING; 9940.ENSOARP00000004991; -.
DR BindingDB; P23907; -.
DR ChEMBL; CHEMBL2406893; -.
DR TCDB; 1.C.48.1.1; the prion peptide (prp) family.
DR GlyConnect; 2954; 70 N-Linked glycans (2 sites).
DR GlyConnect; 2955; 70 N-Linked glycans (2 sites).
DR ABCD; P23907; 1 sequenced antibody.
DR Ensembl; ENSOART00000005076; ENSOARP00000004991; ENSOARG00000004668.
DR Ensembl; ENSOART00020017839; ENSOARP00020014736; ENSOARG00020011739.
DR GeneID; 493887; -.
DR KEGG; oas:493887; -.
DR CTD; 5621; -.
DR eggNOG; ENOG502S2A8; Eukaryota.
DR HOGENOM; CLU_094631_0_0_1; -.
DR OMA; HNPGYPH; -.
DR EvolutionaryTrace; P23907; -.
DR PRO; PR:P23907; -.
DR Proteomes; UP000002356; Chromosome 13.
DR Bgee; ENSOARG00000004668; Expressed in cerebellum and 52 other tissues.
DR ExpressionAtlas; P23907; baseline.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
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: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:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008017; F:microtubule binding; ISS:AgBase.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0015631; F:tubulin binding; ISS:AgBase.
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:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1902938; P:regulation of intracellular calcium activated chloride channel activity; IEA:Ensembl.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR000817; Prion.
DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR InterPro; IPR025860; Prion_N_dom.
DR Pfam; PF00377; Prion; 1.
DR Pfam; PF11587; Prion_bPrPp; 1.
DR PRINTS; PR00341; PRION.
DR SMART; SM00157; PRP; 1.
DR SUPFAM; SSF54098; SSF54098; 1.
DR PROSITE; PS00291; PRION_1; 1.
DR PROSITE; PS00706; PRION_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Cell membrane; Copper; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor;
KW Lipoprotein; Membrane; Metal-binding; Prion; Reference proteome; Repeat;
KW Signal; Zinc.
FT SIGNAL 1..24
FT CHAIN 25..233
FT /note="Major prion protein"
FT /id="PRO_0000025727"
FT PROPEP 234..256
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025728"
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..95
FT /note="5"
FT REGION 25..233
FT /note="Interaction with GRB2, ERI3 and SYN1"
FT /evidence="ECO:0000250|UniProtKB:P04925"
FT REGION 28..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 54..95
FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q"
FT BINDING 64
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 65
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 66
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 72
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 73
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 74
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 80
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 81
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 82
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 88
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 90
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT BINDING 91
FT /ligand="Cu(2+)"
FT /ligand_id="ChEBI:CHEBI:29036"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:P04156"
FT LIPID 233
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:33600485"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:33600485"
FT DISULFID 182..217
FT VARIANT 112
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:8094373"
FT VARIANT 136
FT /note="A -> T"
FT /evidence="ECO:0000269|PubMed:14769911"
FT VARIANT 136
FT /note="A -> V (in scrapie; short incubation; sA allele)"
FT /evidence="ECO:0000269|PubMed:14769911,
FT ECO:0000269|PubMed:1681027, ECO:0000269|PubMed:7897344,
FT ECO:0000269|PubMed:8094373, ECO:0000269|Ref.8,
FT ECO:0000269|Ref.9"
FT VARIANT 137
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:8887505"
FT VARIANT 141
FT /note="L -> F"
FT /evidence="ECO:0000269|PubMed:14769911,
FT ECO:0000269|PubMed:8887505, ECO:0000269|Ref.8"
FT VARIANT 154
FT /note="R -> H"
FT /evidence="ECO:0000269|PubMed:14769911,
FT ECO:0000269|PubMed:1681027, ECO:0000269|PubMed:7897344,
FT ECO:0000269|PubMed:8094373"
FT VARIANT 171
FT /note="R -> H (in scrapie; low incidence)"
FT /evidence="ECO:0000269|PubMed:7897344"
FT VARIANT 171
FT /note="R -> K"
FT /evidence="ECO:0000269|PubMed:14769911"
FT VARIANT 171
FT /note="R -> Q (linked to susceptibility to scrapie)"
FT /evidence="ECO:0000269|PubMed:10466827,
FT ECO:0000269|PubMed:14769911, ECO:0000269|PubMed:14970684,
FT ECO:0000269|PubMed:1681027, ECO:0000269|PubMed:1969635,
FT ECO:0000269|PubMed:7926780, ECO:0000269|PubMed:9799790,
FT ECO:0000269|Ref.8, ECO:0000269|Ref.9"
FT VARIANT 211
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:8887505, ECO:0000269|Ref.8,
FT ECO:0000269|Ref.9"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:2N53"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:2N53"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1XYU"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1Y2S"
FT TURN 144..146
FT /evidence="ECO:0007829|PDB:1S4T"
FT HELIX 147..155
FT /evidence="ECO:0007829|PDB:1UW3"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:1UW3"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:1G04"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:1UW3"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:1UW3"
FT HELIX 176..196
FT /evidence="ECO:0007829|PDB:1UW3"
FT HELIX 203..229
FT /evidence="ECO:0007829|PDB:1UW3"
SQ SEQUENCE 256 AA; 27915 MW; 7FFBEA6C6FDBF8BB CRC64;
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW
GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS QWNKPSKPKT NMKHVAGAAA
AGAVVGGLGG YMLGSAMSRP LIHFGNDYED RYYRENMYRY PNQVYYRPVD RYSNQNNFVH
DCVNITVKQH TVTTTTKGEN FTETDIKIME RVVEQMCITQ YQRESQAYYQ RGASVILFSS
PPVILLISFL IFLIVG
