ID PRIO_SHEEP Reviewed; 256 AA.
AC P23907; Q5ECG0; Q6V638; Q6V654; Q712W2; Q712W3; Q7JGT4;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-APR-2013, entry version 103.
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;
OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC Pecora; Bovidae; 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.,
RA 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;
RA Westaway D., Zuliani V., Cooper C.M., da Costa M., Neuman S.,
RA Jenny A.L., 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;
RA Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L.,
RA Acharya C., Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B.,
RA Hood L.E.;
RT "Complete genomic sequence and analysis of the prion protein gene
RT region from three mammalian species.";
RL Genome Res. 8:1022-1037(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-171.
RX PubMed=10466827;
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-
RT resistant genotypes for St. Croix White and a related composite
RT breed.";
RL Cytogenet. Genome Res. 102:85-88(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-141 AND GLN-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
RT sheep in 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 PHE-141; GLN-171 AND
RP 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 VARIANT 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
RT PRNP codons 136, 154, and 171.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
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
RT complex in association with hydrophobic proteins.";
RL Biochem. J. 392:211-219(2005).
RN [11]
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
RT protein.";
RL J. Mol. Biol. 336:1175-1183(2004).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 115-234 IN COMPLEX WITH
RP ANTIBODY.
RX PubMed=15240887; DOI=10.1073/pnas.0400014101;
RA Eghiaian F., Grosclaude J., Lesceu S., Debey P., Doublet B.,
RA Treguer E., Rezaei H., Knossow M.;
RT "Insight into the PrPC-->PrPSc conversion from the structures of
RT antibody-bound ovine prion scrapie-susceptibility variants.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10254-10259(2004).
RN [13]
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 [14]
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 [15]
RP VARIANTS SCRAPIE VAL-136; HIS-154 AND GLN-171.
RX PubMed=1681027;
RA Goldmann W., Hunter N., Benson G., Foster J.D., Hope J.;
RT "Different scrapie-associated fibril proteins (PrP) are encoded by
RT lines of sheep selected for different alleles of the Sip gene.";
RL J. Gen. Virol. 72:2411-2417(1991).
RN [16]
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
RT denaturing gradient gel electrophoresis.";
RL Genomics 15:30-37(1993).
RN [17]
RP VARIANTS SCRAPIE VAL-136 AND HIS-171, AND VARIANT HIS-154.
RX PubMed=7897344;
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
RT their association with natural scrapie.";
RL J. Gen. Virol. 76:509-517(1995).
RN [18]
RP VARIANTS THR-137; PHE-141 AND GLN-211.
RX PubMed=8887505;
RA Bossers A., Schreuder B.E.C., Muileman I.H., Belt P.B.G.M.,
RA 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: May play a role in neuronal development and synaptic
CC plasticity. May be required for neuronal myelin sheath
CC maintenance. May play a role in iron uptake and iron homeostasis.
CC Soluble oligomers are toxic to cultured neuroblastoma cells and
CC induce apoptosis (in vitro). Association with GPC1 (via its
CC heparan sulfate chains) targets PRNP to lipid rafts. Also provides
CC Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase
CC degradation of its heparan sulfate side chains (By similarity).
CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into
CC amyloid fibrils containing a cross-beta spine, formed by a steric
CC zipper of superposed beta-strands. Soluble oligomers may represent
CC an intermediate stage on the path to fibril formation. Copper
CC binding may promote oligomerization. Interacts with APP, GRB2,
CC ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP
CC interacts with MGRN1; this interaction alters MGRN1 subcellular
CC location and causes lysosomal enlargement (By similarity).
CC Interacts with KIAA1191 (By similarity).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor (By
CC similarity). Golgi apparatus (By similarity). Note=Targeted to
CC lipid rafts via association with the heparan sulfate chains of
CC GPC1. Colocates, in the presence of CU(2+), to vesicles in para-
CC and perinuclear regions, where both proteins undergo
CC internalization. Heparin displaces PRNP from lipid rafts and
CC promotes endocytosis (By similarity).
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
CC trigger oligomerization (By similarity).
CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats.
CC At low copper concentrations, the sidechains of His residues from
CC three or four repeats contribute to the binding of a single copper
CC ion. Alternatively, a copper ion can be bound by interaction with
CC the sidechain and backbone amide nitrogen of a single His residue.
CC The observed copper binding stoichiometry suggests that two repeat
CC regions cooperate to stabilize the binding of a single copper ion.
CC At higher copper concentrations, each octamer can bind one copper
CC ion by interactions with the His sidechain and Gly backbone atoms.
CC A mixture of binding types may occur, especially in the case of
CC octamer repeat expansion. Copper binding may stabilize the
CC conformation of this region and may promote oligomerization (By
CC similarity).
CC -!- DISEASE: Note=Polymorphism at position 171 may be related to the
CC alleles of scrapie incubation-control (SIC) gene in this species.
CC -!- DISEASE: Note=Found in high quantity in the brain of humans and
CC animals infected with degenerative neurological diseases such as
CC kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler
CC syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE),
CC transmissible mink encephalopathy (TME), etc.
CC -!- DISEASE: Note=Scrapie is a transmissible neurodegenerative
CC disorder of sheep and goats. Most sheep that contract the disease
CC naturally die between 24 and 50 months of age. The incubation
CC period in sheep depends on the strain(s) of the infecting
CC pathogen, sheep age at exposure, and the sheep genotype. The
CC survival time is mainly determined by a single genetic locus, SIP,
CC which has two alleles, susceptible (sa) and resistant (pa). Short
CC incubation period is conferred by the partially dominant sa
CC allele. Scrapie can be spread between flockmates, or it can be
CC transmitted from an infected ewe to its lamb.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene
CC which also produces the major prion protein/PRNP from an
CC overlapping reading frame.
CC -!- MISCELLANEOUS: The alternative prion protein/AltPrP (AC F7VJQ3)
CC and PRNP have no apparent direct functional relation since a
CC mutation that removes the start codon of the AltPrP has no
CC apparent effect on the biology of PRNP (By similarity). In mouse
CC and hamster, the alternative initiation AUG codon is absent and is
CC replaced by a GUG codon.
CC -!- SIMILARITY: Belongs to the prion family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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; 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; AJ000739; CAA04277.1; -; 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 UniGene; Oar.765; -.
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=167-234.
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 ProteinModelPortal; P23907; -.
DR SMR; P23907; 1-30, 127-228.
DR TCDB; 1.C.48.1.1; prion peptide fragment (PrP-F) family.
DR GeneID; 493887; -.
DR CTD; 5621; -.
DR HOVERGEN; HBG008260; -.
DR EvolutionaryTrace; P23907; -.
DR GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:AgBase.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR Gene3D; 1.10.790.10; -; 1.
DR InterPro; IPR000817; Prion.
DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom.
DR InterPro; IPR025860; Prion_N_dom.
DR PANTHER; PTHR11522; PTHR11522; 1.
DR Pfam; PF00377; Prion; 1.
DR Pfam; PF11587; Prion_bPrPp; 1.
DR PRINTS; PR00341; PRION.
DR SMART; SM00157; PRP; 1.
DR SUPFAM; SSF54098; Prion; 1.
DR PROSITE; PS00291; PRION_1; 1.
DR PROSITE; PS00706; PRION_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amyloid; Cell membrane; Copper; Disease mutation;
KW Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor;
KW Lipoprotein; Membrane; Metal-binding; Polymorphism; Prion; Repeat;
KW Signal; Zinc.
FT SIGNAL 1 24
FT CHAIN 25 233 Major prion protein.
FT /FTId=PRO_0000025727.
FT PROPEP 234 256 Removed in mature form (Potential).
FT /FTId=PRO_0000025728.
FT REPEAT 54 62 1.
FT REPEAT 63 70 2.
FT REPEAT 71 78 3.
FT REPEAT 79 86 4.
FT REPEAT 87 95 5.
FT REGION 25 233 Interaction with GRB2, ERI3 and SYN1 (By
FT similarity).
FT REGION 54 95 5 X 8 AA tandem repeats of P-H-G-G-G-W-G-
FT Q.
FT METAL 64 64 Copper or zinc 1 (By similarity).
FT METAL 65 65 Copper or zinc 1; via amide nitrogen (By
FT similarity).
FT METAL 66 66 Copper or zinc 1; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT METAL 72 72 Copper or zinc 2 (By similarity).
FT METAL 73 73 Copper or zinc 2; via amide nitrogen (By
FT similarity).
FT METAL 74 74 Copper or zinc 2; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT METAL 80 80 Copper or zinc 3 (By similarity).
FT METAL 81 81 Copper or zinc 3; via amide nitrogen (By
FT similarity).
FT METAL 82 82 Copper or zinc 3; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT METAL 88 88 Copper or zinc 4 (By similarity).
FT METAL 89 89 Copper or zinc 4; via amide nitrogen (By
FT similarity).
FT METAL 90 90 Copper or zinc 4; via amide nitrogen and
FT carbonyl oxygen (By similarity).
FT LIPID 233 233 GPI-anchor amidated alanine (Potential).
FT CARBOHYD 184 184 N-linked (GlcNAc...) (Probable).
FT CARBOHYD 200 200 N-linked (GlcNAc...) (Probable).
FT DISULFID 182 217
FT VARIANT 112 112 M -> T.
FT VARIANT 136 136 A -> V (in scrapie; short incubation; sA
FT allele).
FT VARIANT 137 137 M -> T.
FT VARIANT 141 141 L -> F.
FT VARIANT 154 154 R -> H.
FT VARIANT 171 171 R -> H (in scrapie; low incidence).
FT VARIANT 171 171 R -> Q (linked to susceptibility to
FT scrapie).
FT VARIANT 211 211 R -> Q.
FT STRAND 128 130
FT STRAND 131 133
FT TURN 144 146
FT HELIX 147 155
FT HELIX 157 159
FT STRAND 165 167
FT HELIX 169 171
FT STRAND 173 175
FT HELIX 176 196
FT HELIX 203 229
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
//
