Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P04925 (PRIO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Major prion protein

Short name=PrP
Alternative name(s):
PrP27-30
PrP33-35C
CD_antigen=CD230
Gene names
Name:Prnp
Synonyms:Prn-p, Prp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length254 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) By similarity. Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu2+ or ZN2+ for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains. Ref.12 Ref.14 Ref.17 Ref.18

Subunit structure

Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on the path to fibril formation. Copper binding may promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement By similarity. Interacts with APP. Interacts with KIAA1191 By similarity. Ref.11 Ref.15 Ref.17

Subcellular location

Cell membrane; Lipid-anchorGPI-anchor By similarity. Golgi apparatus By similarity. Note: Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of CU2+, to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis. Ref.9 Ref.11 Ref.12 Ref.13

Tissue specificity

Highly expressed in the brain, lung, kidney and heart. Expressed at low levels in the liver and spleen. Ref.14 Ref.18

Domain

The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization By similarity.

Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization By similarity.

Post-translational modification

N-glycosylated. Ref.14 Ref.18

Involvement in disease

Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.

Disruption phenotype

No obvious phenotype. Mice develop chronic demyelinating polyneuropathy after 60 weeks. Mice show abnormally low iron levels throughout the body, and are mildly anemic. Iron accumulates in duodenum enterocytes, suggesting impaired transport from the intestine to the blood. Ref.7 Ref.8 Ref.14 Ref.17 Ref.18 Ref.20

Sequence similarities

Belongs to the prion family.

Ontologies

Keywords
   Cellular componentAmyloid
Cell membrane
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
   LigandCopper
Metal-binding
Zinc
   Molecular functionPrion
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Hydroxylation
Lipoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular copper ion homeostasis

Traceable author statement PubMed 11756421. Source: MGI

learning or memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell receptor signaling pathway

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of activated T cell proliferation

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 15753097. Source: MGI

negative regulation of calcineurin-NFAT signaling cascade

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of interferon-gamma production

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of interleukin-17 production

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of interleukin-2 production

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 20145049. Source: BHF-UCL

nucleobase-containing compound metabolic process

Traceable author statement PubMed 12206674. Source: MGI

protein homooligomerization

Inferred from electronic annotation. Source: InterPro

regulation of potassium ion transmembrane transport

Inferred from genetic interaction PubMed 24225951. Source: MGI

regulation of protein localization

Inferred from mutant phenotype PubMed 10037495. Source: MGI

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to copper ion

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from direct assay PubMed 12500977. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 11756421. Source: MGI

anchored component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

endoplasmic reticulum

Inferred from direct assay PubMed 11756421. Source: MGI

membrane

Inferred from direct assay PubMed 24225951. Source: MGI

membrane raft

Inferred from direct assay PubMed 10037495PubMed 12927782. Source: MGI

nucleolus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functioncopper ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 20345906PubMed 22449963PubMed 23892077. Source: IntAct

protein binding

Inferred from physical interaction PubMed 15301538PubMed 22285492. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself9EBI-768613,EBI-768613
Grb2Q606317EBI-768613,EBI-1688
PRNPP041563EBI-768613,EBI-977302From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222
Chain23 – 230208Major prion protein
PRO_0000025697
Propeptide231 – 25424Removed in mature form By similarity
PRO_0000025698

Regions

Repeat51 – 5881
Repeat59 – 6682
Repeat67 – 7483
Repeat75 – 8284
Repeat83 – 9085
Region23 – 231209Interaction with GRB2, ERI3 and SYN1
Region51 – 90405 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q

Sites

Metal binding601Copper or zinc 1 By similarity
Metal binding611Copper or zinc 1; via amide nitrogen By similarity
Metal binding621Copper or zinc 1; via amide nitrogen and carbonyl oxygen By similarity
Metal binding681Copper or zinc 2 By similarity
Metal binding691Copper or zinc 2; via amide nitrogen By similarity
Metal binding701Copper or zinc 2; via amide nitrogen and carbonyl oxygen By similarity
Metal binding761Copper or zinc 3 By similarity
Metal binding771Copper or zinc 3; via amide nitrogen By similarity
Metal binding781Copper or zinc 3; via amide nitrogen and carbonyl oxygen By similarity
Metal binding841Copper or zinc 4 By similarity
Metal binding851Copper or zinc 4; via amide nitrogen By similarity
Metal binding861Copper or zinc 4; via amide nitrogen and carbonyl oxygen By similarity

Amino acid modifications

Modified residue441Hydroxyproline
Lipidation2301GPI-anchor amidated serine By similarity
Glycosylation1801N-linked (GlcNAc...) Probable
Glycosylation1961N-linked (GlcNAc...) Ref.16
Disulfide bond178 ↔ 213

Natural variations

Natural variant1081L → F Linked to long incubation time.
Natural variant1891T → V Linked to long incubation time.

Experimental info

Mutagenesis1011P → L: No effect on interaction with GRB2. Ref.11
Mutagenesis1041P → L: No effect on interaction with GRB2. Ref.11
Sequence conflict1331M → V in AAA39996. Ref.2
Sequence conflict1331M → V in AAA39999. Ref.6

Secondary structure

.................. 254
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04925 [UniParc].

Last modified January 1, 1990. Version 2.
Checksum: D5331E6321826CC0

FASTA25427,977
        10         20         30         40         50         60 
MANLGYWLLA LFVTMWTDVG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGTWGQPH 

        70         80         90        100        110        120 
GGGWGQPHGG SWGQPHGGSW GQPHGGGWGQ GGGTHNQWNK PSKPKTNLKH VAGAAAAGAV 

       130        140        150        160        170        180 
VGGLGGYMLG SAMSRPMIHF GNDWEDRYYR ENMYRYPNQV YYRPVDQYSN QNNFVHDCVN 

       190        200        210        220        230        240 
ITIKQHTVTT TTKGENFTET DVKMMERVVE QMCVTQYQKE SQAYYDGRRS SSTVLFSSPP 

       250 
VILLISFLIF LIVG 

« Hide

References

« Hide 'large scale' references
[1]"Distinct prion proteins in short and long scrapie incubation period mice."
Westaway D., Goodman P.A., Mirenda C.A., McKinley M.P., Carlson G.A., Prusiner S.B.
Cell 51:651-662(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: I/LnJ and NZW.
[2]"Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent."
Locht C., Chesebro B., Race R., Keith J.M.
Proc. Natl. Acad. Sci. U.S.A. 83:6372-6376(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie."
Hope J., Multhaup G., Reekie L.J.D., Kimberlin R.H., Beyreuther K.
Eur. J. Biochem. 172:271-277(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE.
[4]"Complete genomic sequence and analysis of the prion protein gene region from three mammalian species."
Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., Acharya C., Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., Hood L.E.
Genome Res. 8:1022-1037(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: NZW.
Tissue: Brain.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain."
Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D., Bergstrom S., Robbins K., Mayer L., Keith J.M., Garon C., Haase A.
Nature 315:331-333(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-164.
[7]"Prion protein is necessary for normal synaptic function."
Collinge J., Whittington M.A., Sidle K.C., Smith C.J., Palmer M.S., Clarke A.R., Jefferys J.G.
Nature 370:295-297(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[8]"Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus."
Lledo P.M., Tremblay P., DeArmond S.J., Prusiner S.B., Nicoll R.A.
Proc. Natl. Acad. Sci. U.S.A. 93:2403-2407(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[9]"Copper stimulates endocytosis of the prion protein."
Pauly P.C., Harris D.A.
J. Biol. Chem. 273:33107-33110(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo."
Gill A.C., Ritchie M.A., Hunt L.G., Steane S.E., Davies K.G., Bocking S.P., Rhie A.G.O., Bennett A.D., Hope J.
EMBO J. 19:5324-5331(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: HYDROXYLATION AT PRO-44.
[11]"PrPC directly interacts with proteins involved in signaling pathways."
Spielhaupter C., Schaetzl H.M.
J. Biol. Chem. 276:44604-44612(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH GRB2; ERI3 AND SYN1, MUTAGENESIS OF PRO-101 AND PRO-104.
[12]"Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate."
Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.
J. Biol. Chem. 278:38956-38965(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: COPPER BINDING, SUBCELLULAR LOCATION, FUNCTION.
[13]"Copper-dependent co-internalization of the prion protein and glypican-1."
Cheng F., Lindqvist J., Haigh C.L., Brown D.R., Mani K.
J. Neurochem. 98:1445-1457(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, COPPER-BINDING.
[14]"Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis."
Steele A.D., Emsley J.G., Ozdinler P.H., Lindquist S., Macklis J.D.
Proc. Natl. Acad. Sci. U.S.A. 103:3416-3421(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, GLYCOSYLATION, FUNCTION, TISSUE SPECIFICITY.
[15]"Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegeneration."
Chakrabarti O., Hegde R.S.
Cell 137:1136-1147(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MGRN1.
[16]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-196.
[17]"Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers."
Lauren J., Gimbel D.A., Nygaard H.B., Gilbert J.W., Strittmatter S.M.
Nature 457:1128-1132(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH APP, FUNCTION.
[18]"Prion protein (PrP) knock-out mice show altered iron metabolism: a functional role for PrP in iron uptake and transport."
Singh A., Kong Q., Luo X., Petersen R.B., Meyerson H., Singh N.
PLoS ONE 4:E6115-E6115(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, GLYCOSYLATION, TISSUE SPECIFICITY.
[19]"Early onset prion disease from octarepeat expansion correlates with copper or zinc binding properties."
Stevens D.J., Walter E.D., Rodriguez A., Draper D., Davies P., Brown D.R., Millhauser G.L.
PLoS Pathog. 5:E1000390-E1000390(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: COPPER-BINDING.
[20]"Axonal prion protein is required for peripheral myelin maintenance."
Bremer J., Baumann F., Tiberi C., Wessig C., Fischer H., Schwarz P., Steele A.D., Toyka K.V., Nave K.A., Weis J., Aguzzi A.
Nat. Neurosci. 13:310-318(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[21]"NMR structure of the mouse prion protein domain PrP(121-321)."
Riek R., Hornemann S., Wider G., Bileter M., Glockshuber R., Wuethrich K.
Nature 382:180-182(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 120-230.
[22]"NMR characterization of the full-length recombinant murine prion protein, mPrP(23-231)."
Riek R., Hornemann S., Wider G., Glockshuber R., Wuethrich K.
FEBS Lett. 413:282-288(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 23-231.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M18070 Genomic DNA. Translation: AAA39997.1.
M18071 Genomic DNA. Translation: AAA39998.1.
M13685 mRNA. Translation: AAA39996.1.
U29186 Genomic DNA. Translation: AAC02804.1.
BC006703 mRNA. Translation: AAH06703.1.
M30384 mRNA. Translation: AAA39999.1.
CCDSCCDS16766.1.
PIRA23544. A29669.
RefSeqNP_001265185.1. NM_001278256.1.
NP_035300.1. NM_011170.3.
UniGeneMm.648.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AG2NMR-A123-225[»]
1XYXNMR-A120-231[»]
1Y15NMR-A120-231[»]
1Y16NMR-A120-231[»]
2K5ONMR-A120-231[»]
2KFMNMR-A120-231[»]
2KFONMR-A120-231[»]
2KU5NMR-A120-231[»]
2KU6NMR-A120-231[»]
2L1DNMR-A120-231[»]
2L1ENMR-A120-231[»]
2L1HNMR-A120-231[»]
2L1KNMR-A120-231[»]
2L39NMR-A118-231[»]
2L40NMR-A120-231[»]
3NVGX-ray1.48A137-142[»]
3NVHX-ray1.61A137-143[»]
4H88X-ray1.90A120-230[»]
4J8RX-ray2.30I/J67-82[»]
4MA7X-ray1.97A116-229[»]
4MA8X-ray2.20C116-229[»]
DisProtDP00265.
ProteinModelPortalP04925.
SMRP04925. Positions 2-28, 89-232.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202389. 38 interactions.
DIPDIP-4N.
IntActP04925. 11 interactions.
MINTMINT-214988.

Chemistry

BindingDBP04925.
ChEMBLCHEMBL3698.

PTM databases

PhosphoSiteP04925.

Proteomic databases

MaxQBP04925.
PaxDbP04925.
PRIDEP04925.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000091288; ENSMUSP00000088833; ENSMUSG00000079037.
GeneID19122.
KEGGmmu:19122.
UCSCuc008mly.2. mouse.

Organism-specific databases

CTD5621.
MGIMGI:97769. Prnp.

Phylogenomic databases

eggNOGNOG41716.
HOGENOMHOG000232077.
HOVERGENHBG008260.
InParanoidP04925.
KOK05634.
OMAHNPGYPH.
OrthoDBEOG7DRJ4Q.
PhylomeDBP04925.
TreeFamTF105188.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.

Gene expression databases

ArrayExpressP04925.
BgeeP04925.
CleanExMM_PRNP.
GenevestigatorP04925.

Family and domain databases

Gene3D1.10.790.10. 1 hit.
InterProIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
IPR025860. Prion_N_dom.
[Graphical view]
PANTHERPTHR11522. PTHR11522. 1 hit.
PfamPF00377. Prion. 1 hit.
PF11587. Prion_bPrPp. 1 hit.
[Graphical view]
PRINTSPR00341. PRION.
SMARTSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMSSF54098. SSF54098. 1 hit.
PROSITEPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRNP. mouse.
EvolutionaryTraceP04925.
NextBio295714.
PMAP-CutDBP04925.
PROP04925.
SOURCESearch...

Entry information

Entry namePRIO_MOUSE
AccessionPrimary (citable) accession number: P04925
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 1, 1990
Last modified: July 9, 2014
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot