P04925 (PRIO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	254 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The function of PrP is still under debate. 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). Ref.12 Ref.15 Ref.16
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. Ref.11 Ref.13 Ref.15
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Golgi apparatus Ref.9 Ref.11.
Tissue specificity	Highly expressed in the brain, lung, kidney and heart. Expressed at low levels in the liver and spleen. Ref.12 Ref.16
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.12 Ref.14 Ref.16
Involvement in disease	Note=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.12 Ref.15 Ref.16 Ref.18
Sequence similarities	Belongs to the prion family.

Ontologies

Keywords
Cellular component	Amyloid Cell membrane Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Copper Metal-binding Zinc
Molecular function	Prion
PTM	Disulfide bond GPI-anchor Glycoprotein Hydroxylation Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cellular copper ion homeostasis Traceable author statement. Source: MGI negative regulation of T cell receptor signaling pathway Inferred from mutant phenotype. Source: BHF-UCL negative regulation of activated T cell proliferation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of calcineurin-NFAT signaling pathway Inferred from mutant phenotype. Source: BHF-UCL negative regulation of interferon-gamma production Inferred from mutant phenotype. Source: BHF-UCL negative regulation of interleukin-17 production Inferred from mutant phenotype. Source: BHF-UCL negative regulation of interleukin-2 production Inferred from mutant phenotype. Source: BHF-UCL negative regulation of protein phosphorylation Inferred from mutant phenotype. Source: BHF-UCL negative regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype. Source: BHF-UCL nucleobase-containing compound metabolic process Traceable author statement. Source: MGI protein homooligomerization Inferred from electronic annotation. Source: InterPro response to oxidative stress Inferred from direct assay. Source: MGI
Cellular component	Golgi apparatus Inferred from direct assay. Source: MGI anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum Inferred from direct assay. Source: MGI membrane raft Inferred from direct assay. Source: MGI plasma membrane Inferred from direct assay Ref.9. Source: UniProtKB
Molecular function	copper ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Chain

23 – 230

208

Major prion protein

PRO_0000025697

Propeptide

231 – 254

24

Removed in mature form By similarity

PRO_0000025698

Regions

Repeat

51 – 58

8

1

Repeat

59 – 66

8

2

Repeat

67 – 74

8

3

Repeat

75 – 82

8

4

Repeat

83 – 90

8

5

Region

23 – 231

209

Interaction with GRB2, ERI3 and SYN1

Region

51 – 90

40

5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q

Sites

Metal binding

60

1

Copper or zinc 1 By similarity

Metal binding

61

1

Copper or zinc 1; via amide nitrogen By similarity

Metal binding

62

1

Copper or zinc 1; via amide nitrogen and carbonyl oxygen By similarity

Metal binding

68

1

Copper or zinc 2 By similarity

Metal binding

69

1

Copper or zinc 2; via amide nitrogen By similarity

Metal binding

70

1

Copper or zinc 2; via amide nitrogen and carbonyl oxygen By similarity

Metal binding

76

1

Copper or zinc 3 By similarity

Metal binding

77

1

Copper or zinc 3; via amide nitrogen By similarity

Metal binding

78

1

Copper or zinc 3; via amide nitrogen and carbonyl oxygen By similarity

Metal binding

84

1

Copper or zinc 4 By similarity

Metal binding

85

1

Copper or zinc 4; via amide nitrogen By similarity

Metal binding

86

1

Copper or zinc 4; via amide nitrogen and carbonyl oxygen By similarity

Amino acid modifications

Modified residue

44

1

Hydroxyproline

Lipidation

230

1

GPI-anchor amidated serine By similarity

Glycosylation

180

1

N-linked (GlcNAc...) Probable

Glycosylation

196

1

N-linked (GlcNAc...) Ref.14

Disulfide bond

178 ↔ 213

Natural variations

Natural variant

108

1

L → F Linked to long incubation time.

Natural variant

189

1

T → V Linked to long incubation time.

Experimental info

Mutagenesis

101

1

P → L: No effect on interaction with GRB2. Ref.11

Mutagenesis

104

1

P → L: No effect on interaction with GRB2. Ref.11

Sequence conflict

133

1

M → V Ref.2

Sequence conflict

133

1

M → V Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

254

Helix Strand Turn

Details...

Turn

124 – 126

3

Beta strand

127 – 129

3

Helix

143 – 152

10

Turn

153 – 155

3

Beta strand

166 – 168

3

Helix

171 – 191

21

Turn

192 – 194

3

Helix

199 – 221

23

Turn

222 – 224

3

Sequences

	Sequence		Length	Mass (Da)
	P04925 [UniParc]. Last modified January 1, 1990. Version 2. Checksum: D5331E6321826CC0	FASTA	254	27,977
	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

References

	« Hide 'large scale' referencesShow '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: 2890436] [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: 3462700] [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: 2894984] [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: 9799790] [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: 15489334] [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: 3923361] [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: 8035877] [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: 8637886] [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: 9837873] [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: 11032800] [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: 11571277] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH GRB2; ERI3 AND SYN1, MUTAGENESIS OF PRO-101 AND PRO-104.
[12]	"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: 16492732] [Abstract] Cited for: DISRUPTION PHENOTYPE, GLYCOSYLATION, FUNCTION, TISSUE SPECIFICITY.
[13]	"Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegeneration." Chakrabarti O., Hegde R.S. Cell 137:1136-1147(2009) [PubMed: 19524515] [Abstract] Cited for: INTERACTION WITH MGRN1.
[14]	"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: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-196, MASS SPECTROMETRY.
[15]	"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: 19242475] [Abstract] Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH APP, FUNCTION.
[16]	"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: 19568430] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, GLYCOSYLATION, TISSUE SPECIFICITY.
[17]	"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: 19381258] [Abstract] Cited for: COPPER-BINDING.
[18]	"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: 20098419] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[19]	"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: 8700211] [Abstract] Cited for: STRUCTURE BY NMR OF 120-230.
[20]	"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: 9280298] [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.

IPI

IPI00120793.

PIR

A23544. A29669.

RefSeq

NP_035300.1. NM_011170.2.

UniGene

Mm.648.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AG2	NMR	-	A	123-225	[»]
1XYX	NMR	-	A	120-231	[»]
1Y15	NMR	-	A	120-231	[»]
1Y16	NMR	-	A	120-231	[»]
2K5O	NMR	-	A	120-231	[»]
2KFM	NMR	-	A	120-231	[»]
2KFO	NMR	-	A	120-231	[»]
2KU5	NMR	-	A	120-231	[»]
2KU6	NMR	-	A	120-231	[»]
2L1D	NMR	-	A	120-231	[»]
2L1E	NMR	-	A	120-231	[»]
2L1H	NMR	-	A	120-231	[»]
2L1K	NMR	-	A	120-231	[»]
2L39	NMR	-	A	120-231	[»]
2L40	NMR	-	A	120-231	[»]
3NVG	X-ray	1.48	A	137-142	[»]
3NVH	X-ray	1.61	A	137-143	[»]

ProteinModelPortal

P04925.

SMR

P04925. Positions 2-28, 89-232.

DisProt

DP00265.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-4N.

IntAct

P04925. 3 interactions.

MINT

MINT-214988.

STRING

P04925.

PTM databases

PhosphoSite

P04925.

Proteomic databases

PRIDE

P04925.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000091288; ENSMUSP00000088833; ENSMUSG00000079037.

GeneID

19122.

KEGG

mmu:19122.

Organism-specific databases

CTD

5621.

MGI

MGI:97769. Prnp.

Phylogenomic databases

eggNOG

roNOG07875.

HOGENOM

HBG278973.

HOVERGEN

HBG008260.

InParanoid

P04925.

OMA

PNQVYYR.

OrthoDB

EOG4HDSW2.

PhylomeDB

P04925.

Enzyme and pathway databases

Reactome

REACT_115492. Developmental Biology.

Gene expression databases

ArrayExpress

P04925.

Bgee

P04925.

CleanEx

MM_PRNP.

Genevestigator

P04925.

GermOnline

ENSMUSG00000027338. Mus musculus.

Family and domain databases

InterPro

IPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
[Graphical view]

Gene3D

G3DSA:1.10.790.10. Prion. 1 hit.

KO

K05634.

PANTHER

PTHR11522. Prion. 1 hit.

Pfam

PF00377. Prion. 1 hit.
[Graphical view]

PRINTS

PR00341. PRION.

SMART

SM00157. PRP. 1 hit.
[Graphical view]

SUPFAM

SSF54098. Prion. 1 hit.

PROSITE

PS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

295714.

PMAP-CutDB

P04925.

SOURCE

Search...

Entry information

Entry name

PRIO_MOUSE

Accession

Primary (citable) accession number: P04925

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 1, 1990
Last modified:	December 14, 2011
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program