Reviewed, UniProtKB/Swiss-Prot P04925 (PRIO_MOUSE)

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

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 not known. PrP is encoded in the host genome and is expressed both in normal and infected cells.
Subunit structure	PrP has a tendency to aggregate yielding polymers called "rods". Interacts with GRB2, PRNPIP and SYN1. Ref.8
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Golgi apparatus. Ref.8
Tissue specificity	Highly expressed in the brain, lung, kidney and heart. Expressed at low levels in the liver and spleen.
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.
Sequence similarities	Belongs to the prion family.

Ontologies

Keywords
Cellular component	Cell membrane Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Disease	Prion
Domain	Repeat Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Hydroxylation Lipoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cellular copper ion homeostasis Traceable author statement. Source: MGI nucleobase, nucleoside, nucleotide and nucleic acid 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. Source: MGI
Molecular function	copper ion binding Inferred from direct assay. Source: MGI protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HNRNPA2B1	P22626	1	EBI-768613,EBI-299649	From a different organism.

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, PRNPIP and SYN1

Region

51 – 90

40

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

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...) Probable

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.8

Mutagenesis

104

1

P → L: No effect on interaction with GRB2. Ref.8

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)
	P04925-1 [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: NUCLEOTIDE 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. 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 OF 87-164.
[7]	"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.
[8]	"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; PRNPIP AND SYN1, MUTAGENESIS OF PRO-101 AND PRO-104.
[9]	"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.
[10]	"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

EMBLGenBankDDBJ

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.

UniGene

Mm.648

3D structure databases

PDBPDBe

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	[»]

DisProt

DP00265.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:4N.

IntAct

P04925. 3 interactions.

Proteomic databases

PRIDE

P04925.

Genome annotation databases

Ensembl

ENSMUSG00000079037. Mus musculus. [Contig view]

GeneID

19122.

KEGG

mmu:19122.

Organism-specific databases

MGI

MGI:97769. Prnp.

Phylogenomic databases

HOGENOM

P04925.

HOVERGEN

P04925.

OMA

P04925. PNQVYYR.

Gene expression databases

ArrayExpress

P04925.

Bgee

P04925.

CleanEx

MM_PRNP.

GermOnline

ENSMUSG00000027338. Mus musculus.

Family and domain databases

InterPro

IPR000817. Prion.
[Graphical view]

Gene3D

G3DSA:1.10.790.10. Prion. 1 hit.

PANTHER

PTHR11522. Prion. 1 hit.

Pfam

PF00377. Prion. 1 hit.
PF03991. Prion_octapep. 5 hits.
[Graphical view]

PRINTS

PR00341. PRION.

SMART

SM00157. PRP. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	June 16, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)