P49927 (PRIO_PIG) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Major prion protein
Short name=PrP

Alternative name(s):
CD_antigen=CD230

Gene names

Name:	PRNP
Synonyms:	PRP

Organism

Sus scrofa (Pig) [Complete proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	257 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 By similarity. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) By similarity.
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 APP, GRB2, ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Golgi apparatus By similarity.
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.
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.
Sequence similarities	Belongs to the prion family.

Ontologies

Keywords
Cellular component	Amyloid Cell membrane Golgi apparatus Membrane
Domain	Repeat Signal
Ligand	Copper Metal-binding Zinc
Molecular function	Prion
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	protein homooligomerization Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
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 – 24

24

Potential

Chain

25 – 234

210

Major prion protein

PRO_0000025715

Propeptide

235 – 257

23

Removed in mature form Potential

PRO_0000025716

Regions

Repeat

54 – 62

9

1

Repeat

63 – 70

8

2

Repeat

71 – 78

8

3

Repeat

79 – 86

8

4

Repeat

87 – 95

9

5

Region

25 – 234

210

Interaction with GRB2, ERI3 and SYN1 By similarity

Region

54 – 95

42

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

Sites

Metal binding

64

1

Copper or zinc 1 By similarity

Metal binding

65

1

Copper or zinc 1; via amide nitrogen By similarity

Metal binding

66

1

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

Metal binding

72

1

Copper or zinc 2 By similarity

Metal binding

73

1

Copper or zinc 2; via amide nitrogen By similarity

Metal binding

74

1

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

Metal binding

80

1

Copper or zinc 3 By similarity

Metal binding

81

1

Copper or zinc 3; via amide nitrogen By similarity

Metal binding

82

1

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

Metal binding

88

1

Copper or zinc 4 By similarity

Metal binding

89

1

Copper or zinc 4; via amide nitrogen By similarity

Metal binding

90

1

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

Amino acid modifications

Lipidation

234

1

GPI-anchor amidated alanine Potential

Glycosylation

185

1

N-linked (GlcNAc...) Potential

Glycosylation

201

1

N-linked (GlcNAc...) Potential

Disulfide bond

183 ↔ 218

Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

257

Helix Strand Turn

Details...

Helix

150 – 153

4

Helix

155 – 160

6

Helix

177 – 196

20

Helix

204 – 229

26

Sequences

	Sequence		Length	Mass (Da)
	P49927 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 3A87104B234C55DD	FASTA	257	27,727
	10 20 30 40 50 60 MVKSHIGGWI LVLFVAAWSD IGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW 70 80 90 100 110 120 GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGGSH GQWNKPSKPK TNMKHVAGAA 130 140 150 160 170 180 AAGAVVGGLG GYMLGSAMSR PLIHFGSDYE DRYYRENMYR YPNQVYYRPV DQYSNQNSFV 190 200 210 220 230 240 HDCVNITVKQ HTVTTTTKGE NFTETDVKMI ERVVEQMCIT QYQKEYEAYA QRGASVILFS 250 SPPVILLISF LLFLIVG

References

[1]	"Direct sequencing of PCR amplified pig PrP genes." Martin T., Hughes S., Hughes K., Dawson M. Biochim. Biophys. Acta 1270:211-214(1995) [PubMed: 7727546] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Prion protein NMR structures of cats, dogs, pigs, and sheep." Lysek D.A., Schorn C., Nivon L.G., Esteve-Moya V., Christen B., Calzolai L., von Schroetter C., Fiorito F., Herrmann T., Guentert P., Wuethrich K. Proc. Natl. Acad. Sci. U.S.A. 102:640-645(2005) [PubMed: 15647367] [Abstract] Cited for: STRUCTURE BY NMR OF 125-235, DISULFIDE BOND.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L07623 Genomic DNA. Translation: AAA92862.1.

RefSeq

NP_001008687.1. NM_001008687.1.

UniGene

Ssc.6371.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XYQ	NMR	-	A	125-235	[»]

ProteinModelPortal

P49927.

SMR

P49927. Positions 1-30, 125-235.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49927. 2 interactions.

STRING

P49927.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSSSCT00000007708; ENSSSCP00000007501; ENSSSCG00000007039.

GeneID

494014.

KEGG

ssc:494014.

Organism-specific databases

CTD

5621.

Phylogenomic databases

HOVERGEN

HBG008260.

OMA

PNQVYYR.

OrthoDB

EOG4HDSW2.

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...

Entry information

Entry name

PRIO_PIG

Accession

Primary (citable) accession number: P49927

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 16, 2011
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program