O18754 (PRIO_FELCA) 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

Felis catus (Cat) (Felis silvestris catus)

Taxonomic identifier

9685 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Feliformia › Felidae › Felinae › Felis

Protein attributes

Sequence length	256 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) 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=PrP is found in high quantity in the brain of humans and animals infected with the degenerative neurological diseases 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
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

By similarity

Chain

25 – 233

209

Major prion protein

PRO_0000025671

Propeptide

234 – 256

23

Removed in mature form Potential

PRO_0000025672

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 – 233

209

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

233

1

GPI-anchor amidated alanine Potential

Glycosylation

184

1

N-linked (GlcNAc...) Potential

Glycosylation

200

1

N-linked (GlcNAc...) Potential

Disulfide bond

182 ↔ 217

By similarity

Experimental info

Sequence conflict

64

1

H → HA in AAS94127. Ref.2

Sequence conflict

72

1

H → HA in AAS94127. Ref.2

Sequence conflict

80

1

H → HA in AAS94127. Ref.2

Sequence conflict

89

1

G → A in AAS94127. Ref.2

Sequence conflict

98 – 103

6

SHSQWN → GTHGQWG Ref.2

Sequence conflict

115

1

M → V Ref.1

Sequence conflict

115

1

M → V Ref.3

Sequence conflict

162

1

N → D Ref.3

Sequence conflict

180

1

H → R Ref.3

Sequence conflict

188

1

K → R in AAS94127. Ref.2

Sequence conflict

190

1

H → R Ref.1

Sequence conflict

190

1

H → R Ref.3

Sequence conflict

206

1

M → I in AAB70468. Ref.1

Sequence conflict

218

1

V → I in AAB70468. Ref.1

Sequence conflict

223

1

K → R in AAB70468. Ref.1

Sequence conflict

232

1

R → G in AAB70468. Ref.1

Sequence conflict

235

1

A → V in AAB70468. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

256

Helix Strand Turn

Details...

Helix

148 – 154

7

Helix

155 – 159

5

Beta strand

175 – 177

3

Helix

180 – 195

16

Helix

203 – 230

28

Sequences

	Sequence		Length	Mass (Da)
	O18754 [UniParc]. Last modified December 6, 2005. Version 3. Checksum: 09CCE931336C50E2	FASTA	256	27,968
	10 20 30 40 50 60 MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW 70 80 90 100 110 120 GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGSHS QWNKPSKPKT NMKHMAGAAA 130 140 150 160 170 180 AGAVVGGLGG YMLGSAMSRP LIHFGNDYED RYYRENMYRY PNQVYYRPVD QYSNQNNFVH 190 200 210 220 230 240 DCVNITVKQH TVTTTTKGEN FTETDMKIME RVVEQMCVTQ YQKESEAYYQ RRASAILFSS 250 PPVILLISFL IFLIVG

References

[1]	Rohwer R.G., Edelman D., Protzman J.L. Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood and Brain.
[2]	"Amino acid sequence of the Felis catus prion protein." Lysek D.A., Nivon L.G., Wuethrich K. Gene 341:249-253(2004) [PubMed: 15474307] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-234.
[3]	Taylor M.S., Newton D.J., Flanagan B.F., Christmas S.E. Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-235.
[4]	"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 104-214.
+	Additional computationally mapped references.

Web resources

Cat PRP

Web page on cat sequence problems

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF003087 Genomic DNA. Translation: AAB70468.1.
AY573555 Genomic DNA. Translation: AAS94127.1.
Y13698 Genomic DNA. Translation: CAA74032.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XYJ	NMR	-	A	124-234	[»]

ProteinModelPortal

O18754.

SMR

O18754. Positions 1-30, 124-234.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

HOVERGEN

HBG008260.

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.

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_FELCA

Accession

Primary (citable) accession number: O18754
Secondary accession number(s): O19016, Q5YCW7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	December 6, 2005
Last modified:	November 30, 2010
This is version 76 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program