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O46501 (PRIO_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified September 21, 2011. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Major prion protein
Short name=PrP
Alternative name(s):
CD_antigen=CD230
Gene names
Name:PRNP
Synonyms:PRP
OrganismCanis familiaris (Dog) (Canis lupus familiaris)
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

Protein attributes

Sequence length255 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 By similarity
Chain25 – 232208Major prion protein
PRO_0000025639
Propeptide233 – 25523Removed in mature form Potential
PRO_0000025640

Regions

Repeat54 – 6291
Repeat63 – 7082
Repeat71 – 7883
Repeat79 – 8684
Repeat87 – 9485
Region25 – 232208Interaction with GRB2, ERI3 and SYN1 By similarity
Region54 – 94415 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q

Sites

Metal binding641Copper or zinc 1 By similarity
Metal binding651Copper or zinc 1; via amide nitrogen By similarity
Metal binding661Copper or zinc 1; via amide nitrogen and carbonyl oxygen By similarity
Metal binding721Copper or zinc 2 By similarity
Metal binding731Copper or zinc 2; via amide nitrogen By similarity
Metal binding741Copper or zinc 2; via amide nitrogen and carbonyl oxygen By similarity
Metal binding801Copper or zinc 3 By similarity
Metal binding811Copper or zinc 3; via amide nitrogen By similarity
Metal binding821Copper or zinc 3; via amide nitrogen and carbonyl oxygen By similarity
Metal binding881Copper or zinc 4 By similarity
Metal binding891Copper or zinc 4; via amide nitrogen By similarity
Metal binding901Copper or zinc 4; via amide nitrogen and carbonyl oxygen By similarity

Amino acid modifications

Lipidation2321GPI-anchor amidated alanine Potential
Glycosylation1741N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Potential
Glycosylation1991N-linked (GlcNAc...) Potential
Disulfide bond182 ↔ 216 By similarity

Secondary structure

1 ............ 255
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O46501 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 70E80411BD6B1F63

FASTA25527,704
        10         20         30         40         50         60 
MVKSHIGSWI LVLFVAMWSD VGLCKKRPKP GGGWNTGGSR YPGQGSPGGN RYPPQGGGGW 

        70         80         90        100        110        120 
GQPHGGGWGQ PHGGGWGQPH GGGWGQPHGG GGWGQGGTHS QWNKPSKPKT NMKHVAGAAA 

       130        140        150        160        170        180 
AGAVVGGLGG YLLGSAMSRP LIHFGNDCED RYYRENMYRY PNQVYYRSVD QYNNQSTFVH 

       190        200        210        220        230        240 
DCVNITVKQH TVTTTKGENF TETDIKMMER VVEQMCITQY QRESEAYYQR GASVILFSSP 

       250 
PVILLVSFLI FLIVG

« Hide

References

[1]Rohwer R.G., Edelman D.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
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 124-233.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF022714 Genomic DNA. Translation: AAB94585.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XYKNMR-A124-233[»]
ProteinModelPortalO46501.
SMRO46501. Positions 1-30, 124-233.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG008260.
InParanoidO46501.

Family and domain databases

InterProIPR000817. Prion.
IPR022416. Prion/Doppel_prot_b-ribbon_dom.
[Graphical view]
Gene3DG3DSA:1.10.790.10. Prion. 1 hit.
PANTHERPTHR11522. Prion. 1 hit.
PfamPF00377. Prion. 1 hit.
[Graphical view]
PRINTSPR00341. PRION.
SMARTSM00157. PRP. 1 hit.
[Graphical view]
SUPFAMSSF54098. Prion. 1 hit.
PROSITEPS00291. PRION_1. 1 hit.
PS00706. PRION_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry namePRIO_CANFA
AccessionPrimary (citable) accession number: O46501
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: September 21, 2011
This is version 75 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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