P67997 · PRIO_MACMU
- ProteinMajor prion protein
- GenePRNP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids253 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. 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). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu2+ or Zn2+ for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 61 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 62 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 63 | Cu2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 69 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 70 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 71 | Cu2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 77 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 78 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 79 | Cu2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 85 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 86 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 87 | Cu2+ 4 (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
Keywords
- Molecular function
- Ligand
Names & Taxonomy
Protein names
- Recommended nameMajor prion protein
- Short namesPrP
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca
Accessions
- Primary accessionP67997
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor, GPI-anchor
Note: Targeted to lipid rafts via association with the heparan sulfate chains of GPC1. Colocates, in the presence of Cu2+, to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis.
Keywords
- Cellular component
Phenotypes & Variants
Involvement in disease
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, lipidation, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-22 | |||||
Sequence: MANLGCWMLVLFVATWSDLGLC | ||||||
Chain | PRO_0000025689 | 23-230 | Major prion protein | |||
Sequence: KKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGS | ||||||
Disulfide bond | 179↔214 | |||||
Sequence: CVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMC | ||||||
Glycosylation | 181 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 197 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Lipidation | 230 | GPI-anchor amidated serine | ||||
Sequence: S | ||||||
Propeptide | PRO_0000025690 | 231-253 | Removed in mature form | |||
Sequence: SMVLFSSPPVILLISFLIFLIVG |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
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. Interacts with KIAA1191.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 23-230 | Interaction with GRB2, ERI3 and SYN1 | ||||
Sequence: KKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGS | ||||||
Region | 26-108 | Disordered | ||||
Sequence: PKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTS | ||||||
Repeat | 51-59 | 1 | ||||
Sequence: PQGGGGWGQ | ||||||
Region | 51-91 | 5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q | ||||
Sequence: PQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQ | ||||||
Repeat | 60-67 | 2 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 68-75 | 3 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 76-83 | 4 | ||||
Sequence: PHGGGWGQ | ||||||
Repeat | 84-91 | 5 | ||||
Sequence: PHGGGWGQ |
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.
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.
Sequence similarities
Belongs to the prion family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length253
- Mass (Da)27,676
- Last updated2004-10-11 v1
- ChecksumF01D5EA64AB68C31
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U15163 EMBL· GenBank· DDBJ | AAA68635.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U08307 EMBL· GenBank· DDBJ | AAC50095.1 EMBL· GenBank· DDBJ | Genomic DNA |