P67997 · PRIO_MACMU

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.

125320406080100120140160180200220240
TypeIDPosition(s)Description
Binding site61Cu2+ 1 (UniProtKB | ChEBI)
Binding site62Cu2+ 1 (UniProtKB | ChEBI)
Binding site63Cu2+ 1 (UniProtKB | ChEBI)
Binding site69Cu2+ 2 (UniProtKB | ChEBI)
Binding site70Cu2+ 2 (UniProtKB | ChEBI)
Binding site71Cu2+ 2 (UniProtKB | ChEBI)
Binding site77Cu2+ 3 (UniProtKB | ChEBI)
Binding site78Cu2+ 3 (UniProtKB | ChEBI)
Binding site79Cu2+ 3 (UniProtKB | ChEBI)
Binding site85Cu2+ 4 (UniProtKB | ChEBI)
Binding site86Cu2+ 4 (UniProtKB | ChEBI)
Binding site87Cu2+ 4 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcell surface
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentendoplasmic reticulum
Cellular ComponentGolgi apparatus
Cellular Componentinclusion body
Cellular Componentmembrane raft
Cellular Componentnuclear membrane
Cellular Componentplasma membrane
Cellular Componentside of membrane
Cellular Componentterminal bouton
Molecular Functionamyloid-beta binding
Molecular Functionaspartic-type endopeptidase inhibitor activity
Molecular Functioncopper ion binding
Molecular Functioncupric ion binding
Molecular Functioncuprous ion binding
Molecular Functionglycosaminoglycan binding
Molecular Functionidentical protein binding
Molecular Functionmicrotubule binding
Molecular Functionmolecular condensate scaffold activity
Molecular Functionmolecular function activator activity
Molecular Functionprotease binding
Molecular Functionprotein-containing complex binding
Molecular Functionsignaling receptor activity
Molecular Functiontype 5 metabotropic glutamate receptor binding
Biological Processcellular response to amyloid-beta
Biological Processcellular response to copper ion
Biological Processcellular response to xenobiotic stimulus
Biological Processlearning or memory
Biological Processnegative regulation of activated T cell proliferation
Biological Processnegative regulation of amyloid-beta formation
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of calcineurin-NFAT signaling cascade
Biological Processnegative regulation of dendritic spine maintenance
Biological Processnegative regulation of interleukin-17 production
Biological Processnegative regulation of interleukin-2 production
Biological Processnegative regulation of protein phosphorylation
Biological Processnegative regulation of T cell receptor signaling pathway
Biological Processnegative regulation of type II interferon production
Biological Processneuron projection maintenance
Biological Processpositive regulation of neuron apoptotic process
Biological Processpositive regulation of peptidyl-tyrosine phosphorylation
Biological Processpositive regulation of protein localization to plasma membrane
Biological Processpositive regulation of protein targeting to membrane
Biological Processprotein destabilization
Biological Processprotein homooligomerization
Biological Processregulation of calcium ion import across plasma membrane
Biological Processregulation of glutamate receptor signaling pathway
Biological Processregulation of potassium ion transmembrane transport
Biological Processresponse to oxidative stress

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Major prion protein
  • Short names
    PrP
  • Alternative names
    • PrP27-30
    • PrP33-35C
  • CD Antigen Name
    • CD230

Gene names

    • Name
      PRNP
    • Synonyms
      PRP

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Macaca

Accessions

  • Primary accession
    P67997
  • Secondary accessions
    • P40254

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Lipid-anchor, GPI-anchor
Golgi apparatus
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

Phenotypes & Variants

Involvement in disease

  • 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

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation, lipidation, propeptide.

TypeIDPosition(s)Description
Signal1-22
ChainPRO_000002568923-230Major prion protein
Disulfide bond179↔214
Glycosylation181N-linked (GlcNAc...) asparagine
Glycosylation197N-linked (GlcNAc...) asparagine
Lipidation230GPI-anchor amidated serine
PropeptidePRO_0000025690231-253Removed in mature form

Keywords

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.

TypeIDPosition(s)Description
Region23-230Interaction with GRB2, ERI3 and SYN1
Region26-108Disordered
Repeat51-591
Region51-915 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q
Repeat60-672
Repeat68-753
Repeat76-834
Repeat84-915

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

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    253
  • Mass (Da)
    27,676
  • Last updated
    2004-10-11 v1
  • Checksum
    F01D5EA64AB68C31
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHNQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYEKESQAYYQRGSSMVLFSSPPVILLISFLIFLIVG

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U15163
EMBL· GenBank· DDBJ
AAA68635.1
EMBL· GenBank· DDBJ
Genomic DNA
U08307
EMBL· GenBank· DDBJ
AAC50095.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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