P51446 · PRIO_ATEPA

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.

125220406080100120140160180200220240
TypeIDPosition(s)Description
Binding site60Cu2+ 1 (UniProtKB | ChEBI)
Binding site61Cu2+ 1 (UniProtKB | ChEBI)
Binding site62Cu2+ 1 (UniProtKB | ChEBI)
Binding site68Cu2+ 2 (UniProtKB | ChEBI)
Binding site69Cu2+ 2 (UniProtKB | ChEBI)
Binding site70Cu2+ 2 (UniProtKB | ChEBI)
Binding site76Cu2+ 3 (UniProtKB | ChEBI)
Binding site77Cu2+ 3 (UniProtKB | ChEBI)
Binding site78Cu2+ 3 (UniProtKB | ChEBI)
Binding site84Cu2+ 4 (UniProtKB | ChEBI)
Binding site85Cu2+ 4 (UniProtKB | ChEBI)
Binding site86Cu2+ 4 (UniProtKB | ChEBI)

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular ComponentGolgi apparatus
Cellular Componentplasma membrane
Cellular Componentside of membrane
Molecular Functioncopper ion binding
Biological Processprotein homooligomerization

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

Accessions

  • Primary accession
    P51446

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_000002561723-229Major prion protein
Disulfide bond178↔213
Glycosylation180N-linked (GlcNAc...) asparagine
Glycosylation196N-linked (GlcNAc...) asparagine
Lipidation229GPI-anchor amidated serine
PropeptidePRO_0000025618230-252Removed in mature form

Keywords

PTM 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.

Structure

Family & Domains

Features

Showing features for region, repeat.

TypeIDPosition(s)Description
Region23-229Interaction with GRB2, ERI3 and SYN1
Region26-104Disordered
Repeat51-581
Region51-905 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q
Repeat59-662
Repeat67-743
Repeat75-824
Repeat83-905

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

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    252
  • Mass (Da)
    27,718
  • Last updated
    1996-10-01 v1
  • Checksum
    20EA38A42DCC56D1
MANLGYWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQAGGTHNQWNKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYEDRYYRENMYRYPNQVYYRPVDQYNNQNNFVHDCVNITIKQHTVTTTTKGENLTETDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSSPPVILLISFLIFLIVG

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U15164
EMBL· GenBank· DDBJ
AAA68634.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp