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Protein

Major prion protein

Gene

PRNP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor. 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). 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).By similarityCurated3 Publications

Miscellaneous

This protein is produced by a bicistronic gene which also produces the The alternative prion protein/AltPrP (AC F7VJQ1) from an overlapping reading frame.1 Publication
The alternative prion protein/AltPrP (AC F7VJQ1) and PRNP have no apparent direct functional relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of PRNP. In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi61Copper or zinc 11 Publication1
Metal bindingi62Copper or zinc 1; via amide nitrogen1 Publication1
Metal bindingi63Copper or zinc 1; via amide nitrogen and carbonyl oxygen1 Publication1
Metal bindingi69Copper or zinc 21 Publication1
Metal bindingi70Copper or zinc 2; via amide nitrogen1 Publication1
Metal bindingi71Copper or zinc 2; via amide nitrogen and carbonyl oxygen1 Publication1
Metal bindingi77Copper or zinc 31 Publication1
Metal bindingi78Copper or zinc 3; via amide nitrogen1 Publication1
Metal bindingi79Copper or zinc 3; via amide nitrogen and carbonyl oxygen1 Publication1
Metal bindingi85Copper or zinc 41 Publication1
Metal bindingi86Copper or zinc 4; via amide nitrogen1 Publication1
Metal bindingi87Copper or zinc 4; via amide nitrogen and carbonyl oxygen1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionPrion
Biological processCell cycle, Growth arrest
LigandCopper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-419037 NCAM1 interactions

Protein family/group databases

MoonDBiP04156 Predicted
TCDBi1.C.48.1.2 the prion peptide (prp) family

Names & Taxonomyi

Protein namesi
Recommended name:
Major prion protein
Short name:
PrP
Alternative name(s):
ASCR
PrP27-30
PrP33-35C
CD_antigen: CD230
Gene namesi
Name:PRNP
Synonyms:ALTPRP, PRIP, PRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000171867.16
HGNCiHGNC:9449 PRNP
MIMi176640 gene
neXtProtiNX_P04156

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Amyloid, Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

PrP is found in high quantity in the brain of humans and animals infected with neurodegenerative diseases known as transmissible spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in humans; scrapie in sheep and goat; bovine spongiform encephalopathy (BSE) in cattle; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of mule deer and elk; feline spongiform encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) in nyala and greater kudu. The prion diseases illustrate three manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to occur after consumption of prion-infected foodstuffs.1 Publication
Creutzfeldt-Jakob disease (CJD)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionOccurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness.
See also OMIM:123400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_006470180V → I in CJD. 3 PublicationsCorresponds to variant dbSNP:rs74315408EnsemblClinVar.1
Natural variantiVAR_008749196E → K in CJD. 1 Publication1
Natural variantiVAR_006473200E → K in CJD. 3 PublicationsCorresponds to variant dbSNP:rs28933385EnsemblClinVar.1
Natural variantiVAR_008751203V → I in CJD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776593792Ensembl.1
Natural variantiVAR_006474208R → H in CJD. 1 PublicationCorresponds to variant dbSNP:rs74315412EnsemblClinVar.1
Natural variantiVAR_006475210V → I in CJD. 1 PublicationCorresponds to variant dbSNP:rs74315407EnsemblClinVar.1
Natural variantiVAR_008752211E → Q in CJD. 1 PublicationCorresponds to variant dbSNP:rs398122370EnsemblClinVar.1
Natural variantiVAR_006478232M → R in CJD. 1 PublicationCorresponds to variant dbSNP:rs74315409EnsemblClinVar.1
Fatal familial insomnia (FFI)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia.
See also OMIM:600072
Gerstmann-Straussler disease (GSD)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain. GSD presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years.
See also OMIM:137440
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_006465105P → L in GSD. 2 PublicationsCorresponds to variant dbSNP:rs11538758EnsemblClinVar.1
Natural variantiVAR_014264131G → V in GSD. 1 PublicationCorresponds to variant dbSNP:rs74315410EnsemblClinVar.1
Natural variantiVAR_008746187H → R in GSD. 1 PublicationCorresponds to variant dbSNP:rs74315413EnsemblClinVar.1
Natural variantiVAR_006472198F → S in GSD; atypical form with neurofibrillary tangles. 1 PublicationCorresponds to variant dbSNP:rs74315405EnsemblClinVar.1
Natural variantiVAR_008750202D → N in GSD. 1 PublicationCorresponds to variant dbSNP:rs761807915