UniProtKB - P04156 (PRIO_HUMAN)
Protein
Major prion protein
Gene
PRNP
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Metal bindingi | 61 | Copper or zinc 11 Publication | 1 | |
| Metal bindingi | 62 | Copper or zinc 1; via amide nitrogen1 Publication | 1 | |
| Metal bindingi | 63 | Copper or zinc 1; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
| Metal bindingi | 69 | Copper or zinc 21 Publication | 1 | |
| Metal bindingi | 70 | Copper or zinc 2; via amide nitrogen1 Publication | 1 | |
| Metal bindingi | 71 | Copper or zinc 2; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
| Metal bindingi | 77 | Copper or zinc 31 Publication | 1 | |
| Metal bindingi | 78 | Copper or zinc 3; via amide nitrogen1 Publication | 1 | |
| Metal bindingi | 79 | Copper or zinc 3; via amide nitrogen and carbonyl oxygen1 Publication | 1 | |
| Metal bindingi | 85 | Copper or zinc 41 Publication | 1 | |
| Metal bindingi | 86 | Copper or zinc 4; via amide nitrogen1 Publication | 1 | |
| Metal bindingi | 87 | Copper or zinc 4; via amide nitrogen and carbonyl oxygen1 Publication | 1 |
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- ATP-dependent protein binding Source: Ensembl
- chaperone binding Source: Ensembl
- copper ion binding Source: UniProtKB
- cupric ion binding Source: Ensembl
- cuprous ion binding Source: CAFA
- glycosaminoglycan binding Source: ARUK-UCL
- identical protein binding Source: CAFA
- ion channel binding Source: Ensembl
- lamin binding Source: Ensembl
- microtubule binding Source: UniProtKB
- protease binding Source: ARUK-UCL
- protein-containing complex binding Source: ARUK-UCL
- signaling receptor activity Source: ARUK-UCL
- tubulin binding Source: UniProtKB
- type 5 metabotropic glutamate receptor binding Source: ARUK-UCL
GO - Biological processi
- activation of protein kinase activity Source: Ensembl
- calcium-mediated signaling using intracellular calcium source Source: ARUK-UCL
- cell cycle arrest Source: UniProtKB-KW
- cellular copper ion homeostasis Source: UniProtKB
- cellular response to amyloid-beta Source: ARUK-UCL
- cellular response to copper ion Source: MGI
- cellular response to drug Source: Ensembl
- dendritic spine maintenance Source: ARUK-UCL
- learning or memory Source: ARUK-UCL
- long-term memory Source: ARUK-UCL
- modulation of age-related behavioral decline Source: ARUK-UCL
- negative regulation of activated T cell proliferation Source: BHF-UCL
- negative regulation of amyloid-beta formation Source: ARUK-UCL
- negative regulation of amyloid precursor protein catabolic process Source: ARUK-UCL
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of calcineurin-NFAT signaling cascade Source: BHF-UCL
- negative regulation of catalytic activity Source: Ensembl
- negative regulation of dendritic spine maintenance Source: ARUK-UCL
- negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
- negative regulation of interferon-gamma production Source: BHF-UCL
- negative regulation of interleukin-17 production Source: BHF-UCL
- negative regulation of interleukin-2 production Source: BHF-UCL
- negative regulation of long-term synaptic potentiation Source: Ensembl
- negative regulation of protein phosphorylation Source: BHF-UCL
- negative regulation of protein processing Source: ARUK-UCL
- negative regulation of T cell receptor signaling pathway Source: BHF-UCL
- neuron projection maintenance Source: ARUK-UCL
- positive regulation of neuron apoptotic process Source: CAFA
- positive regulation of neuron death Source: ARUK-UCL
- positive regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCL
- positive regulation of protein localization to plasma membrane Source: Ensembl
- positive regulation of protein targeting to membrane Source: ARUK-UCL
- positive regulation of protein tyrosine kinase activity Source: ARUK-UCL
- protein destabilization Source: CAFA
- protein homooligomerization Source: CAFA
- regulation of calcium ion import across plasma membrane Source: ARUK-UCL
- regulation of glutamate receptor signaling pathway Source: ARUK-UCL
- regulation of intracellular calcium activated chloride channel activity Source: ARUK-UCL
- regulation of peptidyl-tyrosine phosphorylation Source: ARUK-UCL
- regulation of potassium ion transmembrane transport Source: Ensembl
- response to amyloid-beta Source: ARUK-UCL
- response to cadmium ion Source: Ensembl
- response to oxidative stress Source: UniProtKB
Keywordsi
| Molecular function | Prion |
| Biological process | Cell cycle, Growth arrest |
| Ligand | Copper, Metal-binding, Zinc |
Enzyme and pathway databases
| Reactomei | R-HSA-419037 NCAM1 interactions |
Protein family/group databases
| MoonDBi | P04156 Predicted |
| TCDBi | 1.C.48.1.2 the prion peptide (prp) family |
Names & Taxonomyi
| Protein namesi | Recommended name: Major prion proteinShort name: PrP Alternative name(s): ASCR PrP27-30 PrP33-35C CD_antigen: CD230 |
| Gene namesi | Name:PRNP Synonyms:ALTPRP, PRIP, PRP |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000171867.16 |
| HGNCi | HGNC:9449 PRNP |
| MIMi | 176640 gene |
| neXtProti | NX_P04156 |
Subcellular locationi
Keywords - Cellular componenti
Amyloid, Cell membrane, Cytoplasm, Golgi apparatus, Membrane, NucleusPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_006470 | 180 | V → I in CJD. 3 PublicationsCorresponds to variant dbSNP:rs74315408EnsemblClinVar. | 1 | |
| Natural variantiVAR_008749 | 196 | E → K in CJD. 1 Publication | 1 | |
| Natural variantiVAR_006473 | 200 | E → K in CJD. 3 PublicationsCorresponds to variant dbSNP:rs28933385EnsemblClinVar. | 1 | |
| Natural variantiVAR_008751 | 203 | V → I in CJD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs776593792Ensembl. | 1 | |
| Natural variantiVAR_006474 | 208 | R → H in CJD. 1 PublicationCorresponds to variant dbSNP:rs74315412EnsemblClinVar. | 1 | |
| Natural variantiVAR_006475 | 210 | V → I in CJD. 1 PublicationCorresponds to variant dbSNP:rs74315407EnsemblClinVar. | 1 | |
| Natural variantiVAR_008752 | 211 | E → Q in CJD. 1 PublicationCorresponds to variant dbSNP:rs398122370EnsemblClinVar. | 1 | |
| Natural variantiVAR_006478 | 232 | M → 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:600072Gerstmann-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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_006465 | 105 | P → L in GSD. 2 PublicationsCorresponds to variant dbSNP:rs11538758EnsemblClinVar. | 1 | |
| Natural variantiVAR_014264 | 131 | G → V in GSD. 1 PublicationCorresponds to variant dbSNP:rs74315410EnsemblClinVar. | 1 | |
| Natural variantiVAR_008746 | 187 | H → R in GSD. 1 PublicationCorresponds to variant dbSNP:rs74315413EnsemblClinVar. | 1 | |
| Natural variantiVAR_006472 | 198 | F → S in GSD; atypical form with neurofibrillary tangles. 1 PublicationCorresponds to variant dbSNP:rs74315405EnsemblClinVar. | 1 | |
| Natural variantiVAR_008750 | 202 | D → N in GSD. 1 PublicationCorresponds to variant dbSNP:rs761807915 |