Version 5.4
Homo sapiens Protein: PRNP
Summary
InnateDB Protein IDBP-364815.4
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol PRNP
Protein Name prion protein
Synonyms AltPrP; ASCR; CD230; CJD; GSS; KURU; p27-30; PRIP; PrP; PrP27-30; PrP33-35C; PrPc;
Species Homo sapiens
Ensembl Protein ENSP00000415284
InnateDB Gene IDBG-49833 (PRNP)
Protein Structure
UniProt Annotation
Function 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 Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity). {ECO:0000250}.
Subcellular Localization 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 CU(2+), to vesicles in para- and perinuclear regions, where both proteins undergo internalization. Heparin displaces PRNP from lipid rafts and promotes endocytosis.Isoform 2: Cytoplasm. Nucleus. Note=Accumulates outside the secretory route in the cytoplasm, from where it relocates to the nucleus.
Disease Associations Note=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.Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs 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. {ECO:0000269PubMed:10790216, ECO:0000269PubMed:1671440, ECO:0000269PubMed:1975028, ECO:0000269PubMed:7902693, ECO:0000269PubMed:7906019, ECO:0000269PubMed:7913755, ECO:0000269PubMed:8461023, ECO:0000269PubMed:8909447, ECO:0000269PubMed:9266722}. Note=The disease is caused by mutations affecting the gene represented in this entry.Fatal familial insomnia (FFI) [MIM:600072]: Autosomal dominant disorder and is characterized by neuronal degeneration limited to selected thalamic nuclei and progressive insomnia. {ECO:0000269PubMed:1347910}. Note=The disease is caused by mutations affecting the gene represented in this entry.Gerstmann-Straussler disease (GSD) [MIM:137440]: A 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. {ECO:0000269PubMed:10581485, ECO:0000269PubMed:11709001, ECO:0000269PubMed:1363810, ECO:0000269PubMed:2564168, ECO:0000269PubMed:7699395, ECO:0000269PubMed:7783876, ECO:0000269PubMed:7902972, ECO:0000269PubMed:8797472, ECO:0000269PubMed:9786248}. Note=The disease is caused by mutations affecting the gene represented in this entry.Huntington disease-like 1 (HDL1) [MIM:603218]: Autosomal dominant, early-onset neurodegenerative disorder with prominent psychiatric features. Note=The disease is caused by mutations affecting the gene represented in this entry.Kuru (KURU) [MIM:245300]: Kuru is transmitted during ritualistic cannibalism, among natives of the New Guinea highlands. Patients exhibit various movement disorders like cerebellar abnormalities, rigidity of the limbs, and clonus. Emotional lability is present, and dementia is conspicuously absent. Death usually occurs from 3 to 12 month after onset. Note=The disease is caused by mutations affecting the gene represented in this entry.Spongiform encephalopathy with neuropsychiatric features (SENF) [MIM:606688]: Autosomal dominant presenile dementia with a rapidly progressive and protracted clinical course. The dementia was characterized clinically by frontotemporal features, including early personality changes. Some patients had memory loss, several showed aggressiveness, hyperorality and verbal stereotypy, others had parkinsonian symptoms. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 94 experimentally validated interaction(s) in this database.
They are also associated with 44 interaction(s) predicted by orthology.
Experimentally validated
Total 94 [view]
Protein-Protein 93 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 1 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 44 [view]
Gene Ontology

Molecular Function
Accession GO Term
Biological Process
GO:0051260 protein homooligomerization
Cellular Component
GO:0005886 plasma membrane
GO:0016020 membrane
Protein Structure and Domains
PDB ID
InterPro IPR000817 Prion protein
IPR022416 Prion/Doppel protein, beta-ribbon domain
IPR025860 Major prion protein N-terminal domain
PFAM PF00377
PF11587
PRINTS PR00341
PIRSF
SMART SM00157
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt
PhosphoSite PhosphoSite-P04156
TrEMBL X6RKS3
UniProt Splice Variant
Entrez Gene 5621
UniGene Hs.472010
RefSeq
HUGO HGNC:9449
OMIM 176640
CCDS
HPRD 01453
IMGT
EMBL AB300825 AL133396
GenPept BAG32278

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca