InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRNP

Summary

InnateDB Protein

IDBP-49835.6

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

ENSP00000368752

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
GO:0005507	copper ion binding
GO:0005515	protein binding
GO:0008017	microtubule binding
GO:0015631	tubulin binding
GO:0042802	identical protein binding
GO:0043008	ATP-dependent protein binding
GO:0051087	chaperone binding

Biological Process

GO:0001933	negative regulation of protein phosphorylation
GO:0006878	cellular copper ion homeostasis
GO:0006979	response to oxidative stress
GO:0007050	cell cycle arrest
GO:0007411	axon guidance
GO:0007611	learning or memory
GO:0008152	metabolic process
GO:0032689	negative regulation of interferon-gamma production
GO:0032700	negative regulation of interleukin-17 production
GO:0032703	negative regulation of interleukin-2 production
GO:0032880	regulation of protein localization
GO:0043066	negative regulation of apoptotic process
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0046007	negative regulation of activated T cell proliferation
GO:0046686	response to cadmium ion
GO:0046688	response to copper ion
GO:0050860	negative regulation of T cell receptor signaling pathway
GO:0051260	protein homooligomerization
GO:0070885	negative regulation of calcineurin-NFAT signaling cascade
GO:1901379	regulation of potassium ion transmembrane transport

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0019898	extrinsic component of membrane
GO:0031225	anchored component of membrane
GO:0045121	membrane raft
GO:0070062	extracellular vesicular exosome