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FLASH GENE

Symbol

PRNP

contributors: mct/shn - updated : 26-12-2013

HGNC name	prion protein
HGNC id	9449

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide of 22 AA
	four sequential copies of the five tandem octapeptide repeats highly instable
	two hydrophobic segments
	two possible sites for N glycosylation
	five tandem octapeptide repeats highly instable
	an active domain requiring certain regions such as the Cu-binding octameric repeat region and the hydrophobic core
	C terminal hydrophobic region TM2 functioning as second signal sequence

secondary structure

alpha helical conformation with a single disulfide bond linking CYS residues at 179 and 214 position

conjugated

GlycoP , Other

HOMOLOGY

interspecies	ortholog to Prnp, Mus musculus
	ortholog to Prnp, Rattus norvegicus
	ortholog to prnp, Danio rerio
	ortholog to PRNP, Pan troglodytes

intraspecies

homolog to PRNP

Homologene

FAMILY

prion family

CATEGORY

regulatory , signaling neurotransmitter

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
text	glycosylphosphatidylinositol-anchored cell-surface protein
	PrPC mutants, PrP145stop and PrP160stop were detected in the nucleus when expressed in neuroblastoma cells ,

basic FUNCTION	may be a signal transduction protein
	potent anti-apoptotic protein against BAX-mediated cell-death
	Cu-binding protein and normal function requires Cu-binding
	playing a role in the formation of long-term memory
	having a neuroprotective activity against apoptosis
	playing a role in copper homeostasis
	essential for myelin maintenance ,
	a mediator of Amyloid beta toxicity
	interaction between the middle region of PRNP and lipids is essential for the formation of its conformation, and role of alteration of this interaction in the pathogenesis of prion disease
	enhancing of the phagocytotic activity in PRNP-deficient macrophage cells
	involved in T lymphocytes response to oxidative stress, and having a protective function in thymocytes against oxidative stress
	anchored PRNP is an essential component for the rapid neural spread and CNS neuroinvasion of prion infection

CELLULAR PROCESS	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

neurotransmission

neuronal transmission

a component

INTERACTION

DNA	DNA molecules

RNA	RNA molecules ,

small molecule	metal binding,
	Cu2+
	unilamellar vesicles containing phosphatidylserine
	phosphatidylglycerol and phosphatidylserine
	Hemin (iron protoporphyrin IX)

protein	heat shock protein 60, Hsp60
	casein kinase 2, CK2
	plasminogen
	neuronal phosphoprotein synapsin Ib, Grb2, and Pint1
	stress-inducible protein 1, STI1
	heparin
	tubulin
	heterogeneous nuclear ribonucleoprotein A2/B1 and aldolase C
	lipoprotein receptor-related protein 1, LRP1
	clusterin
	Abeta42 oligomers
	ADAM23
	STIP1 (PMID :
	kinesin and dynein
	Hsp70
	thiamine
	KCTD1 is a molecular interaction partners of the cellular prion protein (PRNP)
	ADAM8 can perform alpha-cleavage of PRNP and PRNP can regulate ADAM8 expression
	amyloid-beta precursor protein
	FOXO3 negatively regulates PRNP expression by binding to the PRNP promoter, which is negatively regulated by insulin-like growth factor 1 (IGF1)
	interacts with BECN1 to recruit the PIK3C3 complex into lipid rafts and thus activates autophagy in response to Abeta42, defining a novel role of PRNP in the regulation of autophagy
	AMFR is critical for unglycosylated PRNP ubiquitylation and degradation

cell & other

REGULATION

activated by

ATOX1, a transcription factor that upregulates prion protein expression

Other

endoproteolytic alpha-cleavage of cellular prion protein (PRNP) regulates PRNP toxicity and functions

ASSOCIATED DISORDERS

corresponding disease(s)

CJD , GSSS , IDTF , HDL1 , EOD

related resource

Prion Protein/CJD database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function by misfolded prion protein in sudden infant death syndrome (SIDS) constitutional     --over   in ischemic brain damage tumoral     --over   in gastric cancer tissues (ectopic expression of PRNP could promote tumorigenesis, proliferation, and G1/S transition in gastric cancer cells) constitutional     --other   altered expression levels may play an important role in susceptibility to infection tumoral     --over   may constitute a prognostic marker for colorectal cancerrecurrence

Susceptibility

for Creutzfeldt-Jakob disease to fatal familial insomnia to Alzheimer disease-like tau disease

Variant & Polymorphism SNP	strong susceptibility factor for PRNP disease (sporadic CJD)
	SNP M129V increasing the risk of Creutzfeldt-Jakob disease
	SNP M129M or M129V increasing the long-term memory, and associated to a fatal familial insomnia
	rare PRNP mutation (Q160X) that resulted in the production of truncated PRNP, associated to Alzheimer disease-like tau disease

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive colon target for anticancer therapy

ANIMAL & CELL MODELS

	mice expressing DeltaPrP or Dpl suffer from widespread leukoencephalopathy
	mouse expressing the PrP(DeltaCD), a PrP variant lacking 40 central residues, displays a rapidly progressive, lethal phenotype with extensive central and peripheral myelin degeneration
	ablation of the prion protein PrP(C) triggers a chronic demyelinating polyneuropathy in four independently targeted mouse strains
	absence of PrPC in a transgenic Alzheimer mouse rescues deficits in spatial learning and memory
	Knockdown PRNP homolog in the zebrafish leads to a dose-dependent phenotype characterized by systemic morphological defects, reduced cell adhesion and CNS cell death