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FLASH GENE
Symbol PRNP contributors: mct/shn - updated : 26-12-2013
HGNC name prion protein
HGNC id 9449
Corresponding disease
CJD Creutzfeldt-Jakob disease
EOD early onset (median age), dementia
GSSS Gerstmann-Sträussler-Scheinker disease
HDL1 Huntington-like 1
IDTF insomnia-dysautonomia thalamic syndrome
Location 20p13      Physical location : 4.666.796 - 4.682.233
Synonym name
  • prion related protein
  • CD230 antigen
  • major prion protein
  • prion protein (p27-30)
  • Creutzfeldt-Jakob disease
  • fatal familial insomnia
  • Gerstmann-Strausler-Scheinker syndrome
    • Synonym symbol(s) PRIP, PRP, PRPC, PrPc, ASCR, CD230, CJD, GSS, MGC26679, p27-30, PrP27-30, PrP33-35C, AltPrP, CD230, KURU
    DNA
    TYPE functioning gene
    STRUCTURE 15.44 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site
    motif repetitive sequence
    text structure
  • Sp1-Ap1, AP2 binding sites
  • region within intron 1 sufficient to drive prion protein expression, with two potential repressor regions, having binding sites for HES1 (overexpression of HES1caused a dramatic decrease in protein expression)
  • a downstream alternative translation initiation AUG codon surrounded by an optimal Kozak sequence in the +3 reading frame of PRNP
    • MAPPING cloned Y linked Y status confirmed
    Map pter - D20S1149 - D20S97 - PRNP - D20S895 - D20S849 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 splicing 2755 27.6 253 - 1986 3014653
    2 splicing 2751 27.6 253 - -
    using an alternate splice site in the 5'UTR
    2 splicing 2750 - 253 - -
    2 splicing 2746 - 253 - -
    2 splicing 2619 - 253 - -
    - - - 18.5 - - 2008 18753138
  • primary N-terminal sequence with types 1 and 2 but lacking the very end of the C terminus together with the GPI anchor
  • asssociated with Creutzfeld-Jakob disease
    • - - - 17 - - 2008 18753138
    asssociated with Creutzfeld-Jakob disease
    - - - - 20 - 2008 18753138
    asssociated with Creutzfeld-Jakob disease, only in typical sporadic forms
    - - - - - . localized at the mitochondria . brain, primary neurons, and peripheral blood mononuclear cells 2011 21478263
  • completely different amino acid sequence from PRNP
  • up-regulated by endoplasmic reticulum stress and proteasomal inhibition
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticerythroid    
    Endocrinepancreas   highly
    Nervousbrain   highly Homo sapiens
    Reproductivefemale systemovary   
     male systemprostate   
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Nervouscentral  highly Homo sapiens
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    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