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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
    Physical map
    C20orf28 20pter-q11.23 chromosome 20 open reading frame 28 CENPB 20p13 centromere protein B, 80kDa CDC25B 20p13 cell division cycle 25B C20orf29 20p13 chromosome 20 open reading frame 29 KIAA1271 20p13 KIAA1271 protein PANK2 20p13 pantothenate kinase 2 (Hallervorden-Spatz syndrome) RNF24 20p13-p12.1 ring finger protein 24 LOC388783 20 similar to hypothetical protein RPL21P2 20p13 ribosomal protein L21 pseudogene 2 MGC34919 20p13 hypothetical protein MGC34919 SMOX 20p13 spermine oxidase ADRA1D 20p13 adrenergic, alpha-1D-, receptor RPL7AL2 20p13 ribosomal protein L7a like 2 RPS4L2 20p13 ribosomal protein S4-like 2 PRNP 20p12.3 prion protein (p27-30) (Creutzfeld-Jakob disease, Gerstmann-Strausler-Scheinker syndrome, fatal familial insomnia) PRND 20pter-p12 prion protein 2 (dublet) LOC149830 20p13 M8 protein RASSF2 20pter-p12.1 Ras association (RalGDS/AF-6) domain family 2 SLC23A2 5q31.2-q31.3 solute carrier family 23 (nucleobase transporters), member 2 C20orf30 20p13 chromosome 20 open reading frame 30 PCNA 20p12.3 proliferating cell nuclear antigen CDS2 20p13 CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2 LOC388784 20 similar to dJ680N4.2 (ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5)) GPR73L1 20p13 G protein-coupled receptor 73-like 1 LOC388785 20 hypothetical gene supported by AK090863 MGC35023 20p13 hypothetical protein MGC35023
    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