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FLASH GENE
Symbol PSENEN contributors: mct - updated : 14-03-2018
HGNC name presenilin enhancer gamma-secretase subunit
HGNC id 30100
Corresponding disease
ACNINV2 acne inversa, familial, 2, with or without Dowling-Degos disease
Location 19q13.12      Physical location : 36.236.493 - 36.237.903
Synonym name
  • hematopoietic stem/progenitor cells protein MDS033
  • gamma-secretase subunit PEN-2
    • Synonym symbol(s) MDS033, MSTP064, PEN2, PEN-2, ACNINV2
    DNA
    TYPE functioning gene
    STRUCTURE 1.58 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 834 - 101 - 2003 12639958
    4 - 796 - 101 - 2003 12639958
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Nervousbrain    
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminus of PSENEN is exposed to the cytoplasm, thus indicating that hydrophobic domains (HP1) does not traverse the lipid bilayer as a transmembrane domain, and first fourteen AAs of the HP1 are required for gamma-secretase activity
  • two transmembrane domains
  • C-terminal domain determining its function in the stabilization of presenilin fragments, that is lumenal
  • C-terminus , but the
    • HOMOLOGY
    interspecies homolog to murine Pen2
    Homologene
    FAMILY gamma-secretase protein complex
    CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • member of the gamma-secretase complex, playing a role, with PSEN1, NCSTN, APH1A, necessary and sufficient to reconstitute gamma-secretase activity
  • required for triggering PSEN1 endoproteolysis
  • required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex
  • concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity
  • rather than solely being a catalyst for gamma-secretase endoproteolysis, PSENEN may also stabilize the complex prior to PSEN1 endoproteolysis, allowing time for full assembly and proper trafficking
  • might likely be closely related to APP burden in aging nervous system (PMUID: 25736404)
  • plays a crucial role in substrate binding, a mechanism by which PSENEN contributes directly to the catalytic mechanism of gamma-secretase activity
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin APH1A, APH1B, PSENEN, that is responsible for the intramembranous cleavage of amyloid precursor protein (APP) and NOTCH
  • PSEN1 or PSEN2, nicastrin (NCSTN), anterior pharynx-defective 1 (APH1A), and PSENEN have been considered the minimal essential subunits required to form an active gamma-secretase complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • downregulation of RER1 leads to increased surface localization of PSENEN, whereas overexpression of RER1 stabilizes unassembled PSENEN
  • can interact with ferritin light chain (FTL), an important component of the iron storage protein ferritin
  • iron can increase gamma-secretase activity through promoting the level of FTL that interacts with and stabilizes PSENEN, providing a new molecular link between iron, PSENEN/gamma-secretase and A&
    • 946;PP generation in Alzheimer disease
  • extracellular domain of NCSTN directly binds PSENEN at the thin end
    • cell & other
    REGULATION
    Other TP53-dependent regulation of PSENEN expression by other members of the gamma-secretase complex, namely presenilins
    ASSOCIATED DISORDERS
    corresponding disease(s) ACNINV2
    Susceptibility to Alzheimer disease
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS