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FLASH GENE
Symbol PSENEN contributors: mct - updated : 14-03-2018
HGNC name presenilin enhancer gamma-secretase subunit
HGNC id 30100
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