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FLASH GENE
Symbol CASP9 contributors: mct/npt/pgu - updated : 18-05-2014
HGNC name caspase 9, apoptosis-related cysteine peptidase
HGNC id 1511
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
conjugated ubiquitinated
mono polymer heteromer , dimer
isoforms Precursor producing two subunits, large and small that dimerize
HOMOLOGY
interspecies ortholog to murine Casp9
ortholog to rattus casp9
Homologene
FAMILY
  • caspase family of cysteinyl-aspartate specific proteases
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text procaspase 9 stored in mitochondrial intermembrane space released in the cytosol after appropriate apoptotic stimuli
    basic FUNCTION
  • containing aspartate specific protease
  • involved in the activation cascade of caspases responsible for apoptosis execution
  • during apoptosis, the initiator caspase 9 is activated at the apoptosome after which it activates the executioner caspases 3 and 7 by proteolysis
  • initial caspase in the mitochondrial apoptotic cascade
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • two subunits, large and small that dimerize
  • ATG7·CASP9 complex performs a dual function of linking CASP9 to the autophagic process while keeping in check its apoptotic activity
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cleaving and activating CASP3 and initiating apoptotic cascade after its activation
  • oxidative modification of CASP9 facilitates its activation via disulfide-mediated interaction with APAF1
  • BIRC2 cooperatively interacts with oligomerized processed CASP9 in the apoptosome and blocks procaspase-3 activation
  • interacting with MAPK8 (MAPK8 activation was essential for CASP9 activation and nuclear translocation of cytochrome c) . CASP4 directly activates CASP9 by the processing of procaspase-9 at Asp-315 in ER stress-induced neuronal apoptosis
  • after activation by CASP9, CASP3 inhibits ROS production and is required for efficient execution of apoptosis, while effector CASP7 is required for apoptotic cell detachment
  • CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
    • cell & other
    REGULATION
    activated by APAF1 cytochrome C multimeric complex
    induced by staurosporine that can induce caspase-9 activation and apoptosis independently of the apoptosome
    cellular oxidative state facilitates CASP9 activation
    inhibited by BIRC2, BIRC3, BIRC4 (XIAP)
    Phosphorylated by DYRK1A that phosphorylates CASP9 on threonine residue 125, and this phosphorylation event is crucial to protect retina cells from apoptotic cell death
    Other polyubiquitinated by BIRC4, while procaspase-9 was not
    PDCD6IP is a crucial mediator of Ca(2+) induced CASP9 activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in neurons of Alzheimer disease (before cleavage of tau and formation of neurofibrillary tangles)
    Susceptibility to modification of survival in non-small-cell lung cancer (NSCLC)
    Variant & Polymorphism other
  • rs4645981 polymorphisms may affect survival in early-stage NSCLC
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS