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Symbol APAF1 contributors: mct/npt/pgu - updated : 05-06-2015
HGNC name apoptotic peptidase activating factor 1
HGNC id 576
Location 12q23      Physical location : 99.039.077 - 99.129.204
Synonym name
  • apoptotic protease activating factor
  • C.elegans cell death 4 homolog
  • cytoplasmic scaffolding apoptotic protease activating factor
  • Synonym symbol(s) KIAA0413, CED4, APAF, APAF-1, DKFZp781B1145
    TYPE functioning gene
    STRUCTURE 90.13 kb     27 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D12S327 - D12S1657 - APAF1 - D12S393 - D12S1706 - D12S346 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    26 - 7042 135 1194 - 2007 17348858
    27 - 7171 140 1237 - 2007 17348858
    27 - 7204 141 1248 - 2007 17348858
    26 - 7075 137 1205 - 2007 17348858
    8 - 4559 37 338 - 2007 17348858
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Endocrineparathyroid   highly
    Hearing/Equilibriumear   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    SystemCellPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
  • a N terminal CARD (caspase recruitment domain), CARD-NOD domain, directly interacting with the NOD domains of NAIP
  • twelve WD repeats (an insertion of 11 repeats between the CARD
  • ATPase domains and another 43AA insertion creating an additional WD-40 repeat)
  • a poly Ser domain (95-98 AA) and a NB-ARC domain (AA 93 to 403)
  • a CED4 domain involved in interaction with UTP6 , and that directly binds to the central domain of NUP107 in an ATR-regulated, phosphorylation-dependent manner
  • a central nucleotide-binding oligomerization domain
  • multiple WD40 domain repeats at the C-terminus that bind to Cytochrome C
  • mono polymer heteromer
    interspecies ortholog to C.elegans CED3 (NH2 terminal) and CED4
  • WD (TRP-ASP) repeats (mediating protein protein interactions) family
  • CATEGORY adaptor , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • functions as an adaptor in an 700-kDa multiprotein complex (named the apoptosome) to mediate the activation of caspase-9
  • activating apoptosis caspase 9 and APF1 complex apoptosome in presence of cytopchrome C and ATP-leading to activation of caspase 3 and so to apoptosis
  • induced NF kappaB and NICK signaling molecules
  • hemoglobin scavenger receptor
  • might have a hitherto unsuspected role in the maintenance of genomic stability and cell cycle arrest, independent from its function in the apoptosis machinery
  • caspase-activating complex, APAF1 plays a central role in the mitochondrial caspase activation pathway of apoptosis
  • essential factor for cytochrome c-driven caspase activation during mitochondrial apoptosis but has also an apoptosis-unrelated function
  • implication in DNA damage-induced cell-cycle arrest (exerts two distinct, phylogenetically conserved roles in response to mitochondrial membrane permeabilization and DNA damage)
  • involvement in melanoma progression and chemoresistance
  • playing a necessary role for the cleavage or activation of all procaspases and the promotion of mitochondrial apoptotic events induced by genotoxic drugs
  • essential component of the apoptosome, the molecular complex assembled in response to mitochondrial cytochrome c release that promotes caspase activation
  • role in the maintenance of genomic stability, independently from its function in the cell death machinery
  • does not require energy from nucleotide hydrolysis to eventually form the apoptosome
  • key regulator gene of apoptosis, located downstream from TP53
  • having a non-apoptosis-related role in the pathology of protein-aggregation-dependent neurodegenerative diseases such as Huntington disease
  • required for minocycline-dependent inhibition of cell death
  • might potentially serve as a direct or indirect sensor or modulator of ER/mitochondria metabolic condition
  • relays the death signal in the mitochondrial pathway of apoptosis
  • main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway
  • acts by regulating the recruitment of UTP6, with which it interacts, to the centrosome
  • might also be considered a pro-survival molecule, whose absence impairs cell performance and causes a higher responsiveness to stressful conditions
  • involved in the DNA damage response through cell-cycle arrest induced by genotoxic stress
  • crucial role of APAF1 nuclear relocalization in mediating cell-cycle arrest induced by genotoxic stress
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development , immunity/defense
    text neurogenesis
    a component
  • forming a large multimeric complex the apoptosome, dATP dependent with cytochrome C1 (CYC1) and the initiator of apoptosis caspase 9, that activates caspase 3
    small molecule
  • caspase 9 (by their NH2 terminal CED3 homologous domain) in the presence of cytochrome C1 and ATP
  • mediating the endocytosis of the hemoglobin-haptoglobin complex
  • interacting with RIPK2 and potentially inducing NF-Kappa B activity through TRAF6 and NIKs (NF-Kappa B inducing kinase)
  • target of TP53 in DNA damage-induced apoptosis
  • during apoptosis, binds cytochrome c released from mitochondria to the cytosol
  • UACA is a APAF1-binding proapoptotic protein involved in apoptosome-mediated apoptosis
  • oxidative modification of CASP9 facilitates its activation via disulfide-mediated interaction with APAF1
  • NAIP interacts with the NOD domain of APAF1, through its NOD domain
  • in addition to APAF1 or apoptosome formation, DIABLO is also essential for MTCH1-induced apoptosis
  • APAF1 associates with the nucleoporin NUP107 and this association is necessary for APAF1 nuclear import
  • CIAO2A bind APAF1 and enhances the induction of mitochondrial apoptosis
  • cell & other
  • cytochrome C
    inhibited by not inhibited by binding to BCL2
    repressed by minocycline, which inhibits intrinsic (mitochondrial-mediated) but not extrinsic-mediated apoptosis activation through an inhibitory effect on APAF1 activity
    Other acute phase regulated
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    associated with tumour progression and adverse prognosis in colorectal cancer
    tumoral     --over  
    is related to an undifferentiated state in the testicular germ cell tumor pathway
    constitutional       loss of function
    results in an accumulation of neural progenitor cells (NPCs) in the developing central nervous system and thus, in perinatal lethality
    constitutional     --low  
    APAF1-deficient cells are less prone to developing aggregates than are wild-type cells, thereby supporting the involvement of APAF1 in a mammalian model of polyQ-related diseases
    Variant & Polymorphism
    Candidate gene
    Therapy target
    neurologyneurodegenerativehuntington chorea
    minocycline inhibits cell death and decreases mutant Huntingtin aggregation by targeting APAF1
  • murine Apaf1 null die at E16.5 day with craniofacial malformation, brain overgrowth, lens and retina alteration but persistence of interdigital webs and reduced apoptosis in fibroblasts
  • a Drosophila model of Huntington disease shows that inactivation of the dark gene (Drosophila Apaf-1 related killer) suppresses the formation of polyQ aggregates and diminishes the associated pathogenesis