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FLASH GENE
Symbol AIFM1 contributors: mct/npt/pgu - updated : 12-01-2013
HGNC name apoptosis-inducing factor, mitochondrion-associated, 1
HGNC id 8768
Corresponding disease
COXPD6 combined oxidative phosphorylation deficiency 6
NAMSD axonal motor-sensory neuropathy, with deafness and mental retardation
Location Xq26.1      Physical location : 129.263.339 - 129.299.861
Synonym name
  • mitochondrial effector of apoptotic cell death
  • apoptosis inducing factor, mitochondrion
  • programmed cell death 8 (apoptosis-inducing factor)
  • striatal apoptosis-inducing factor
  • Synonym symbol(s) AIF, PDCD8, MGC111425, COXPD6
    EC.number 1.-.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 36.47 kb     17 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - DXS1059 - DXS1220 - HTR2C - COL4A6 - DXS8081 - DXS1001 - LAMP2 - UBE2A - DXS1212 - DXS1206 - AIFM1 - DXS1047 - qter
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 splicing 1925 28.3 261 - 2008 17967870
    16 splicing 2203 66 609 - 2008 17967870
    lacking exon 2
    8 splicing 1354 35 326 - 2008 17967870
  • lacking exons 2 to 10
  • encoding for the shortest product
  • 17 - 2418 35.25 324 - 2008 17967870
    16 - 2215 66.8 613 - 2008 17967870
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
    Endocrineadrenal gland   moderately
    Lymphoid/Immunethymus   moderately
    Skin/Tegumentskin   highly
    Urinarybladder   highly
     kidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal mitochondrial targeting sequence
  • C-terminal catalytic domain
  • conjugated FlavoP
    isoforms Precursor precursor protein is a 67 kDa polypeptide and after mitochondrial import and cleavage of a 54-amino-acid-long mitochondrial targeting sequence, the 62 kDa, mitochondrion-specific mature protein
    HOMOLOGY
    interspecies homolog to rattus Pdcd8 (92.65 pc)
    homolog to murine Aifm1 (92.32 pc)
    Homologene
    FAMILY
  • FAD-dependent oxidoreductase family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,chromatin/chromosome
    text
  • latent form stored in the mitochondrial intermembrane space, released into cytosol and nucleus in response to death stimuli
  • during apoptosis, released from the mitochondrial intermembrane space to the cytosol and to the nucleus
  • can be released from mitochondria and translocate to the nucleus where it participates in chromatin condensation and large-scale DNA fragmentation
  • after cleavage of the N-terminal mitochondrial targeting sequence, is posttranslationally inserted into the inner mitochondrial membrane, with the N terminus facing the matrix and the C-terminal catalytic domain exposed to the intermembrane space
  • imported from the endoplasmic reticulum to the mitochondria via mitochondria-associated membranes and transport vesicles
  • normally residing in the mitochondrial intermembrane space, AIF is released and translocated to the nucleus in response to proapoptotic stimuli
  • basic FUNCTION
  • releasing of apoptotic proteins cytochrome c and caspase 9
  • inhibiting protein synthesis by interacting with EIF3G
  • essential for the apoptotic effect of UBASH3A
  • required for specific cell death pathways, including lethal responses to excitotoxins such as N-methyl-D-aspartate and glutamate
  • key mediator of apoptosis, mitochondrial function, and cell survival
  • may act as a redox sensor with interrelated physiologic and apoptotic functions
  • essential for maintaining beta-cell mass and for oxidative stress response
  • may have a role in respiratory chain integrity and mtDNA maintenance, at least in some tissues
  • mitochondrial oxidoreductase that scavenges reactive oxygen species under normal conditions
  • BNIP3 and AIFM1 cooperate to induce apoptosis and cavitation during epithelial morphogenesis
  • mitochondrial flavoprotein that regulates cell metabolism and survival in many tissues
  • serves a lineage-specific nonredundant antiapoptotic role in the T cell lineage by regulating reactive oxygen species during thymic beta-selection
  • multifunctional protein that has diverse functions in both the mitochondria and the nucleus
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule cofactor,
  • FAD
  • protein
  • interaction between Scythe (BAT3) and the apoptogenic mitochondrial intermembrane protein AIFM1 (physically interacts with AIFM1 and regulates its stability)
  • new XIAP binding partner (role for XIAP in regulating cellular reactive oxygen species)
  • interacting with UBASH3A (enhances the apoptotic effect of AIFM1 by facilitating the interactions of AIFM1 with its apoptotic co-factors)
  • associates in the nucleus with histone H2AFX, and promotes chromatinolysis and caspase-independent programmed necrosis
  • STUB1 and USP2 show antagonistic functions in the control of AIFM1-mediated cell death, and implicate the role of the enzymes as a switch for cells to live or die under stresses that cause truncated AIFM1 release
  • NCOA1 interacts directly with AIFM1 in mitochondria and specifically inhibits caspase-independent and AIFM1-dependent apoptosis (PMId: 22371500)
  • regulated BNIP3 expression through mitochondrial production of reactive oxygen species and consequent HIF2A stabilization
  • BNIP3 and AIFM1 cooperate to induce apoptosis and cavitation during epithelial morphogenesis
  • AKIP1 localizes to the mitochondria and interacts with AIFM1
  • RAD23A is required for the nuclear translocation of AIFM1 during induction of cell death, and this process is energy dependent, but independent of karyopherins
  • cell & other
    REGULATION
    inhibited by BCL2 overexpression
    Other prolonged increase in intracellular Ca2+ concentration is required for AIFM1 processing and release during cell death
    ASSOCIATED DISORDERS
    corresponding disease(s) COXPD6 , NAMSD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in end-stage dilated cardiomyopathy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS