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FLASH GENE
Symbol BAX contributors: mct/shn - updated : 26-05-2016
HGNC name BCL2-associated X protein
HGNC id 959
Location 19q13.33      Physical location : 49.458.116 - 49.465.054
Synonym name
  • apoptosis regulator BAX
  • determinant of chemo-sensitivity in tumor cell-lines
    • Synonym symbol(s) BCL2L4
    DNA
    TYPE functioning gene
    STRUCTURE 6.94 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • dissociation of CTBP1 from the BAX promoter increases BAX transcription and finally results in cell death
    • MAPPING cloned Y linked N status provisional
    Map cen - D19S902 - D19S596 - BAX - D19S879 - D19S604 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 888 21 192 - 2008 18590739
  • variant alpha
  • a distinct 3' coding region and 3' UTR when compared to variant beta
  • isoform alpha that has a shorter and different C terminus, as compared to isoform beta
  • isoform alpha is also known as isoform psi
    • 5 splicing 891 24 218 widely 2008 18590739
    longest isoform beta
    7 splicing 986 - - - 2008 18590739
  • transcript variant epsilon, non-coding RNA
  • 97 base insertion and producing a protein of 18kDa without BH2 and transmembrane domains
    • 6 splicing 849 19.5 179 - 2008 18590739
  • a distinct 3' coding region and 3'UTR compared to variant beta
  • isoform sigma is shorter and has a different C terminus
    • 5 splicing 741 15 143 - 2008 18590739
  • variant delta
  • lacking an in-frame segment within the coding region and containing a distinct C terminus as compared to variant beta
  • isoform delta as a shorter and different C terminus
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Endocrinepancreas    
    Lymphoid/Immunethymus    
    Nervousnerve   highly
    Reproductivemale systemprostate   
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningretinal pigment epithelium (RPE)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight alpha helices, with from the N terminal the BCL2 homology domains BH1, BH2, and BH3 dimerization domain, and with four signature hydrophobic AAs from the BH3 domain
  • a binding site for BH3 engagement that directly initiates BAX activation
  • a C terminal membrane anchoring segment
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Bax, Mus musculus
    ortholog to Bax, Rattus norvegicus
    intraspecies homolog to BCL2,extensively
    Homologene
    FAMILY
  • Bcl-2 family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • translocated and inserted into the mitochondrial membrane
  • redirected from the cytosol to mitochondria upon apoptotic induction
  • is recruited from the cytosol to the mitochondria, where it participates in cytochrome c release
  • BAX resides predominantly in the cytosol
  • BAX cytosol-to-mitochondria translocation is a central event of the intrinsic pathway of apoptosis
  • BAX localizes to the mitochondrial outer membrane via alternate mechanisms, either constitutively via an interaction with VDAC2 or after activation via interaction with BCL2 family proteins
    • basic FUNCTION
  • pro-apoptotic protein that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death
  • leading to cell death after heterodimerization with BCL2
  • modulating CDK2 activation during thymocyte apoptosis
  • contributing with BAK1 to regulation of endoplasmic reticulum and mitochondria calcium
  • essential gateway for selected apoptotic signal
  • maybe allowing survival of human cancer cells
  • in association with BAK1, functions at the ER membrane to activate inositol-requiring enzyme 1 alpha (IRE1alpha) and to provide a physical link between members of the core apoptotic pathway and the unfolded protein response (UPR)
  • mediates cytochrome c release and mitochondrial depolarization in lymphocytes, at least in part, via its interaction with mitochondrial KCNA3
  • apoptotic stimuli can facilitate the proapoptotic function of BAX in mitochondria through stabilization of MOAP1
  • with BCL2L11 are required for GNB2L1-mediated mitochondrial cell death
  • pro-apoptotic protein that mediates intrinsic cell-death signaling
  • critical role for BAX and BAK1 in early T-cell development
  • with BAK1, are required to prevent T-cell malignancy, and for normal T-cell differentiation, regulating early T-cell development at the stage of early T-lineage progenitor cells
  • regulates endoplasmic reticulum membrane permeability to luminal proteins during apoptosis (
  • participates in the regulation of mitochondrial fusion (
  • is the primary substrate responsible for the antiapoptotic effects of PARK2, providing mechanistic insight into at least a subset of the mitochondrial effects of PARK2
  • BAX and BAK1 regulate necrosis, suggesting a connection between mitochondrial events that mediate apoptosis and necrosis
  • BAX modulates necrosis through mechanisms distinct from apoptosis
  • functions of BCL2L2 and BAX are mimicked by other pro-survival and pro-apoptotic members, such as BCL2L1 and BAK, respectively
  • BAK1 and BAX are two proapoptotic members of the Bcl-2 protein family with overlapping, essential roles in the intrinsic apoptotic pathway
  • critical role for BAK1 and an ancillary role for BAX in safeguarding immunological tolerance and prevention of autoimmune disease
  • BAK1 and BAX are necessary for immunological tolerance of ubiquitous self-antigens
  • BAX and BAK1 mediate the permeabilization of the mitochondrial outer membrane during apoptosis
  • multidomain pro-apoptotic Bcl-2 family proteins BAK1 and BAX are believed to form large oligomeric pores in the mitochondrial outer membrane during apoptosis
  • analogous mechanism for activation and dimerization of BAK1 and BAX in response to certain BH3 peptides
  • oligomerized BAX and BAK1 trigger apoptosis by causing both the permeabilization of the mitochondrial outer membrane and activation OMA1
  • BAX and BAK1 can permeabilize the outer mitochondrial membrane and commit cells to apoptosis
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with BCL2
  • forming a complex with BAK1 and with the cytosolic domain of IRE1alpha, that is essential for IRE1alpha activation
  • pro-apoptotic pathway linking KRAS, RASSF1 and BAX that is specifically impaired in some human tumors
    • INTERACTION
    DNA
    RNA
    small molecule other,
  • association with mitochondria requires TOM22, a mitochondrial outer membrane protein
    • protein
  • B-cell CLL/lymphoma 2, BCL2 (
  • permeability transition pore complex, PTPC (
  • anti-apoptotic Bcl-w and A1 (
  • BFL-1 (
  • myeloid cell leukemia-1, MCL-1 (
  • modulator of apoptosis 1, MOAP1 (
  • SH3-domain GRB2-like endophilin B1, SH3GLB1 (
  • Bif-1 (
  • BCL2-antagonist/killer 1, BAK1 (
  • sigma and CDK1 (
  • Heat shock protein 60, HSP60 (
  • cytoplasmic protein 14-3-3 theta (
  • humanin, HN (
  • voltage-dependent anion channel 1, VDAC1 (
  • BH3 domains of Bid and PUMA (
  • NPM1
  • HIF1AN functions as a cytosol retention factor of BAX, blocking BAXtranslocation from cytosol to mitochondria in response to apoptotic stimuli
  • interacting with MCL1 and BCL2L1 (BAX BH3 domain complexing with the pro-survival proteins MCL1 and BCL2L1)
  • HRK plays a critical role in the survival of neuronal populations by regulating the multi-BH domain protein BAX
  • interaction with the cytosolic domain of TOMM22 helps BAX to acquire a conformation able to interact with the outer mitochondrial membrane
  • PARK2 prevented basal and apoptotic stress-induced translocation of BAX to the mitochondria
  • MUC1 associates with BAX in human cancer cells (binds directly to the BAX BH3 domain and thereby blocks BAX function in activating the mitochondrial death pathway)
  • BCL2L11 and BBC3 can directly activate the proapoptotic proteins BAX and BAK1 to permeabilize mitochondria, leading to caspase activation and apoptosis
  • ATXN3 promotes the interaction between BCL2L1 and BAX, but does not affect the ubiquitination and degradation of BCL2L1
  • BCL2L2 interacts with BAX and suppresses the CASP6 apoptotic cascade that fosters axonal degeneration
  • endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX, and colocalizes with BAX in a UV-inducible manner
  • antiapoptotic BCL2 family members do not directly inhibit components of the autophagic pathway but instead affect autophagy indirectly, owing to their inhibition of BAX and BAK1
  • protein interaction between DRAM1 and BAX and this interaction prolonged the half-life of BAX
  • MOAP1 is an integral partner to the tumor suppressor protein, (RASSF1), and functions to activate the BCL2 family pro-apoptotic protein BAX
  • BAX-binding protein enriched at the outer mitochondrial membrane (OMM)
  • bifunctional role of VDAC2 to target BAX specifically to the mitochondria and ensure BAX inhibition by retrotranslocation into the cytosol
    • cell & other
  • forming a permeability transition pore with BAK and increasing the release of cytochrome c
    • REGULATION
    activated by TP53 in apoptosis (transcriptional activator)
    BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
    induced by DRAM1 in a transcription-independent manner
    inhibited by presence of cholesterol in membranes (inhibits the pore-forming activity of BAX by reducing the ability of BAX to transition from a membrane-associated protein to a membrane-integral protein)
    IFNGR2
    Other degradated by the ubiquitin/proteasome dependent pathway
    activation of both BAK1 and BAX is initiated by direct BH3-interaction but at distinct trigger sites
    ASSOCIATED DISORDERS
    corresponding disease(s)
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    partial deletion exon 1(isoform BAXpsi) in glioblastoma multiforme (with increased survival)
    tumoral     --low  
    reduced expression is a poor prognosis factor in various carcinomas including breast cancer
    Susceptibility
  • breast cancer and glioblastoma multiforme
  • to osteomyelitis
    • Variant & Polymorphism other substitution of a nucleotide G-->A at position -248 in more frequent in patients with osteomyelitis and was associated with a longer lifespan of their peripheral blood neutrophils and lower BAX expression
    Candidate gene
    Marker
    Therapy target BAX activation site has important implications for the development of pharmacological agents to respectively activate or inhibit apoptosis in human diseases
    ANIMAL & CELL MODELS
  • Bax knockout mouse display lineage-specific aberrations in cell death, hyperplasia of thymocytes and B cells and ovaries contain unusual atretic follicles with excess granulosa cells (
  • mice deficient for Bax show only relatively mild abnormalities, including minor splenomegaly and male infertility
  • neonatal sympathetic neurons and facial motor neurons from Bax-deficient mice survived nerve growth factor deprivation and disconnection display remarkable soma atrophy and reduced elaboration of neurities (
  • mice nullizygous for both Bax and Atm showed additional reduction in ionizing radiation-induced apoptosis in the central nervous system (
  • bax(-/-)bak(-/-)mice died perinatally with fewer than 10% surviving into adulthood displaying multiple developmental defects, including persistence of interdigital webs, an imperforate vaginal canal, and accumulation of excess cells within both the central nervous and hematopoietic systems (
  • mouse embryonic fibroblasts deficient for BAX and BAK have a reduced resting concentration of calcium in the endoplasmic reticulum (
  • BAX- and BAK-deficient B cells display defective cell cycle progression to B cell receptor crosslinking and lipopolysaccharide (
  • in the T cell-specific BaxBak-deficient mice, early T-cell progenitors accumulate in the thymus, with relative depletion of more mature T cells