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FLASH GENE
Symbol BAK1 contributors: mct/npt/pgu/shn - updated : 26-05-2015
HGNC name BCL2-antagonist/killer 1
HGNC id 949
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three BCL2 homology domains from N terminal, BH1, BH2 and BH3 dimerization domain
  • a membrane anchoring segment
  • HOMOLOGY
    interspecies ortholog to Bak1, Mus musculus
    ortholog to Bak1, Rattus norvegicus
    ortholog to BAK1, Pan troglodytes
    Homologene
    FAMILY
  • multidomain proapoptotic family
  • Bcl-2 family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • resides in the outer mitochondrial membrane
  • constitutively located within the mitochondrial outer membrane
  • basic FUNCTION
  • binding the mitochondrial membrane permeability transition pore and promoting apoptosis by accelerating cytochrome c release
  • contributing with BAX to regulation of endoplasmic reticulum and mitochondria calcium, essential gateway for selected apoptotic signal
  • in association with BAX, 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)
  • is a required factor for long-chain ceramide production in response to pro-apoptotic stress
  • critical role for BAX and BAK1 in early T-cell development
  • with BAX, 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 (
  • BAX and BAK1 regulate necrosis, suggesting a connection between mitochondrial events that mediate apoptosis and necrosis
  • 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
  • forming a complex with BAX and with the cytosolic domain of IRE1alpha, that is essential for IRE1alpha activation
  • formation of BAK1 homo- or heterodimers is involved in the regulation of apoptosis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • anti-apoptotic Bcl-w and A1 (
  • myeloid cell leukemia-1, MCL-1 (
  • BCL2-associated X protein, BAX (
  • Heat shock protein 60, HSP60 (
  • alphaA- and alphaB-crystallins (
  • p53 (
  • mitofusin 2, Mfn2 (
  • BCL2 (context-dependent BCL2/BAK1 interactions regulate lymphoid cell apoptosis)
  • interacting with VDAC2
  • BCL2L11 and BBC3 can directly activate the proapoptotic proteins BAX and BAK1 to permeabilize mitochondria, leading to caspase activation and apoptosis
  • activates BAK1 to mitochondrial outer-membrane permeabilization (MOMP), which leads to apoptosis
  • BBC3 like BCL2L11, PMAIP1, is able to act as a direct BAK1 activator
  • 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
  • cell & other
    REGULATION
    activated by BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
    inhibited by VDAC2 (
    Other activation of both BAK1 and BAX is initiated by direct BH3-interaction but at distinct trigger sites
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in gastric and colorectal cancers (advanced stage)
    Susceptibility
  • to autoimmune rheumatic diseases (AIRDs) in women
  • to abdominal aortic aneurysms
  • to testicular germ cell tumor (TGCT)
  • to Sjögren syndrome
  • Variant & Polymorphism other
  • polymorphisms influencing the risk of acquiring AIRDs
  • association between genetic marker rs2227925 and TGCT risk
  • polymorphisms in BAK1 have been associated with Sjögren syndrome
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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
  • mice lacking Bak appear largely normal