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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
Location 6p21.31      Physical location : 33.540.323 - 33.548.070
Synonym name
  • cell death inhibitor 1
  • apoptosis regulator BAK
  • BCL2-like 7 protein
  • Bcl-2 homologous antagonist/killer
  • pro-apoptotic protein BAK
  • Synonym symbol(s) BAK, BCL2L7, CDN1, BAK-LIKE, MGC117255, MGC3887
    DNA
    TYPE functioning gene
    STRUCTURE 7.75 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D6S1666 - D6S1701 - BAK1 - D6S1560 - D6S1583 - qter
    Physical map
    VPS52 6p21.3 vacuolar protein sorting 52 (yeast) B3GALT4 6p21.3 UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, polypeptide 4 RPS18 6p21.3 ribosomal protein S18 C6orf11 6p21.3 chromosome 6 open reading frame 11 D6S2723E 6p21.3 DNA segment on chromosome 6 (unique, pseudogene) 2723 expressed sequence HKE2 6p21.3 HLA class II region expressed gene KE2 RAB2L 6p21.3 RAB2, member RAS oncogene family-like TAPBP 6p21.3 TAP binding protein (tapasin) ZNF297 6p21.3 zinc finger protein 297 DAXX 6p21.3 death-associated protein 6 LOC346177 6p21.31 similar to myosin:SUBUNIT=regulatory light chain LYPLA2P1 6p21.31 lysophospholipase II pseudogene 1 KIFC1 6p21.3 kinesin family member C1 PHF1 6p21.3 PHD finger protein 1 C6orf82 6pter-p21.31 chromosome 6 open reading frame 82 MGC23166 BAK1 6p21.3 BCL2-antagonist/killer 1 ITPR3 6p21 inositol 1,4,5-triphosphate receptor, type 3 C6orf125 6p21.31 chromosome 6 open reading frame 125 IHPK3 6p2131-p21.2 inositol hexaphosphate kinase 3
    RNA
    TRANSCRIPTS type
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2203 - 211 - 1998 9573342
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain    
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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