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FLASH GENE
Symbol BIK contributors: mct/pgu - updated : 10-06-2020
HGNC name BCL2-interacting killer (apoptosis-inducing)
HGNC id 1051
Location 22q13.2      Physical location : 43.506.756 - 43.525.717
Synonym name
  • apoptosis inducer NBK
  • natural born killer
  • Synonym symbol(s) NBK, BP4, BBC1, BIP1
    DNA
    TYPE functioning gene
    STRUCTURE 18.96 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D22S283 - ADSL - BIK - D22S272 - qter
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 963 - 160 - 2006 17047080
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon lowly
     stomach   lowly
    Lymphoid/Immunelymph node   moderately
     tonsils   highly
    Reproductivemale systemprostate  lowly
    Urinarykidney   lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymhoid/Immunelymphocyte
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • BH3 containing protein, as BAX and BAK1
  • HOMOLOGY
    Homologene
    FAMILY
  • BCL2 family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nuclear envelope
    text
  • colocalizing with cytoplasmic and nuclear membranes
  • intracytoplasmic membrane
  • single-pass membrane protein
  • predominantly localized to the endoplasmic reticulum (predominantly to the outer membrane of the endoplasmic reticulum) where it regulates BAX/BAK-dependent release of Ca2+ from the endoplasmic reticulum stores and cooperates with other BH3-only proteins such as PMAIP1 to cause rapid release of cytochrome c from mitochondria and activate apoptosis
  • basic FUNCTION
  • acting as a likely target for antiapoptotic proteins
  • inducing apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria and remodeling the mitochondrial cristae
  • also inducing non-apoptotic cell death
  • involved in the selection of mature B cells
  • critical effector in apoptosis induced by toxins, cytokines virus infections
  • proapoptotic tumor suppressor
  • plays a critical role in promotion of anti-estrogen-induced cell death in breast cancer cells
  • has a role in both, apoptosis induction and sensitivity to oxidative stress in myeloma cells
  • inactivate BCL2 through complex formation
  • key mediator of estrogen-starvation and anti-estrogen induced apoptosis
  • stronger inducer of apoptosis than PMAIP1, and when expressed simultaneously, a combinative effect was observed
  • initiator of mitochondrial apoptosis, and its expression is induced by proapoptotic signals, including DNA damage
  • TUT1-control of BIK expression and apoptosis is regulated by nuclear PIP5K1A and PRKCD signaling
  • can be a critical mediator of melanoma cell fate determination in response to MAPK pathway inhibition
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • BIK not only forms complex with BCL2, but it also forms complex with HSPA5
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • the cellular survival-promoting proteins BCL2 as well as with adenovirus E1b-19kDa protein
  • participating in the cleavage of BIK, a proapoptotic member of the BCL2 family
  • interaction of HSPA5 with BIK does not require its BH3 domain, which has been implicated in all previous BIK protein interactions
  • interacting with HSPA5 (HSPA5 confers resistance to apoptosis induced by BIK and PMAIP)
  • CUL5-ASB11 is the E3 ligase targeting BIK for ubiquitination and degradation
  • different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive
  • cell & other
    REGULATION
    activated by
  • TP53
  • several anti-cancer drugs
    induced by
  • strongly induced in cancer cells treated with chemotherapeutic agents
  • E2F in cancer cells
  • Other is regulated by the ubiquitin-proteasome system
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    mutated in B-cell lymphomas
    tumoral   deletion    
    chromosomal deletions encompassing BIK locus or epigenetic silencing in cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic or therapeutic marker in breast cancer patients according to the estrogen receptor alpha expression
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    prominent target for anti-cancers drugs that inhibit proteasomal functions
    cancer  
    therapeutic molecule in gene therapy-based approaches to treat difficult cancers
    cancer  
    blocking BIK degradation has the potential to be used as an anti-cancer strategy
    ANIMAL & CELL MODELS