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FLASH GENE
Symbol BCL2L11 contributors: mct/npt/pgu - updated : 05-03-2013
HGNC name BCL2-like 11 (apoptosis facilitator)
HGNC id 994
Location 2q13      Physical location : 111.878.490 - 111.926.022
Synonym name
  • BCL-2-related ovarian death agonist
  • BH3-only family member Bim
  • Synonym symbol(s) BIM, BOD, BIML, BIMEL, BAM, BIM-alpha6, BIM-beta6, BIM-beta7
    DNA
    TYPE functioning gene
    STRUCTURE 47.53 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure
  • transcription factor binding sites
  • eight endogenous E2F1-binding sites on the BCL2L11 promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    SEPT10 2q13 septin 10 FLJ21870 2q13 hypothetical protein FLJ21870 LOC391421 2 similar to Ribosome biogenesis protein BMS1 homolog LOC391422 2 similar to ribosomal protein L22 RANBP2L1 2q12.3 RAN binding protein 2-like 1 LOC339692 2q13 hypothetical protein LOC339692 GPAA1P1 2q12-q14 glycosylphosphatidylinositol anchor attachment 1 pseudogene 1 LOC391423 2 similar to zinc finger protein 499 LOC343938 2q13 similar to zinc finger protein BENE 2q13 BENE protein NPHP1 2q12-q13 nephronophthisis 1 (juvenile) LOC205251 2q13 hypothetical protein LOC205251 FLJ38359 2q13 hypothetical protein FLJ38359 LOC96626 2q14-q21 pinch-2 LOC391424 2 similar to ribosomal protein L22 LOC391425 2 similar to heparin-binding protein HBp15 BUB1 2q14 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) LOC339693 2q13 hypothetical LOC339693 FLJ11042 2q13 hypothetical protein FLJ11042 BCL2L11 2q13 BCL2-like 11 (apoptosis facilitator) LOC391426 2 similar to ENSANGP00000004103 ANAPC1 2q12.1 anaphase-promoting complex 1 (meiotic checkpoint regulator) MERTK 2q14.1 c-mer proto-oncogene tyrosine kinase FLJ14681 2q13 hypothetical protein FLJ14681 FLJ37440 2q13 hypothetical protein FLJ37440 LOC84524 2q13 zinc finger protein FLJ41410 2q13 FLJ41410 protein LOC389020 2 similar to RAN-binding protein 2-like 1 isoform 1; sperm membrane protein BS-63; RAN-binding protein 2-like 1 TTL 2q13 similar to RAN-binding protein 2-like 1 isoform 1; sperm membrane protein BS-63; RAN-binding protein 2-like 1 POLR1B 2q13 polymerase (RNA)1polypeptide B, 128kDa C2orf9 2q13 chromosome 2 open reading frame 9 SLC20A1 2q11-q14 solute carrier family 20 (phosphate transporter), member 1 FLJ40629 2q14.1 hypothetical protein FLJ40629 IL1A 2q13 interleukin 1, alpha IL1B 2q13 interleukin 1, beta IL1F7 2q12.1-q14.1 interleukin 1 family, member 7 (zeta) IL1F9 2q13 interleukin 1 family, member 9 IL1F6 2q12-q14.1 interleukin 1 family, member 6 (epsilon) IL1F8 2q12-q14.1 interleukin 1 family, member 8 (eta)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - - 36 . widely expressed in some carcinoma tissues and normal human tissues 2007 17717606
  • can trigger cell apoptosis by inducing cytochrome c release from mitochondria
  • 4 splicing 5106 22.2 198 integral mitochondrial membrane protein, the most prominent isoform up-regulated in prostate cancer cells 2012 22728771
  • the longest isoform
  • in BCL2L11 deficient T-cells, BIMEL and BIMS, promoted intrinsic cell death
  • regulated during mitosis by the AURKA and PPP2CA, (phosphorylated by AURKA early in mitosis and reversed by PPP2CA after mitotic exit)
  • 4 splicing 4919 - 138 - 2012 22728771
  • in frame compared to BIMEL
  • induces apoptosis more potent than isoform BIMEL
  • support acidification of lysosomes that later may associate with autophagic vesicles
  • over-expression of BIML restored acidic vesicles in BCL2L11 deficient T-cells
  • could be an adaptor for dynein to facilitate loading of lysosomes
  • novel role in lysosomal positioning that may be required for the formation of degradative autolysosomes
  • 4 - 728 - 112 - 1998 9430630
    5 - 5139 - 135 - 1998 9430630
    5 - 5231 - 169 - 1998 9430630
    5 - 5238 - 172 - 1998 9430630
    4 - 5127 - 140 - 1998 9430630
    3 - 5002 - 135 - 1998 9430630
    6 - 5051 - 109 - 1998 9430630
    5 - 4926 - 138 - 1998 9430630
    5 - 4947 - 80 - 1998 9430630
    4 - 4822 - 75 - 1998 9430630
    5 - 4952 - 75 - 1998 9430630
    6 - 5033 - 85 - 1998 9430630
    5 - 4961 - 79 - 1998 9430630
    5 - 4968 - 82 - 1998 9430630
    4 - 4836 - 108 - 2012 22728771
  • in BCL2L11 deficient T-cells, BIMEL and BIMS, promoted intrinsic cell death
  • 3 - 4732 - 45 - 1998 9430630
    6 - 958 - 98 - 1998 9430630
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Reproductivemale systemprostate   
    Urinarykidney    
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymhoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • short BH3 domain required for BCL-2 binding and cytotoxicity
  • a dynein binding domain (DBD), with a putative phosphorylation sites, playing a role for the anti-proapoptotic activity of GRB10
  • a hydrophobic C-terminus
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Bim
    homolog to murine Bcl2l11
    Homologene
    FAMILY
  • BH3-only family
  • Bcl-2 superfamily
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • localized to intracytoplasmic membranes
  • sequestered to the microtubule-associated dynein motor complex
  • primarily localized to mitochondrial and cytoskeleton-associated fractions (pMID: 23152504)
  • basic FUNCTION
  • regulator of cell death that operate at the mitochondrial membrane to control caspase activation,
  • involved in certain apoptotic responses and to prevent overproduction of hematopoietic cells
  • playing a role in neuronal and lymphocyte apoptosis
  • functionning as an essential initiator of the apoptosis in thymocyte-negative selection
  • involved in cytokine-dependent survival pathways
  • potent activator of apoptosis and, in neurons, induces the direct activation of BAX
  • with PMAIP1, establish a connection between FKHRL1 and mitochondria, and both BH3-only proteins are critically involved in FKHRL1-induced apoptosis in neuroblastoma
  • transcriptionally and/or post-translationally induced in response to diverse apoptotic stimuli, such as cytokine deprivation or deregulated calcium flux, in a broad range of hematopoeitic, epithelial, and neuronal cell types
  • mediates motoneuron loss in a model of amyotrophic lateral sclerosis
  • implicated in the regulation of cell death induction in multiple cell types and tissues in response to a large number of stimuli, including growth factor or cytokine deprivation, calcium flux, ligation of antigen receptors on T and B cells, glucocorticoid or loss of adhesion
  • playing an important role in eliminating activated T cells even when IL2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis
  • critical sensor and mediator in the mitochondrial-dependent apoptosis
  • with BAX are required for GNB2L1-mediated mitochondrial cell death
  • proapoptotic member of the BCL2 family and is primarily involved in the regulation of the intrinsic apoptotic pathway
  • essential for the initiation of several pathways that induce apoptosis in thymocytes, including cytokine withdrawal and calcium flux
  • essential for thymocyte apoptosis caused by strong TCR stimulation and critical for negative selection of autoreactive thymocytes
  • its expression may be responsible for the inherent sensitivity of the developing retinal vasculature to changes in oxygen levels, and promotes vessel obliteration in response to hyperoxia
  • apoptosis regulated by BCL2L11- and PMAIP1-driven loss of MCL1 is thus the final step in neutrophil differentiation, required for the termination of neutrophil function and neutrophil-dependent inflammation
  • for optimal tumor suppressive activity, must be able to interact with all and not just select pro-survival BCL2 family members
  • has a major role in hematopoietic homeostasis, particularly in the lymphocyte compartment, where it strongly affects immune function
  • inhibits autophagy by recruiting Beclin 1 to microtubules
  • in response to toxic stimuli, is released from its interaction with DYNLL1 and can induce apoptosis by inactivating anti-apoptotic BCL2 proteins and by activating BAX-BAK1
  • having a dual effects in inhibiting autophagy and promoting apoptosis and may have important roles in disease pathogenesis
  • plays a physiological role in promoting cell survival in addition to its well known function in apoptosis induction
  • BCL2L11 and BBC3 can directly activate the proapoptotic proteins BAX and BAK1 to permeabilize mitochondria, leading to caspase activation and apoptosis
  • BCL2L11 and BBC3 are the sentinels that interconnect kinase signaling networks and the mitochondrion-dependent apoptotic program, which offers therapeutic insights for designing novel cell death mechanism-based anticancer strategies
  • is required for cell death mediated by antimitotic agents
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text apoptotic activator
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimers with a number of antiapoptotic bcl-2 protein including MCL-1, BCL-2, BCL-XL, BFL-1 and BHRF1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to BCL2, BCL2L1/BCL-X(L), MCL1, BFL1, BHRF-1, LC8 cytoplasmic dynein light chain
  • 17beta-estradiol (E2) upregulates expression of antiapoptotic BCL2L2 and downregulates expression of proapoptotic BCL2L11 in an estrogen receptor (ER)-dependent manner
  • coordinated action of MCL1, IER3, and BCL2L11 controls cell death and survival (new regulatory circuit)
  • GRB10 interacted with the DBD (dynein binding domain) of BCl2L11 and inhibited apoptosis triggered by overexpression of DBD containing BCL2L11 isoforms
  • BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
  • PMAIP1 is strongly upregulated and became associated with both MCL1 and BCL2L11 during apoptosis induced by proteasome inhibition
  • PRKAR1A is an interacting partner of BCL2L11
  • TRIM2 binds to BCL2L11 when it is phosphorylated by p42/p44 MAPK
  • CCNB1 interacts with the BH3-only protein BCl2L11 and mediates its phosphorylation by CDK1 during mitosis
  • CDH2 engagement mediates neuronal cell survival by enhancing the MAP kinase pathway and down-regulating the pro-apoptotic protein BCL2L11
  • BBC3 cooperates with BCL2L11 to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease
  • interacts with BECN1, and this interaction is facilitated by DYNLL1 (BCL2L11 recruits BECN1 to microtubules by bridging BECN1 and DYNLL1, thereby inhibiting autophagy)
  • E2F1 binds to the BCL2L11 promoter at multiple sites
  • BBC3 like BCL2L11, PMAIP1, is able to act as a direct BAK1 activator
  • IL4 was able to inhibit BCL2L11 upregulation and prevent cell death
  • cell & other
  • intracytoplasmic membrane
  • REGULATION
    activated by by overexpression of TARDBP
    induced by the forkhead transcription factor FKHR-L1 and nerve growth factor (NGF)
    inhibited by MCL1
    Other regulated both in the transcript and post transcript process
    regulated by the ERK1/2 survival pathway (MAPK1 and MAPK3)
    hypoxic conditions inhibit anoikis and block expression of proapoptotic BCL2L11 and BMF in epithelial cells

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