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FLASH GENE
Symbol BCL2 contributors: mct/shn - updated : 21-07-2012
HGNC name B-cell CLL/lymphoma 2
HGNC id 990
Corresponding disease
BCL2 non Hodgkin follicular lymphoma of B-cell type
CLL2 chronic lymphocytic leukemia
Location 18q21.33      Physical location : 60.790.578 - 60.986.613
Synonym name apoptosis regulator Bcl-2
Synonym symbol(s) Bcl-2
DNA
TYPE functioning gene
STRUCTURE 196.04 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (CAAT box) (TATA box)
Binding site
text structure
  • a promoter region named M, between P1 and P2
  • P1 promoter is the main driving force for transcribing the bcl2 gene and P1 activity is modulated by M and P2 in a TP53-dependent and -independent manner
  • 5prime upstream region of BCL2 contains a number of elements that control its expression
  • a highly conserved 25-nucleotide G-rich sequence (BCL2Q), with potential to fold into a RNA G-quadruplex structure, located 42 nucleotides upstream of the translation start site
  • ATF5 binds to an ATF5-specific regulatory element that is downstream of and adjacent to the negative regulatory element in the BCL2 P2 promoter, stimulating BCL2 expression
  • a 279-bp major breakpoint region (mbr) within the 3prime-untranslated region is a binding site of special AT-rich sequence binding protein 1 (SATB1) that is well known to participate in the long-range regulation of gene transcription
  • MAPPING cloned Y linked N status confirmed
    Map cen - D18S1147 - D18S60 - BCL2 BCL2 - D18S68 - D18S55 - qter
    Physical map
    PIGN 18q21.32 phosphatidylinositol glycan, class N KIAA1468 18q21.33 KIAA1468 TNFRSF11A 18q21.3-q22.1 tumor necrosis factor receptor superfamily, member 11a, activator of NFKB LOC390861 18 similar to FKSG30 ZCCHC2 18q21.32 zinc finger, CCHC domain containing 2 PLEKHE1 18q21.32 pleckstrin homology domain containing, family E (with leucine rich repeats) member 1 BCL2 18q21.33 B-cell CLL/lymphoma 2 FVT1 18q21 follicular lymphoma variant translocation 1 VPS4B 18q21.32-q21.33 vacuolar protein sorting 4B (yeast) SERPINB5 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 5 SERPINB12 18q21 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 12 SERPINB13 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 13 SERPINB4 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 4 SERPINB3 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 3 SERPINB11 18q21.33 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 11 SERPINB7 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 7 SERPINB2 18q21.32-q21.33 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2 SERPINB10 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 10 LOC284293 18q22.1 similar to Placental thrombin inhibitor (Cytoplasmic antiproteinase) (CAP) (Protease inhibitor 6) (PI-6) SERPINB8 18q21.3 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 8 MGC39571 18q22.1 hypothetical protein MGC39571
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 6492 26.2 239 - 2008 18334006
  • Bcl-2 alpha isoform
  • including exon 1 and 2
  • 2 splicing 1207 25 205 - 2008 18334006
    Bcl-2 beta isoform
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid    
    Nervousnerve    
    Reproductivefemale systemovary   
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines pro B lymphocytes cell line
    fluid/secretion blood, lymph
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four BH domains (BH1, BH2, BH3, BH4), and the BH1 and BH2 domains are involved in pore formation; the BH3 and BH4 domains are the toxic and pro-survival domains, respectively
  • transmembrane (TM) domain required for inhibition of BRCA1 foci assembly
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Bcl2, Mus musculus
    ortholog to Bcl2, Rattus norvegicus
    ortholog to BCL2, Pan troglodytes
    Homologene
    FAMILY
  • anti-apoptotic Bcl2 family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • predominantly found on the outer mitochondrial membrane and endoplasmic reticulum membranes
  • BCL2 and BRCA1 colocalized to mitochondria and endoplasmic reticulum in a process requiring the TM domain of BCL2
  • basic FUNCTION
  • blocks the apoptotic death of cells such as lymphocytes
  • can target RAF1 to the mitochondria
  • inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to APAF1
  • prediction of prognosis in diffuse large B-cell lymphoma
  • has antiautophagy function (inhibiting the formation of BECN1/PI3K complex) that may help to maintain autophagy at levels compatible with cell survival
  • prototypic anti-apoptotic protein involved in the regulation of apoptosis
  • functions as an activator of the AKT1 signaling pathway in pancreatic cancer
  • plays critical roles in the control of apoptosis
  • essential mediator for the cancer-specific cell survival function of ATF5 in glioblastoma and breast cancer cells
  • playing an essential role in mediating the cell type-dependent prosurvival function of ATF5
  • in addition to its canonical anti-apoptotic role, negatively impacts genome stability
  • role of BCL2 and its pro-survival relatives in tumourigenesis and cancer therapy
  • crucial regulator of exercise- (and starvation)-induced autophagy, and autophagy induction may contribute to the beneficial metabolic effects of exercise
  • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    text cell cycle regulation, negative control of proliferation, humoral immune response
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
  • PO4
  • protein
  • carnitine palmitoyltransferase I, CPT1 (
  • calcineurin (
  • harakiri, HRK (
  • p28 Bap31 (
  • BNIP1 variants (
  • BCL2-associated transcription factor 1, BCLAF1 (
  • paxillin, PXN (
  • BCL2/adenovirus E1B 19kDa interacting protein 3-like, BNIP3L (
  • RAS (
  • Presenilin 1, PS1 (
  • BCL2/adenovirus E1B 19kDa interacting protein 3, BNIP3 (
  • modulator of apoptosis 1, MOAP1 (
  • PP1alpha and Bad (
  • poly (ADP-ribose) polymerase, PARP (
  • cis-trans peptidyl prolyl isomerase, Pin1 (
  • integral membrane protein 2B, ITM2B (
  • FK506 binding protein 8, 38kDa, FKBP38 (
  • binding and inactivating APAF1
  • BAX (
  • RAF1, TP53BP2
  • BCL2/adenovirus E1B 19kD interacting protein like 2, BNIPL-2 (
  • orphan nuclear receptor Nur77 (
  • BCL2-associated agonist of cell death, BAD (
  • NALP1, reducing caspase-1 activation and interleukin-1beta, IL-1beta (
  • interaction between HNRNPL and CA repeats of BCL2 mRNA participates in destabilizing BCL2 mRNA
  • SOD1, through its N-terminal portion between the BH4 and the loop domain
  • beclin 1, autophagy related, BECN1 (
  • BCL2 anti-apoptotic and autophagy inhibitory protein, is a substrate for parkin (PARK2)
  • BCL2 is a downstream target of ATF5 that mediates the prosurvival function of ATF5 in C6 glioma cells (
  • LGALS7 is a new mitochondrial BCL2 interacting partner
  • a dynamic interaction exists between AMBRA1 and BC-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis)
  • during early apoptosis, SATB1 was a key regulator of BCL2 expression
  • BRCA1, which plays an essential role in homologous recombination (HR), is a target for BCL2 in the repression of HR
  • ATG12 directly regulates the apoptotic pathway by binding and inactivating prosurvival BCL2 family members, including BCL2 and MCL1
  • role of NFE2L2 in control of BCL2 expression and apoptotic cell death with implications in antioxidant protection, survival of cancer cells, and drug resistance
  • induces autophagy by disrupting the association between BCL2 and BECN1
  • BCL2 proteins suppressed mitophagy through inhibition of PARK2 translocation to depolarized mitochondria
  • cell & other
    REGULATION
    activated by nerve growth factor
    inhibited by (-)-gossypol (
    Other expression increased by IGF1 associated with protection of neuroblastoma cells from apoptosis
    expression increased by VEGF with decreased apoptosis in neuroblastoma cells
    mediated by the p42/p44 MAPK cascade
    phosphorylation mediated by microtubule-damaging drugs through JNK- and cAMP-dependent protein kinases
    proteolytically cleaved by caspase during apoptosis
    regulated by FKBP8 (a key player in regulating the function of BCL2 by antagonizing caspase-dependent degradation through the direct interaction with the flexible loop domain of BCL2, which contains the caspase cleavage site)
    regulated by protein phosphatase 2A, PP2A (
    ASSOCIATED DISORDERS
    corresponding disease(s) BCL2 , CLL2
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in uterus endometrial carcinoma and in small cell lung carcinoma with poor prognosis
    tumoral   translocation    
    t(14;18)(q32;q21) in follicular lymphoma
    tumoral        
    in oral squamous cell carcinoma with poor prognosis
    tumoral     --other  
    BCL6-mediated suppression of BCL2 can be altered in DLBCL (diffuse large B cell lymphoma ) by different mechanism), including chromosomal translocations of the BCL2 gene, somatic mutations in the BCL2 promoter region, and deregulated expression of PIAS2
    tumoral     --over  
    in pancreatic cancer confers resistance to the apoptotic effect of chemo- and radiotherapy
    constitutional     --low  
    in the autistic brain
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC
  • combination modalities targeting the multiple oncogenic activities of BCL6 and the anti-apoptotic function of BCL2 may represent a rational approach for the treatment of a subset of DLBCL
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathycongenital
    for therapy of MDC1A, congenital muscular dystrophy, merosin negative (ameliorating disease by inhibition of the apoptosis)
    neuromuscularlaterale amyotrophy sclerosis 
    specific target and active partner in mutant SOD1 mitochondrial toxicity suggesting new therapeutic strategies to inhibit the formation of the toxic mutant SOD1/BCL2 complex and to prevent mitochondrial damage in ALS1
    ANIMAL & CELL MODELS