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BCL2 (B-cell leukemia/lymphoma 2)

Identity

HGNC (Hugo) BCL2
LocusID (NCBI) 596
Location 18q21.33
Location_base_pair Starts at 60790579 and ends at 60986613 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  BCL2 (18q21) PAC 248E24 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Description telomere to centromere orientation; 3 exons; exon 1 and the 3' part of exon 3 are non coding
Transcription 2 alternative transcripts (a and b); 5. 1 kb mRNA; coding sequence: CDS 1459...2178

Protein

Description 25 kDa; 205 amino acids (BCL2b) or 239 amino acids (BCL2a, which has, in addition, a hydrophobic tail for membrane anchorage; this tail seems necessary for anti apoptotic ability); contain homo/heterodimerization domains (BH) and NH domains.
Expression wide; in B and T cells in particular
Localisation mainly in the mitochondrial membrane; other membranes
Function antiapoptosis, through a possibly complex process; dimerization, especially with BAX; role of the BCL2 anti-apoptosis members in forming complexes with caspase-9 and APAF1 (homolog of the nematode CED-4), which prevent them to initiate the protease cascade (through caspase-3 cytochrome C dependent activation and) leading to apoptosis
Homology with Ced9 (nematode C. elegans); with other member of the BCL2 family: 1- apoptosis inhibitors BCLX, MCL1, and 2- apoptosis inducers BAX, BAD, BIK, ...

Implicated in

Entity t(14;18)(q32;q21)/B-cell malignancies --> IgH - BCL2
Disease B- cell NHL mainly; found in 80 to 90 % of follicular lymphomas, 30% of diffuse large cell lymphomas
Prognosis according to the cyto-pathologic subtype (small cleaved cell follicular lymphomas have a good prognosis; large cell lymphomas have a worse prognosis; the t(14;18) may have no prognostic significance)
Cytogenetics complex karyotypes are frequent with +7, del(6q), +12, + X,...
Hybrid/Mutated Gene 5' BCL2 translocated on chromosome 14 near JH (junctions genes of IgH) and C in 3'
Abnormal Protein no fusion protein, but promoter exchange; the immunoglobulin gene enhancer stimulates the expression of BCL2
Oncogenesis as BCL2 is an apoptosis inhibitor, cell death is delayed, and there is cell accumulation (more than real transformation)
  
Entity chronic lymphocytic leukaemia
Oncogenesis BCL2 is hypomethylated in the promotor region, and, therefore, overexpressed
  

Breakpoints

 

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029 t0812q24q22ID2057
t0814ID1050 8p11inMPDID1091 inv8p11q13ID1189 PrimarCutanALCLID2118

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004 blad5001

External links

Nomenclature
HGNC (Hugo)BCL2   990
Cards
AtlasBCL2ID49
Entrez_Gene (NCBI)BCL2  596  B-cell CLL/lymphoma 2
GeneCards (Weizmann)BCL2
Ensembl (Hinxton)ENSG00000171791 [Gene_View]  chr18:60790579-60986613 [Contig_View]  BCL2 [Vega]
ICGC DataPortalENSG00000171791
cBioPortalBCL2
AceView (NCBI)BCL2
Genatlas (Paris)BCL2
WikiGenes596
SOURCE (Princeton)NM_000633 NM_000657
Genomic and cartography
GoldenPath (UCSC)BCL2  -  18q21.33   chr18:60790579-60986613 -  18q21.3   [Description]    (hg19-Feb_2009)
EnsemblBCL2 - 18q21.3 [CytoView]
Mapping of homologs : NCBIBCL2 [Mapview]
OMIM151430   
Gene and transcription
Genbank (Entrez)AF401211 AI401297 BC027258 DQ891470 DQ894654
RefSeq transcript (Entrez)NM_000633 NM_000657
RefSeq genomic (Entrez)AC_000150 NC_000018 NC_018929 NG_009361 NT_010966 NW_001838469 NW_004929411
Consensus coding sequences : CCDS (NCBI)BCL2
Cluster EST : UnigeneHs.150749 [ NCBI ]
CGAP (NCI)Hs.150749
Alternative Splicing : Fast-db (Paris)GSHG0014341
Alternative Splicing GalleryENSG00000171791
Gene ExpressionBCL2 [ NCBI-GEO ]     BCL2 [ SEEK ]   BCL2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP10415 (Uniprot)
NextProtP10415  [Medical]
With graphics : InterProP10415
Splice isoforms : SwissVarP10415 (Swissvar)
Domaine pattern : Prosite (Expaxy)BCL2_FAMILY (PS50062)    BH1 (PS01080)    BH2 (PS01258)    BH3 (PS01259)    BH4_1 (PS01260)    BH4_2 (PS50063)   
Domains : Interpro (EBI)Apop_reg_Bcl2 [organisation]   Bcl2-like [organisation]   Bcl2/BclX [organisation]   Bcl2_BH1_motif_CS [organisation]   Bcl2_BH2_motif_CS [organisation]   Bcl2_BH3_motif_CS [organisation]   Bcl2_BH4 [organisation]   Bcl2_BH4_motif_CS [organisation]   Blc2_fam [organisation]  
Related proteins : CluSTrP10415
Domain families : Pfam (Sanger)Bcl-2 (PF00452)    BH4 (PF02180)   
Domain families : Pfam (NCBI)pfam00452    pfam02180   
Domain families : Smart (EMBL)BH4 (SM00265)  
DMDM Disease mutations596
Blocks (Seattle)P10415
PDB (SRS)1G5M    1GJH    1YSW    2O21    2O22    2O2F    2W3L    2XA0    4AQ3    4IEH    4LVT    4LXD    4MAN   
PDB (PDBSum)1G5M    1GJH    1YSW    2O21    2O22    2O2F    2W3L    2XA0    4AQ3    4IEH    4LVT    4LXD    4MAN   
PDB (IMB)1G5M    1GJH    1YSW    2O21    2O22    2O2F    2W3L    2XA0    4AQ3    4IEH    4LVT    4LXD    4MAN   
PDB (RSDB)1G5M    1GJH    1YSW    2O21    2O22    2O2F    2W3L    2XA0    4AQ3    4IEH    4LVT    4LXD    4MAN   
Human Protein AtlasENSG00000171791 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP10415
HPRD01045
IPIIPI00020961   IPI00217817   
Protein Interaction databases
DIP (DOE-UCLA)P10415
IntAct (EBI)P10415
FunCoupENSG00000171791
BioGRIDBCL2
InParanoidP10415
Interologous Interaction database P10415
IntegromeDBBCL2
STRING (EMBL)BCL2
Ontologies - Pathways
Ontology : AmiGOprotein polyubiquitination  response to acid  ossification  ovarian follicle development  metanephros development  branching involved in ureteric bud morphogenesis  behavioral fear response  B cell homeostasis  release of cytochrome c from mitochondria  release of cytochrome c from mitochondria  regulation of cell-matrix adhesion  protease binding  lymphoid progenitor cell differentiation  B cell lineage commitment  response to ischemia  renal system process  protein binding  nucleus  cytoplasm  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  endoplasmic reticulum  endoplasmic reticulum membrane  cytosol  protein dephosphorylation  melanin metabolic process  regulation of nitrogen utilization  apoptotic process  apoptotic process  humoral immune response  cellular response to DNA damage stimulus  actin filament organization  axonogenesis  female pregnancy  cell aging  transcription factor binding  male gonad development  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  intrinsic apoptotic signaling pathway in response to oxidative stress  response to radiation  response to toxic substance  post-embryonic development  response to iron ion  response to UV-B  response to gamma radiation  negative regulation of autophagy  negative regulation of calcium ion transport into cytosol  regulation of glycoprotein biosynthetic process  mesenchymal cell development  positive regulation of neuron maturation  positive regulation of smooth muscle cell migration  channel activity  membrane  cell growth  channel inhibitor activity  single organismal cell-cell adhesion  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  cochlear nucleus development  gland morphogenesis  regulation of transmembrane transporter activity  negative regulation of ossification  positive regulation of cell growth  negative regulation of cell growth  melanocyte differentiation  negative regulation of cell migration  positive regulation of B cell proliferation  hair follicle morphogenesis  axon regeneration  ubiquitin protein ligase binding  regulation of protein stability  nuclear membrane  endoplasmic reticulum calcium ion homeostasis  glomerulus development  negative regulation of cellular pH reduction  negative regulation of myeloid cell apoptotic process  T cell differentiation in thymus  positive regulation of peptidyl-serine phosphorylation  negative regulation of osteoblast proliferation  response to cytokine  response to nicotine  organ growth  nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway  positive regulation of multicellular organism growth  B cell proliferation  cellular response to glucose starvation  response to drug  response to drug  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  T cell homeostasis  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of catalytic activity  myelin sheath  CD8-positive, alpha-beta T cell lineage commitment  regulation of protein homodimerization activity  regulation of protein heterodimerization activity  negative regulation of neuron apoptotic process  sequence-specific DNA binding  ear development  regulation of viral genome replication  innate immune response  positive regulation of melanocyte differentiation  negative regulation of mitotic cell cycle  negative regulation of retinal cell programmed cell death  regulation of mitochondrial membrane permeability  pore complex  protein heterodimerization activity  focal adhesion assembly  spleen development  thymus development  digestive tract morphogenesis  developmental growth  oocyte development  positive regulation of skeletal muscle fiber development  pigment granule organization  homeostasis of number of cells within a tissue  B cell receptor signaling pathway  response to glucocorticoid  neuron apoptotic process  BH3 domain binding  defense response to virus  protein phosphatase 2A binding  regulation of mitochondrial membrane potential  negative regulation of mitochondrial depolarization  regulation of calcium ion transport  transmembrane transport  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  cellular response to organic substance  cellular response to hypoxia  reactive oxygen species metabolic process  extrinsic apoptotic signaling pathway in absence of ligand  intrinsic apoptotic signaling pathway  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  negative regulation of G1/S transition of mitotic cell cycle  negative regulation of anoikis  negative regulation of apoptotic signaling pathway  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  negative regulation of intrinsic apoptotic signaling pathway  positive regulation of intrinsic apoptotic signaling pathway  
Ontology : EGO-EBIprotein polyubiquitination  response to acid  ossification  ovarian follicle development  metanephros development  branching involved in ureteric bud morphogenesis  behavioral fear response  B cell homeostasis  release of cytochrome c from mitochondria  release of cytochrome c from mitochondria  regulation of cell-matrix adhesion  protease binding  lymphoid progenitor cell differentiation  B cell lineage commitment  response to ischemia  renal system process  protein binding  nucleus  cytoplasm  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  endoplasmic reticulum  endoplasmic reticulum membrane  cytosol  protein dephosphorylation  melanin metabolic process  regulation of nitrogen utilization  apoptotic process  apoptotic process  humoral immune response  cellular response to DNA damage stimulus  actin filament organization  axonogenesis  female pregnancy  cell aging  transcription factor binding  male gonad development  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  intrinsic apoptotic signaling pathway in response to oxidative stress  response to radiation  response to toxic substance  post-embryonic development  response to iron ion  response to UV-B  response to gamma radiation  negative regulation of autophagy  negative regulation of calcium ion transport into cytosol  regulation of glycoprotein biosynthetic process  mesenchymal cell development  positive regulation of neuron maturation  positive regulation of smooth muscle cell migration  channel activity  membrane  cell growth  channel inhibitor activity  single organismal cell-cell adhesion  peptidyl-serine phosphorylation  peptidyl-threonine phosphorylation  cochlear nucleus development  gland morphogenesis  regulation of transmembrane transporter activity  negative regulation of ossification  positive regulation of cell growth  negative regulation of cell growth  melanocyte differentiation  negative regulation of cell migration  positive regulation of B cell proliferation  hair follicle morphogenesis  axon regeneration  ubiquitin protein ligase binding  regulation of protein stability  nuclear membrane  endoplasmic reticulum calcium ion homeostasis  glomerulus development  negative regulation of cellular pH reduction  negative regulation of myeloid cell apoptotic process  T cell differentiation in thymus  positive regulation of peptidyl-serine phosphorylation  negative regulation of osteoblast proliferation  response to cytokine  response to nicotine  organ growth  nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway  positive regulation of multicellular organism growth  B cell proliferation  cellular response to glucose starvation  response to drug  response to drug  response to hydrogen peroxide  identical protein binding  protein homodimerization activity  T cell homeostasis  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of catalytic activity  myelin sheath  CD8-positive, alpha-beta T cell lineage commitment  regulation of protein homodimerization activity  regulation of protein heterodimerization activity  negative regulation of neuron apoptotic process  sequence-specific DNA binding  ear development  regulation of viral genome replication  innate immune response  positive regulation of melanocyte differentiation  negative regulation of mitotic cell cycle  negative regulation of retinal cell programmed cell death  regulation of mitochondrial membrane permeability  pore complex  protein heterodimerization activity  focal adhesion assembly  spleen development  thymus development  digestive tract morphogenesis  developmental growth  oocyte development  positive regulation of skeletal muscle fiber development  pigment granule organization  homeostasis of number of cells within a tissue  B cell receptor signaling pathway  response to glucocorticoid  neuron apoptotic process  BH3 domain binding  defense response to virus  protein phosphatase 2A binding  regulation of mitochondrial membrane potential  negative regulation of mitochondrial depolarization  regulation of calcium ion transport  transmembrane transport  intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress  cellular response to organic substance  cellular response to hypoxia  reactive oxygen species metabolic process  extrinsic apoptotic signaling pathway in absence of ligand  intrinsic apoptotic signaling pathway  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  negative regulation of G1/S transition of mitotic cell cycle  negative regulation of anoikis  negative regulation of apoptotic signaling pathway  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  negative regulation of intrinsic apoptotic signaling pathway  positive regulation of intrinsic apoptotic signaling pathway  
Pathways : BIOCARTACeramide Signaling Pathway [Genes]    IL-7 Signal Transduction [Genes]    Induction of apoptosis through DR3 and DR4/5 Death Receptors [Genes]    Melanocyte Development and Pigmentation [Genes]    Apoptotic Signaling in Response to DNA Damage [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    Keratinocyte Differentiation [Genes]    Telomeres, Telomerase, Cellular Aging, and Immortality [Genes]    Role of Mitochondria in Apoptotic Signaling [Genes]    Prion Pathway [Genes]    Regulation of BAD phosphorylation [Genes]    p53 Signaling Pathway [Genes]    Stress Induction of HSP Regulation [Genes]    HIV-I Nef: negative effector of Fas and TNF [Genes]   
Pathways : KEGGNF-kappa B signaling pathway    HIF-1 signaling pathway    Protein processing in endoplasmic reticulum    PI3K-Akt signaling pathway    Apoptosis    Adrenergic signaling in cardiomyocytes    Focal adhesion    Neurotrophin signaling pathway    Cholinergic synapse    Amyotrophic lateral sclerosis (ALS)    Toxoplasmosis    Tuberculosis    Hepatitis B    Epstein-Barr virus infection    Pathways in cancer    MicroRNAs in cancer    Colorectal cancer    Prostate cancer    Small cell lung cancer   
Protein Interaction DatabaseBCL2
Wikipedia pathwaysBCL2
Gene fusion - rearrangments
Rearrangement : TICdbBCL2 [18q21.33]  -  - [6q22.1]
Rearrangement : TICdbBCL2 [18q21.33]  -  - [4q12]
Rearrangement : TICdbAFF3 [2q11.2]  -  BCL2 [2p23.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)BCL2
snp3D : Map Gene to Disease596
SNP (GeneSNP Utah)BCL2
SNP : HGBaseBCL2
Genetic variants : HAPMAPBCL2
Exome VariantBCL2
1000_GenomesBCL2 
ICGC programENSG00000171791 
Cancer Gene: CensusBCL2 
Somatic Mutations in Cancer : COSMICBCL2 
CONAN: Copy Number AnalysisBCL2 
Mutations and Diseases : HGMDBCL2
Mutations and Diseases : intOGenBCL2
Genomic VariantsBCL2  BCL2 [DGVbeta]
dbVarBCL2
ClinVarBCL2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM151430   
MedgenBCL2
GENETestsBCL2
Disease Genetic AssociationBCL2
Huge Navigator BCL2 [HugePedia]  BCL2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneBCL2
Homology/Alignments : Family Browser (UCSC)BCL2
Phylogenetic Trees/Animal Genes : TreeFamBCL2
Chemical/Protein Interactions : CTD596
Chemical/Pharm GKB GenePA25302
Clinical trialBCL2
Cancer Resource (Charite)ENSG00000171791
Other databases
Probes
ProbeBCL2 (18q21) in normal cells (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineBCL2
iHOPBCL2
OncoSearchBCL2

Bibliography

Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18.
Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW, Epstein AL, Korsmeyer SJ
Cell. 1985 ; 41 (3) : 899-906.
PMID 3924412
 
Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18.
Cleary ML, Sklar J
Proceedings of the National Academy of Sciences of the United States of America. 1985 ; 82 (21) : 7439-7443.
PMID 2865728
 
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death.
Oltvai ZN, Milliman CL, Korsmeyer SJ
Cell. 1993 ; 74 (4) : 609-619.
PMID 8358790
 
Structure, function, and regulation of human cAMP-dependent protein kinases.
Taskˆ©n K, Skˆ€lhegg BS, Taskˆ©n KA, Solberg R, Knutsen HK, Levy FO, Sandberg M, Orstavik S, Larsen T, Johansen AK, Vang T, Schrader HP, Reinton NT, Torgersen KM, Hansson V, Jahnsen T
Advances in second messenger and phosphoprotein research. 1997 ; 31 : 191-204.
PMID 9344252
 
Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation.
Hu Y, Benedict MA, Wu D, Inohara N, Nˆ†ˆ±ez G
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (8) : 4386-4391.
PMID 9539746
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written05-1998Jean-Loup Huret

Citation

This paper should be referenced as such :
Huret, JL
BCL2 (B-cell leukemia/lymphoma 2)
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):113-114.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/BCL2ID49.html

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indexed on : Sat Oct 4 13:00:28 CEST 2014

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