BCL2 (B-cell leukemia/lymphoma 2)

Identity

HGNC	BCL2
Location	18q21

DNA/RNA

	BCL2 (18q21) PAC 248E24 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are wellcome: contact M Rocchi
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

External links

	Nomenclature
HGNC	BCL2   990
Entrez_Gene	BCL2  596  B-cell CLL/lymphoma 2
	Cards
Atlas	BCL2ID49
GeneCards	BCL2
Ensembl	BCL2 [Search_View]   ENSG00000171791 [Gene_View]
Genatlas	BCL2
GeneLynx	BCL2
eGenome	BCL2
euGene	596
	Genomic and cartography
GoldenPath	BCL2  -  18q21   chr18:58941559-59137593 -  18q21.3   [Description]    (hg18-Mar_2006)
Ensembl	BCL2 - 18q21.3 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	BCL2
	Gene and transcription
Genbank	AF401211 [ ENTREZ ]
Genbank	AI401297 [ ENTREZ ]
Genbank	BC027258 [ ENTREZ ]
Genbank	DQ891470 [ ENTREZ ]
Genbank	DQ894654 [ ENTREZ ]
RefSeq	NM_000633 [ SRS ]    NM_000633 [ ENTREZ ]
RefSeq	NM_000657 [ SRS ]    NM_000657 [ ENTREZ ]
RefSeq	AC_000061 [ SRS ]    AC_000061 [ ENTREZ ]
RefSeq	AC_000150 [ SRS ]    AC_000150 [ ENTREZ ]
RefSeq	NC_000018 [ SRS ]    NC_000018 [ ENTREZ ]
RefSeq	NT_025028 [ SRS ]    NT_025028 [ ENTREZ ]
RefSeq	NW_001838469 [ SRS ]    NW_001838469 [ ENTREZ ]
RefSeq	NW_927106 [ SRS ]    NW_927106 [ ENTREZ ]
AceView	BCL2 AceView - NCBI
Unigene	Hs.150749 [ SRS ]    Hs.150749 [ NCBI ]     HS150749 [ spliceNest ]
Fast-db	5554 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P10415 [ SRS]    P10415 [ EXPASY ]     P10415 [ INTERPRO ]     P10415 [ UNIPROT ]
Prosite	PS50062 BCL2_FAMILY [ SRS ]    PS50062 BCL2_FAMILY [ Expasy ]
Prosite	PS01080 BH1 [ SRS ]    PS01080 BH1 [ Expasy ]
Prosite	PS01258 BH2 [ SRS ]    PS01258 BH2 [ Expasy ]
Prosite	PS01259 BH3 [ SRS ]    PS01259 BH3 [ Expasy ]
Prosite	PS01260 BH4_1 [ SRS ]    PS01260 BH4_1 [ Expasy ]
Prosite	PS50063 BH4_2 [ SRS ]    PS50063 BH4_2 [ Expasy ]
Interpro	IPR013278 Apop_reg_Bcl2 [ SRS ]    IPR013278 Apop_reg_Bcl2 [ EBI ]
Interpro	IPR002475 BCL2_apoptsis [ SRS ]    IPR002475 BCL2_apoptsis [ EBI ]
Interpro	IPR000712 Bcl2_BH [ SRS ]    IPR000712 Bcl2_BH [ EBI ]
Interpro	IPR003093 Bcl2_BH4 [ SRS ]    IPR003093 Bcl2_BH4 [ EBI ]
Interpro	IPR004725 Bcl2_reg [ SRS ]    IPR004725 Bcl2_reg [ EBI ]
CluSTr	P10415
Pfam	PF00452 Bcl-2 [ SRS ]    PF00452 Bcl-2 [ Sanger ]    pfam00452 [ NCBI-CDD ]
Pfam	PF02180 BH4 [ SRS ]    PF02180 BH4 [ Sanger ]    pfam02180 [ NCBI-CDD ]
Smart	SM00337 BCL [EMBL]
Smart	SM00265 BH4 [EMBL]
Blocks	P10415
PDB	1G5M [ SRS ]    1G5M [ PdbSum ],   1G5M [ IMB ]   1G5M [ RSDB ]
PDB	1GJH [ SRS ]    1GJH [ PdbSum ],   1GJH [ IMB ]   1GJH [ RSDB ]
PDB	1YSW [ SRS ]    1YSW [ PdbSum ],   1YSW [ IMB ]   1YSW [ RSDB ]
PDB	2O21 [ SRS ]    2O21 [ PdbSum ],   2O21 [ IMB ]   2O21 [ RSDB ]
PDB	2O22 [ SRS ]    2O22 [ PdbSum ],   2O22 [ IMB ]   2O22 [ RSDB ]
PDB	2O2F [ SRS ]    2O2F [ PdbSum ],   2O2F [ IMB ]   2O2F [ RSDB ]
HPRD	01045
	Protein Interaction databases
DIP	P10415
IntAct	P10415
	Polymorphism : SNP, mutations, diseases
OMIM	151430    [ map ]
GENECLINICS	151430
SNP	BCL2 [dbSNP-NCBI]
SNP	NM_000633 [SNP-NCI]
SNP	NM_000657 [SNP-NCI]
SNP	BCL2 [GeneSNPs - Utah]  BCL2] [HGBASE - SRS]
HAPMAP	BCL2 [HAPMAP]
COSMIC	BCL2 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	BCL2 [Translocation breakpoints In Cancer]
HGMD	BCL2
	General knowledge
Family Browser	BCL2 [UCSC Family Browser]
SOURCE	NM_000633
SOURCE	NM_000657
SMD	Hs.150749
SAGE	Hs.150749
GO	response to hypoxia [Amigo]  response to hypoxia
GO	release of cytochrome c from mitochondria [Amigo]  release of cytochrome c from mitochondria
GO	protease binding [Amigo]  protease binding
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	mitochondrion [Amigo]  mitochondrion
GO	mitochondrial outer membrane [Amigo]  mitochondrial outer membrane
GO	mitochondrial outer membrane [Amigo]  mitochondrial outer membrane
GO	mitochondrial outer membrane [Amigo]  mitochondrial outer membrane
GO	endoplasmic reticulum [Amigo]  endoplasmic reticulum
GO	endoplasmic reticulum membrane [Amigo]  endoplasmic reticulum membrane
GO	cytosol [Amigo]  cytosol
GO	anti-apoptosis [Amigo]  anti-apoptosis
GO	humoral immune response [Amigo]  humoral immune response
GO	female pregnancy [Amigo]  female pregnancy
GO	response to nutrient [Amigo]  response to nutrient
GO	cell death [Amigo]  cell death
GO	positive regulation of cell proliferation [Amigo]  positive regulation of cell proliferation
GO	activation of pro-apoptotic gene products [Amigo]  activation of pro-apoptotic gene products
GO	response to radiation [Amigo]  response to radiation
GO	response to heat [Amigo]  response to heat
GO	response to toxin [Amigo]  response to toxin
GO	response to inorganic substance [Amigo]  response to inorganic substance
GO	response to iron ion [Amigo]  response to iron ion
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
GO	response to caffeine [Amigo]  response to caffeine
GO	hair follicle morphogenesis [Amigo]  hair follicle morphogenesis
GO	nuclear membrane [Amigo]  nuclear membrane
GO	negative regulation of cellular pH reduction [Amigo]  negative regulation of cellular pH reduction
GO	response to cytokine stimulus [Amigo]  response to cytokine stimulus
GO	response to nicotine [Amigo]  response to nicotine
GO	B cell proliferation [Amigo]  B cell proliferation
GO	response to drug [Amigo]  response to drug
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	regulation of apoptosis [Amigo]  regulation of apoptosis
GO	response to peptide hormone stimulus [Amigo]  response to peptide hormone stimulus
GO	pigmentation [Amigo]  pigmentation
GO	regulation of protein homodimerization activity [Amigo]  regulation of protein homodimerization activity
GO	regulation of protein heterodimerization activity [Amigo]  regulation of protein heterodimerization activity
GO	negative regulation of neuron apoptosis [Amigo]  negative regulation of neuron apoptosis
GO	response to estrogen stimulus [Amigo]  response to estrogen stimulus
GO	regulation of viral genome replication [Amigo]  regulation of viral genome replication
GO	response to ethanol [Amigo]  response to ethanol
GO	regulation of mitochondrial membrane permeability [Amigo]  regulation of mitochondrial membrane permeability
GO	protein heterodimerization activity [Amigo]  protein heterodimerization activity
GO	BH3 domain binding [Amigo]  BH3 domain binding
GO	defense response to virus [Amigo]  defense response to virus
GO	regulation of mitochondrial membrane potential [Amigo]  regulation of mitochondrial membrane potential
GO	negative regulation of mitochondrial depolarization [Amigo]  negative regulation of mitochondrial depolarization
BIOCARTA	HIV-I Nef: negative effector of Fas and TNF    [Genes]
BIOCARTA	Regulation of BAD phosphorylation    [Genes]
BIOCARTA	Ceramide Signaling Pathway    [Genes]
BIOCARTA	Apoptotic Signaling in Response to DNA Damage    [Genes]
BIOCARTA	Induction of apoptosis through DR3 and DR4/5 Death Receptors    [Genes]
BIOCARTA	Stress Induction of HSP Regulation    [Genes]
BIOCARTA	IL-2 Receptor Beta Chain in T cell Activation    [Genes]
BIOCARTA	IL-7 Signal Transduction    [Genes]
BIOCARTA	Keratinocyte Differentiation    [Genes]
BIOCARTA	Melanocyte Development and Pigmentation    [Genes]
BIOCARTA	Role of Mitochondria in Apoptotic Signaling    [Genes]
BIOCARTA	p53 Signaling Pathway    [Genes]
BIOCARTA	Prion Pathway    [Genes]
BIOCARTA	Telomeres, Telomerase, Cellular Aging, and Immortality    [Genes]
KEGG	Neurodegenerative Disorders
KEGG	Apoptosis
KEGG	Focal adhesion
KEGG	Amyotrophic lateral sclerosis (ALS)
KEGG	Prion disease
KEGG	Colorectal cancer
PubGene	BCL2
TreeFam	BCL2
CTD	596 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	BCL2 (18q21) in normal cells (Bari)
Probe	BCL2 Related clones (RZPD - Berlin)
	PubMed
PubMed	499 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	05-1998	Jean-Loup Huret

Citation

This paper should be referenced as such :

Huret JL . BCL2 (B-cell leukemia/lymphoma 2). Atlas Genet Cytogenet Oncol Haematol. May 1998 . URL : http://AtlasGeneticsOncology.org/Genes/BCL2ID49.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:12:26 2008