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NameApoptosis regulator Bcl-2
SynonymsNot Available
Gene NameBCL2
Amino acid sequence
>lcl|BSEQ0000491|Apoptosis regulator Bcl-2
Number of residues239
Molecular Weight26265.66
Theoretical pI7.32
GO Classification
  • sequence-specific DNA binding
  • protease binding
  • channel inhibitor activity
  • protein heterodimerization activity
  • protein homodimerization activity
  • channel activity
  • ubiquitin protein ligase binding
  • identical protein binding
  • BH3 domain binding
  • digestive tract morphogenesis
  • regulation of mitochondrial membrane potential
  • focal adhesion assembly
  • negative regulation of reactive oxygen species metabolic process
  • positive regulation of cell growth
  • negative regulation of intrinsic apoptotic signaling pathway
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • cochlear nucleus development
  • reactive oxygen species metabolic process
  • B cell receptor signaling pathway
  • response to UV-B
  • regulation of gene expression
  • positive regulation of multicellular organism growth
  • glomerulus development
  • spleen development
  • negative regulation of cell migration
  • negative regulation of autophagy
  • negative regulation of cell growth
  • T cell homeostasis
  • CD8-positive, alpha-beta T cell lineage commitment
  • peptidyl-threonine phosphorylation
  • regulation of protein stability
  • cell aging
  • B cell proliferation
  • cellular response to organic substance
  • negative regulation of anoikis
  • melanin metabolic process
  • male gonad development
  • defense response to virus
  • negative regulation of osteoblast proliferation
  • response to glucocorticoid
  • behavioral fear response
  • regulation of cell-matrix adhesion
  • mesenchymal cell development
  • protein dephosphorylation
  • homeostasis of number of cells within a tissue
  • lymphoid progenitor cell differentiation
  • regulation of calcium ion transport
  • axon regeneration
  • protein polyubiquitination
  • intrinsic apoptotic signaling pathway in response to oxidative stress
  • negative regulation of cellular pH reduction
  • cellular response to DNA damage stimulus
  • response to cytokine
  • positive regulation of catalytic activity
  • melanocyte differentiation
  • response to toxic substance
  • ovarian follicle development
  • negative regulation of myeloid cell apoptotic process
  • negative regulation of mitochondrial depolarization
  • innate immune response
  • negative regulation of neuron apoptotic process
  • branching involved in ureteric bud morphogenesis
  • positive regulation of neuron maturation
  • negative regulation of ossification
  • organ growth
  • actin filament organization
  • negative regulation of retinal cell programmed cell death
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • ossification
  • oocyte development
  • response to drug
  • female pregnancy
  • axonogenesis
  • response to gamma radiation
  • metanephros development
  • pigment granule organization
  • transmembrane transport
  • intrinsic apoptotic signaling pathway
  • T cell differentiation in thymus
  • B cell lineage commitment
  • programmed cell death
  • response to ischemia
  • extrinsic apoptotic signaling pathway via death domain receptors
  • positive regulation of melanocyte differentiation
  • thymus development
  • regulation of mitochondrial membrane permeability
  • gland morphogenesis
  • positive regulation of intrinsic apoptotic signaling pathway
  • positive regulation of skeletal muscle fiber development
  • response to hydrogen peroxide
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
  • B cell homeostasis
  • regulation of transmembrane transporter activity
  • humoral immune response
  • neuron apoptotic process
  • hair follicle morphogenesis
  • ear development
  • post-embryonic development
  • peptidyl-serine phosphorylation
  • regulation of viral genome replication
  • cell growth
  • response to radiation
  • positive regulation of smooth muscle cell migration
  • negative regulation of apoptotic signaling pathway
  • endoplasmic reticulum calcium ion homeostasis
  • apoptotic process
  • response to nicotine
  • release of cytochrome c from mitochondria
  • negative regulation of G1/S transition of mitotic cell cycle
  • regulation of nitrogen utilization
  • cellular response to hypoxia
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
  • renal system process
  • negative regulation of apoptotic process
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • extrinsic apoptotic signaling pathway in absence of ligand
  • regulation of protein homodimerization activity
  • cellular response to glucose starvation
  • positive regulation of B cell proliferation
  • regulation of glycoprotein biosynthetic process
  • positive regulation of peptidyl-serine phosphorylation
  • response to iron ion
  • negative regulation of calcium ion transport into cytosol
  • regulation of protein heterodimerization activity
  • cytosol
  • cytoplasm
  • myelin sheath
  • mitochondrion
  • nuclear membrane
  • membrane
  • nucleus
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • pore complex
  • mitochondrial outer membrane
General FunctionUbiquitin protein ligase binding
Specific FunctionSuppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
Pfam Domain Function
Transmembrane Regions212-233
GenBank Protein ID179367
UniProtKB IDP10415
UniProtKB Entry NameBCL2_HUMAN
Cellular LocationMitochondrion outer membrane
Gene sequence
>lcl|BSEQ0021924|Apoptosis regulator Bcl-2 (BCL2)
GenBank Gene IDM13994
GeneCard IDNot Available
GenAtlas IDBCL2
Chromosome Location18
  1. Tsujimoto Y, Croce CM: Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5214-8. 3523487
  2. Eguchi Y, Ewert DL, Tsujimoto Y: Isolation and characterization of the chicken bcl-2 gene: expression in a variety of tissues including lymphoid and neuronal organs in adult and embryo. Nucleic Acids Res. 1992 Aug 25;20(16):4187-92. 1508712
  3. Cleary ML, Smith SD, Sklar J: Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19-28. 2875799
  4. Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P, Korsmeyer SJ: Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma. EMBO J. 1988 Jan;7(1):123-31. 2834197
  5. Hua C, Zorn S, Jensen JP, Coupland RW, Ko HS, Wright JJ, Bakhshi A: Consequences of the t(14;18) chromosomal translocation in follicular lymphoma: deregulated expression of a chimeric and mutated BCL-2 gene. Oncogene Res. 1988 Feb;2(3):263-75. 3285301
  6. Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. 16177791
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Tanaka S, Louie DC, Kant JA, Reed JC: Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas. Blood. 1992 Jan 1;79(1):229-37. 1339299
  9. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334-6. 2250705
  10. Yin XM, Oltvai ZN, Korsmeyer SJ: BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature. 1994 May 26;369(6478):321-3. 8183370
  11. Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimoto RI, Reed JC: BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 1997 Aug 15;16(16):4887-96. 9305631
  12. Cheng EH, Kirsch DG, Clem RJ, Ravi R, Kastan MB, Bedi A, Ueno K, Hardwick JM: Conversion of Bcl-2 to a Bax-like death effector by caspases. Science. 1997 Dec 12;278(5345):1966-8. 9395403
  13. Naumovski L, Cleary ML: The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M. Mol Cell Biol. 1996 Jul;16(7):3884-92. 8668206
  14. Ruvolo PP, Deng X, May WS: Phosphorylation of Bcl2 and regulation of apoptosis. Leukemia. 2001 Apr;15(4):515-22. 11368354
  15. Yamamoto K, Ichijo H, Korsmeyer SJ: BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol. 1999 Dec;19(12):8469-78. 10567572
  16. Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B: PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell. 2001 Mar;7(3):673-82. 11463391
  17. Qin W, Hu J, Guo M, Xu J, Li J, Yao G, Zhou X, Jiang H, Zhang P, Shen L, Wan D, Gu J: BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis. Biochem Biophys Res Commun. 2003 Aug 22;308(2):379-85. 12901880
  18. Kang CB, Tai J, Chia J, Yoon HS: The flexible loop of Bcl-2 is required for molecular interaction with immunosuppressant FK-506 binding protein 38 (FKBP38). FEBS Lett. 2005 Feb 28;579(6):1469-76. 15733859
  19. Jin S, Zhuo Y, Guo W, Field J: p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association. J Biol Chem. 2005 Jul 1;280(26):24698-705. Epub 2005 Apr 22. 15849194
  20. Chintharlapalli SR, Jasti M, Malladi S, Parsa KV, Ballestero RP, Gonzalez-Garcia M: BMRP is a Bcl-2 binding protein that induces apoptosis. J Cell Biochem. 2005 Feb 15;94(3):611-26. 15547950
  21. Portier BP, Taglialatela G: Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression. J Biol Chem. 2006 Dec 29;281(52):40493-502. Epub 2006 Nov 7. 17090549
  22. Bruey JM, Bruey-Sedano N, Luciano F, Zhai D, Balpai R, Xu C, Kress CL, Bailly-Maitre B, Li X, Osterman A, Matsuzawa S, Terskikh AV, Faustin B, Reed JC: Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell. 2007 Apr 6;129(1):45-56. 17418785
  23. Wei Y, Pattingre S, Sinha S, Bassik M, Levine B: JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008 Jun 20;30(6):678-88. doi: 10.1016/j.molcel.2008.06.001. 18570871
  24. Welch C, Santra MK, El-Assaad W, Zhu X, Huber WE, Keys RA, Teodoro JG, Green MR: Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer Res. 2009 Sep 1;69(17):6782-9. doi: 10.1158/0008-5472.CAN-09-0128. Epub 2009 Aug 25. 19706769
  25. Eliseev RA, Malecki J, Lester T, Zhang Y, Humphrey J, Gunter TE: Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect. J Biol Chem. 2009 Apr 10;284(15):9692-9. doi: 10.1074/jbc.M808750200. Epub 2009 Feb 19. 19228691
  26. Liu Y, Huo Z, Yan B, Lin X, Zhou ZN, Liang X, Zhu W, Liang D, Li L, Liu Y, Zhao H, Sun Y, Chen YH: Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):231-7. doi: 10.1016/j.bbrc.2010.09.037. Epub 2010 Sep 16. 20849813
  27. Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G: Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. J Biol Chem. 2010 Dec 3;285(49):38214-23. doi: 10.1074/jbc.M110.101469. Epub 2010 Oct 2. 20889974
  28. Zhang X, Weng C, Li Y, Wang X, Jiang C, Li X, Xu Y, Chen Q, Pan L, Tang H: Human Bop is a novel BH3-only member of the Bcl-2 protein family. Protein Cell. 2012 Oct;3(10):790-801. doi: 10.1007/s13238-012-2069-7. Epub 2012 Oct 11. 23055042
  29. Chiorazzi M, Rui L, Yang Y, Ceribelli M, Tishbi N, Maurer CW, Ranuncolo SM, Zhao H, Xu W, Chan WC, Jaffe ES, Gascoyne RD, Campo E, Rosenwald A, Ott G, Delabie J, Rimsza LM, Shaham S, Staudt LM: Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3943-8. doi: 10.1073/pnas.1217271110. Epub 2013 Feb 19. 23431138
  30. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  31. Petros AM, Medek A, Nettesheim DG, Kim DH, Yoon HS, Swift K, Matayoshi ED, Oltersdorf T, Fesik SW: Solution structure of the antiapoptotic protein bcl-2. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3012-7. Epub 2001 Feb 27. 11248023
  32. Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH: An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005 Jun 2;435(7042):677-81. Epub 2005 May 15. 15902208
  33. Bruncko M, Oost TK, Belli BA, Ding H, Joseph MK, Kunzer A, Martineau D, McClellan WJ, Mitten M, Ng SC, Nimmer PM, Oltersdorf T, Park CM, Petros AM, Shoemaker AR, Song X, Wang X, Wendt MD, Zhang H, Fesik SW, Rosenberg SH, Elmore SW: Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J Med Chem. 2007 Feb 22;50(4):641-62. Epub 2007 Jan 26. 17256834