Apoptosis regulator Bcl-2

NameApoptosis regulator Bcl-2
Synonyms
Gene NameBCL2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000491|Apoptosis regulator Bcl-2
MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPA
ASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLH
LTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY
LNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK
Number of residuesNone
Molecular Weight26265.66
Theoretical pI7.32
GO Classification
Functions
  • identical protein binding
  • sequence-specific DNA binding
  • protease binding
  • channel inhibitor activity
  • channel activity
  • protein homodimerization activity
  • ubiquitin protein ligase binding
  • BH3 domain binding
  • protein heterodimerization activity
Processes
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • focal adhesion assembly
  • ossification
  • negative regulation of reactive oxygen species metabolic process
  • negative regulation of retinal cell programmed cell death
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
  • B cell proliferation
  • B cell homeostasis
  • cell aging
  • regulation of protein homodimerization activity
  • regulation of nitrogen utilization
  • protein polyubiquitination
  • cellular response to hypoxia
  • intrinsic apoptotic signaling pathway in response to oxidative stress
  • transmembrane transport
  • B cell receptor signaling pathway
  • intrinsic apoptotic signaling pathway
  • response to UV-B
  • pigment granule organization
  • peptidyl-serine phosphorylation
  • response to glucocorticoid
  • regulation of viral genome replication
  • negative regulation of osteoblast proliferation
  • regulation of protein heterodimerization activity
  • ovarian follicle development
  • cellular response to glucose starvation
  • negative regulation of myeloid cell apoptotic process
  • negative regulation of autophagy
  • positive regulation of melanocyte differentiation
  • response to nicotine
  • regulation of calcium ion transport
  • release of cytochrome c from mitochondria
  • lymphoid progenitor cell differentiation
  • digestive tract morphogenesis
  • organ growth
  • regulation of mitochondrial membrane potential
  • actin filament organization
  • response to hydrogen peroxide
  • regulation of protein stability
  • positive regulation of skeletal muscle fiber development
  • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
  • response to toxic substance
  • extrinsic apoptotic signaling pathway in absence of ligand
  • melanocyte differentiation
  • metanephros development
  • cochlear nucleus development
  • reactive oxygen species metabolic process
  • response to gamma radiation
  • post-embryonic development
  • defense response to virus
  • response to iron ion
  • negative regulation of ossification
  • negative regulation of calcium ion transport into cytosol
  • positive regulation of neuron maturation
  • negative regulation of cell migration
  • extrinsic apoptotic signaling pathway via death domain receptors
  • response to ischemia
  • apoptotic process
  • homeostasis of number of cells within a tissue
  • response to drug
  • negative regulation of intrinsic apoptotic signaling pathway
  • female pregnancy
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • peptidyl-threonine phosphorylation
  • positive regulation of intrinsic apoptotic signaling pathway
  • CD8-positive, alpha-beta T cell lineage commitment
  • gland morphogenesis
  • negative regulation of apoptotic process
  • positive regulation of catalytic activity
  • programmed cell death
  • positive regulation of multicellular organism growth
  • axonogenesis
  • glomerulus development
  • B cell lineage commitment
  • male gonad development
  • ear development
  • melanin metabolic process
  • hair follicle morphogenesis
  • positive regulation of peptidyl-serine phosphorylation
  • branching involved in ureteric bud morphogenesis
  • negative regulation of cell growth
  • spleen development
  • regulation of mitochondrial membrane permeability
  • negative regulation of apoptotic signaling pathway
  • protein dephosphorylation
  • endoplasmic reticulum calcium ion homeostasis
  • mesenchymal cell development
  • positive regulation of cell growth
  • oocyte development
  • humoral immune response
  • cellular response to organic substance
  • T cell homeostasis
  • regulation of transmembrane transporter activity
  • cellular response to DNA damage stimulus
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
  • response to cytokine
  • renal system process
  • negative regulation of cellular pH reduction
  • regulation of gene expression
  • T cell differentiation in thymus
  • cell growth
  • behavioral fear response
  • neuron apoptotic process
  • negative regulation of anoikis
  • innate immune response
  • positive regulation of B cell proliferation
  • negative regulation of neuron apoptotic process
  • regulation of glycoprotein biosynthetic process
  • negative regulation of mitochondrial depolarization
  • thymus development
  • negative regulation of G1/S transition of mitotic cell cycle
  • response to radiation
  • axon regeneration
  • positive regulation of smooth muscle cell migration
  • regulation of cell-matrix adhesion
Components
  • cytoplasm
  • mitochondrion
  • mitochondrial outer membrane
  • membrane
  • nucleus
  • endoplasmic reticulum
  • cytosol
  • myelin sheath
  • endoplasmic reticulum membrane
  • nuclear membrane
  • pore complex
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).
Transmembrane Regions212-233
GenBank Protein ID
UniProtKB IDP10415
UniProtKB Entry Name
Cellular LocationMitochondrion outer membrane
Gene sequence
>lcl|BSEQ0021924|Apoptosis regulator Bcl-2 (BCL2)
ATGGCGCACGCTGGGAGAACAGGGTACGATAACCGGGAGATAGTGATGAAGTACATCCAT
TATAAGCTGTCGCAGAGGGGCTACGAGTGGGATGCGGGAGATGTGGGCGCCGCGCCCCCG
GGGGCCGCCCCCGCACCGGGCATCTTCTCCTCCCAGCCCGGGCACACGCCCCATCCAGCC
GCATCCCGGGACCCGGTCGCCAGGACCTCGCCGCTGCAGACCCCGGCTGCCCCCGGCGCC
GCCGCGGGGCCTGCGCTCAGCCCGGTGCCACCTGTGGTCCACCTGACCCTCCGCCAGGCC
GGCGACGACTTCTCCCGCCGCTACCGCCGCGACTTCGCCGAGATGTCCAGCCAGCTGCAC
CTGACGCCCTTCACCGCGCGGGGACGCTTTGCCACGGTGGTGGAGGAGCTCTTCAGGGAC
GGGGTGAACTGGGGGAGGATTGTGGCCTTCTTTGAGTTCGGTGGGGTCATGTGTGTGGAG
AGCGTCAACCGGGAGATGTCGCCCCTGGTGGACAACATCGCCCTGTGGATGACTGAGTAC
CTGAACCGGCACCTGCACACCTGGATCCAGGATAACGGAGGCTGGGATGCCTTTGTGGAA
CTGTACGGCCCCAGCATGCGGCCTCTGTTTGATTTCTCCTGGCTGTCTCTGAAGACTCTG
CTCAGTTTGGCCCTGGTGGGAGCTTGCATCACCCTGGGTGCCTATCTGGGCCACAAGTGA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC ID
Chromosome Location18
Locus18q21.33|18q21.3
References
  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 ]

From www.t3db.ca