Apoptosis regulator Bcl-2

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• BH3 domain binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• channel activity Source: BHF-UCL <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Inhibition of Bax channel-forming activity by Bcl-2."
    Antonsson B., Conti F., Ciavatta A., Montessuit S., Lewis S., Martinou I., Bernasconi L., Bernard A., Mermod J.J., Mazzei G., Maundrell K., Gambale F., Sadoul R., Martinou J.C.
    Science 277:370-372(1997) [PubMed] [Europe PMC] [Abstract]
• channel inhibitor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Inhibition of Bax channel-forming activity by Bcl-2."
    Antonsson B., Conti F., Ciavatta A., Montessuit S., Lewis S., Martinou I., Bernasconi L., Bernard A., Mermod J.J., Mazzei G., Maundrell K., Gambale F., Sadoul R., Martinou J.C.
    Science 277:370-372(1997) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • "A short Nur77-derived peptide converts Bcl-2 from a protector to a killer."
    Kolluri S.K., Zhu X., Zhou X., Lin B., Chen Y., Sun K., Tian X., Town J., Cao X., Lin F., Zhai D., Kitada S., Luciano F., O'Donnell E., Cao Y., He F., Lin J., Reed J.C., Satterthwait A.C., Zhang X.K.
    Cancer Cell 14:285-298(2008) [PubMed] [Europe PMC] [Abstract]
  • "The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4."
    Huang D.C., Adams J.M., Cory S.
    EMBO J. 17:1029-1039(1998) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: UniProtKBInferred from direct assayⁱ
  • "The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore."
    Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L.A., Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.-P., Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C., Roques B.P., Kroemer G.
    J. Exp. Med. 191:33-46(2000) [PubMed] [Europe PMC] [Abstract]
• protein heterodimerization activity Source: UniProtKBInferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: UniProtKBInferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• protein phosphatase 2A binding Source: Ensembl
• repressing transcription factor binding Source: ARUK-UCLInferred from physical interactionⁱ
  • "WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization."
    Tomita Y., Marchenko N., Erster S., Nemajerova A., Dehner A., Klein C., Pan H., Kessler H., Pancoska P., Moll U.M.
    J. Biol. Chem. 281:8600-8606(2006) [PubMed] [Europe PMC] [Abstract]
• sequence-specific DNA binding Source: MGIInferred from direct assayⁱ
  • "Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability."
    McGill G.G., Horstmann M., Widlund H.R., Du J., Motyckova G., Nishimura E.K., Lin Y.L., Ramaswamy S., Avery W., Ding H.F., Jordan S.A., Jackson I.J., Korsmeyer S.J., Golub T.R., Fisher D.E.
    Cell 109:707-718(2002) [PubMed] [Europe PMC] [Abstract]
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.29

    "Parkin mono-ubiquitinates Bcl-2 and regulates autophagy."
    Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G.
    J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: UBIQUITINATION BY PRKN.

GO - Biological processⁱ

• actin filament organization Source: Ensembl
• apoptotic process Source: MGIInferred from direct assayⁱ
  • "Isolation of a strain of Streptococcus pneumoniae multiresistant to antibiotics."
    Dublanchet A., Durieux R.
    Nouv Presse Med 8:872-872(1979) [PubMed] [Europe PMC] [Abstract]
  • "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes."
    Lam M., Dubyak G., Chen L., Nunez G., Miesfeld R.L., Distelhorst C.W.
    Proc. Natl. Acad. Sci. U.S.A. 91:6569-6573(1994) [PubMed] [Europe PMC] [Abstract]
• axonogenesis Source: Ensembl
• axon regeneration Source: Ensembl
• B cell homeostasis Source: Ensembl
• B cell lineage commitment Source: Ensembl
• B cell proliferation Source: MGIInferred from direct assayⁱ
  • "Bcl-2 confers growth and survival advantage to interleukin 7-dependent early pre-B cells which become factor independent by a multistep process in culture."
    Borzillo G.V., Endo K., Tsujimoto Y.
    Oncogene 7:869-876(1992) [PubMed] [Europe PMC] [Abstract]
• B cell receptor signaling pathway Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
    Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
    Clin. Cancer Res. 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
• behavioral fear response Source: Ensembl
• branching involved in ureteric bud morphogenesis Source: Ensembl
• CD8-positive, alpha-beta T cell lineage commitment Source: Ensembl
• cell aging Source: Ensembl
• cell-cell adhesion Source: Ensembl
• cellular response to DNA damage stimulus Source: UniProtKBInferred from mutant phenotypeⁱ
  • "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
    Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
    Clin. Cancer Res. 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
• cellular response to glucose starvation Source: Ensembl
• cellular response to hypoxia Source: Ensembl
• cochlear nucleus development Source: Ensembl
• cytokine-mediated signaling pathway Source: Reactome
• defense response to virus Source: UniProtKBInferred from direct assayⁱ
  • "The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore."
    Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L.A., Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.-P., Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C., Roques B.P., Kroemer G.
    J. Exp. Med. 191:33-46(2000) [PubMed] [Europe PMC] [Abstract]
• digestive tract morphogenesis Source: Ensembl
• ear development Source: Ensembl
• endoplasmic reticulum calcium ion homeostasis Source: UniProtKB <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "No death without life: vital functions of apoptotic effectors."
    Galluzzi L., Joza N., Tasdemir E., Maiuri M.C., Hengartner M., Abrams J.M., Tavernarakis N., Penninger J., Madeo F., Kroemer G.
    Cell Death Differ. 15:1113-1123(2008) [PubMed] [Europe PMC] [Abstract]
• extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• extrinsic apoptotic signaling pathway via death domain receptors Source: MGIInferred from direct assayⁱ
  • "Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death."
    Lee J.H., Takahashi T., Yasuhara N., Inazawa J., Kamada S., Tsujimoto Y.
    Oncogene 18:6183-6190(1999) [PubMed] [Europe PMC] [Abstract]
• female pregnancy Source: UniProtKB <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "The immunolocalization of Bcl-2 in human term placenta."
    Axt-Fliedner R., Friedrich M., Kordina A., Wasemann C., Mink D., Reitnauer K., Schmidt W.
    Clin Exp Obstet Gynecol 28:144-147(2001) [PubMed] [Europe PMC] [Abstract]
• focal adhesion assembly Source: Ensembl
• gland morphogenesis Source: Ensembl
• glomerulus development Source: Ensembl
• hair follicle morphogenesis Source: Ensembl
• homeostasis of number of cells within a tissue Source: Ensembl
• humoral immune response Source: UniProtKBTraceable author statementⁱ
  • "Bcl-2 maintains B cell memory."
    Nunez G., Hockenbery D., McDonnell T.J., Sorensen C.M., Korsmeyer S.J.
    Nature 353:71-73(1991) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: MGIInferred from direct assayⁱ
  • "Proapoptotic BAX and BAK control multiple initiator caspases."
    Ruiz-Vela A., Opferman J.T., Cheng E.H., Korsmeyer S.J.
    EMBO Rep. 6:379-385(2005) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway in response to oxidative stress Source: Ensembl
• lymphoid progenitor cell differentiation Source: Ensembl
• male gonad development Source: Ensembl
• melanin metabolic process Source: Ensembl
• melanocyte differentiation Source: Ensembl
• mesenchymal cell development Source: Ensembl
• metanephros development Source: Ensembl
• negative regulation of anoikis Source: UniProtKBInferred from mutant phenotypeⁱ
  • "A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors."
    Jan Y., Matter M., Pai J.-T., Chen Y.-L., Pilch J., Komatsu M., Ong E., Fukuda M., Ruoslahti E.
    Cell 116:751-762(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Regulation of acidification and apoptosis by SHP-1 and Bcl-2."
    Thangaraju M., Sharma K., Leber B., Andrews D.W., Shen S.H., Srikant C.B.
    J. Biol. Chem. 274:29549-29557(1999) [PubMed] [Europe PMC] [Abstract]
  • "The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore."
    Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L.A., Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.-P., Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C., Roques B.P., Kroemer G.
    J. Exp. Med. 191:33-46(2000) [PubMed] [Europe PMC] [Abstract]
  • "Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked."
    Yang J., Liu X., Bhalla K., Kim C.N., Ibrado A.M., Cai J., Peng T.I., Jones D.P., Wang X.
    Science 275:1129-1132(1997) [PubMed] [Europe PMC] [Abstract]
• negative regulation of apoptotic signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Identification of a novel proapoptotic function of resveratrol in fat cells: SIRT1-independent sensitization to TRAIL-induced apoptosis."
    Mader I., Wabitsch M., Debatin K.M., Fischer-Posovszky P., Fulda S.
    FASEB J. 24:1997-2009(2010) [PubMed] [Europe PMC] [Abstract]
• negative regulation of autophagy Source: UniProtKBTraceable author statementⁱ
  • "No death without life: vital functions of apoptotic effectors."
    Galluzzi L., Joza N., Tasdemir E., Maiuri M.C., Hengartner M., Abrams J.M., Tavernarakis N., Penninger J., Madeo F., Kroemer G.
    Cell Death Differ. 15:1113-1123(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of calcium ion transport into cytosol Source: Ensembl
• negative regulation of cell growth Source: Ensembl
• negative regulation of cell migration Source: Ensembl
• negative regulation of cellular pH reduction Source: UniProtKBInferred from direct assayⁱ
  • "Regulation of acidification and apoptosis by SHP-1 and Bcl-2."
    Thangaraju M., Sharma K., Leber B., Andrews D.W., Shen S.H., Srikant C.B.
    J. Biol. Chem. 274:29549-29557(1999) [PubMed] [Europe PMC] [Abstract]
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe “traditional” genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death."
    Oltvai Z.N., Milliman C.L., Korsmeyer S.J.
    Cell 74:609-619(1993) [PubMed] [Europe PMC] [Abstract]
• negative regulation of G1/S transition of mitotic cell cycle Source: Ensembl
• negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • "ASPP proteins specifically stimulate the apoptotic function of p53."
    Samuels-Lev Y., O'Connor D.J., Bergamaschi D., Trigiante G., Hsieh J.-K., Zhong S., Campargue I., Naumovski L., Crook T., Lu X.
    Mol. Cell 8:781-794(2001) [PubMed] [Europe PMC] [Abstract]
• negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: BHF-UCLTraceable author statementⁱ
  • "The bcl-2 oncogene and apoptosis."
    Hockenbery D.M.
    Semin. Immunol. 4:413-420(1992) [PubMed] [Europe PMC] [Abstract]
• negative regulation of mitochondrial depolarization Source: UniProtKBTraceable author statementⁱ
  • "Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked."
    Yang J., Liu X., Bhalla K., Kim C.N., Ibrado A.M., Cai J., Peng T.I., Jones D.P., Wang X.
    Science 275:1129-1132(1997) [PubMed] [Europe PMC] [Abstract]
• negative regulation of myeloid cell apoptotic process Source: Ensembl
• negative regulation of neuron apoptotic process Source: MGIInferred from direct assayⁱ
  • "Role of BCL-2 in the survival and function of developing and mature sympathetic neurons."
    Greenlund L.J., Korsmeyer S.J., Johnson E.M. Jr.
    Neuron 15:649-661(1995) [PubMed] [Europe PMC] [Abstract]
• negative regulation of ossification Source: Ensembl
• negative regulation of osteoblast proliferation Source: Ensembl
• negative regulation of reactive oxygen species metabolic process Source: Ensembl
• negative regulation of retinal cell programmed cell death Source: Ensembl
• neuron apoptotic process Source: HGNC-UCLTraceable author statementⁱ
  • "Inhibition of mitochondrial neural cell death pathways by protein transduction of Bcl-2 family proteins."
    Soane L., Fiskum G.
    J. Bioenerg. Biomembr. 37:179-190(2005) [PubMed] [Europe PMC] [Abstract]
• oocyte development Source: Ensembl
• organ growth Source: Ensembl
• ossification Source: Ensembl
• ovarian follicle development Source: Ensembl
• peptidyl-serine phosphorylation Source: Ensembl
• peptidyl-threonine phosphorylation Source: Ensembl
• pigment granule organization Source: Ensembl
• positive regulation of B cell proliferation Source: UniProtKBInferred from mutant phenotypeⁱ
  • "ATM, CTLA4, MNDA, and HEM1 in high versus low CD38 expressing B-cell chronic lymphocytic leukemia."
    Joshi A.D., Hegde G.V., Dickinson J.D., Mittal A.K., Lynch J.C., Eudy J.D., Armitage J.O., Bierman P.J., Bociek R.G., Devetten M.P., Vose J.M., Joshi S.S.
    Clin. Cancer Res. 13:5295-5304(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of catalytic activity Source: Ensembl
• positive regulation of cell growth Source: MGIInferred from direct assayⁱ
  • "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes."
    Lam M., Dubyak G., Chen L., Nunez G., Miesfeld R.L., Distelhorst C.W.
    Proc. Natl. Acad. Sci. U.S.A. 91:6569-6573(1994) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell population proliferation Source: ARUK-UCLInferred from genetic interactionⁱ
  • "miR-204-5p acts as a tumor suppressor by targeting matrix metalloproteinases-9 and B-cell lymphoma-2 in malignant melanoma."
    Luan W., Qian Y., Ni X., Bu X., Xia Y., Wang J., Ruan H., Ma S., Xu B.
    Onco Targets Ther 10:1237-1246(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of intrinsic apoptotic signaling pathway Source: Reactome
• positive regulation of melanocyte differentiation Source: Ensembl
• positive regulation of multicellular organism growth Source: Ensembl
• positive regulation of neuron maturation Source: Ensembl
• positive regulation of peptidyl-serine phosphorylation Source: Ensembl
• positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
• positive regulation of skeletal muscle fiber development Source: Ensembl
• positive regulation of smooth muscle cell migration Source: Ensembl
• post-embryonic development Source: Ensembl
• protein dephosphorylation Source: Ensembl
• protein polyubiquitination Source: MGIInferred from direct assayⁱ
  • "PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum."
    Lin S.S., Bassik M.C., Suh H., Nishino M., Arroyo J.D., Hahn W.C., Korsmeyer S.J., Roberts T.M.
    J. Biol. Chem. 281:23003-23012(2006) [PubMed] [Europe PMC] [Abstract]
• reactive oxygen species metabolic process Source: Ensembl
• regulation of calcium ion transport Source: MGIInferred from direct assayⁱ
  • "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes."
    Lam M., Dubyak G., Chen L., Nunez G., Miesfeld R.L., Distelhorst C.W.
    Proc. Natl. Acad. Sci. U.S.A. 91:6569-6573(1994) [PubMed] [Europe PMC] [Abstract]
• regulation of cell-matrix adhesion Source: Ensembl
• regulation of gene expression Source: Ensembl
• regulation of glycoprotein biosynthetic process Source: Ensembl
• regulation of mitochondrial membrane permeability Source: HGNC-UCL <p>Inferred from Sequence or Structural Similarity <br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide-go-evidence-codes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria."
    Narita M., Shimizu S., Ito T., Chittenden T., Lutz R.J., Matsuda H., Tsujimoto Y.
    Proc. Natl. Acad. Sci. U.S.A. 95:14681-14686(1998) [PubMed] [Europe PMC] [Abstract]
• regulation of mitochondrial membrane potential Source: HGNC-UCLInferred from sequence or structural similarityⁱ
  • "Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria."
    Narita M., Shimizu S., Ito T., Chittenden T., Lutz R.J., Matsuda H., Tsujimoto Y.
    Proc. Natl. Acad. Sci. U.S.A. 95:14681-14686(1998) [PubMed] [Europe PMC] [Abstract]
• regulation of nitrogen utilization Source: Ensembl
• regulation of protein heterodimerization activity Source: UniProtKBInferred from direct assayⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• regulation of protein homodimerization activity Source: UniProtKBInferred from direct assayⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• regulation of protein stability Source: Ensembl
• regulation of transmembrane transporter activity Source: BHF-UCLInferred from direct assayⁱ
  • "Inhibition of Bax channel-forming activity by Bcl-2."
    Antonsson B., Conti F., Ciavatta A., Montessuit S., Lewis S., Martinou I., Bernasconi L., Bernard A., Mermod J.J., Mazzei G., Maundrell K., Gambale F., Sadoul R., Martinou J.C.
    Science 277:370-372(1997) [PubMed] [Europe PMC] [Abstract]
• regulation of viral genome replication Source: Ensembl
• release of cytochrome c from mitochondria Source: HGNC-UCLInferred from sequence or structural similarityⁱ
  • "Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria."
    Narita M., Shimizu S., Ito T., Chittenden T., Lutz R.J., Matsuda H., Tsujimoto Y.
    Proc. Natl. Acad. Sci. U.S.A. 95:14681-14686(1998) [PubMed] [Europe PMC] [Abstract]
• renal system process Source: Ensembl
• response to cytokine Source: MGIInferred from direct assayⁱ
  • "The apoptosis and proliferation of SAC-activated B cells by IL-10 are associated with changes in Bcl-2, Bcl-xL, and Mcl-1 expression."
    Li L., Krajewski S., Reed J.C., Choi Y.S.
    Cell. Immunol. 178:33-41(1997) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: MGIInferred from direct assayⁱ
  • "Isolation of a strain of Streptococcus pneumoniae multiresistant to antibiotics."
    Dublanchet A., Durieux R.
    Nouv Presse Med 8:872-872(1979) [PubMed] [Europe PMC] [Abstract]
• response to gamma radiation Source: Ensembl
• response to glucocorticoid Source: Ensembl
• response to hydrogen peroxide Source: Ensembl
• response to iron ion Source: UniProtKBInferred from direct assayⁱ
  • "Iron induces Bcl-2 expression in human dermal microvascular endothelial cells."
    Simonart T., Degraef C., Stordeur P., Noel J.C., Mosselmans R., Van Vooren J.P., Parent D., Boelaert J.R., Heenen M., Galand P.
    Free Radic. Res. 34:221-235(2001) [PubMed] [Europe PMC] [Abstract]
• response to ischemia Source: Ensembl
• response to nicotine Source: UniProtKBInferred from direct assayⁱ
  • "A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis."
    Mai H., May W.S., Gao F., Jin Z., Deng X.
    J. Biol. Chem. 278:1886-1891(2003) [PubMed] [Europe PMC] [Abstract]
• response to radiation Source: UniProtKBNon-traceable author statementⁱ
  • "Medium from irradiated cells induces dose-dependent mitochondrial changes and BCL2 responses in unirradiated human keratinocytes."
    Maguire P., Mothersill C., Seymour C., Lyng F.M.
    Radiat. Res. 163:384-390(2005) [PubMed] [Europe PMC] [Abstract]
• response to toxic substance Source: HGNC-UCLInferred from direct assayⁱ
  • "T-2 toxin induces apoptosis, and selenium partly blocks, T-2 toxin induced apoptosis in chondrocytes through modulation of the Bax/Bcl-2 ratio."
    Chen J., Chu Y., Cao J., Yang Z., Guo X., Wang Z.
    Food Chem. Toxicol. 44:567-573(2006) [PubMed] [Europe PMC] [Abstract]
• response to UV-B Source: Ensembl
• spleen development Source: Ensembl
• T cell differentiation in thymus Source: Ensembl
• T cell homeostasis Source: Ensembl
• thymus development Source: Ensembl

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Mutagenesis

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Sites

Keywords - PTMⁱ

Proteomic databases

PTM databases

Miscellaneous databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• BH3 domain binding Source: UniProtKBInferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • "A short Nur77-derived peptide converts Bcl-2 from a protector to a killer."
    Kolluri S.K., Zhu X., Zhou X., Lin B., Chen Y., Sun K., Tian X., Town J., Cao X., Lin F., Zhai D., Kitada S., Luciano F., O'Donnell E., Cao Y., He F., Lin J., Reed J.C., Satterthwait A.C., Zhang X.K.
    Cancer Cell 14:285-298(2008) [PubMed] [Europe PMC] [Abstract]
  • "The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4."
    Huang D.C., Adams J.M., Cory S.
    EMBO J. 17:1029-1039(1998) [PubMed] [Europe PMC] [Abstract]
• protease binding Source: UniProtKBInferred from direct assayⁱ
  • "The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore."
    Jacotot E., Ravagnan L., Loeffler M., Ferri K.F., Vieira H.L.A., Zamzami N., Costantini P., Druillennec S., Hoebeke J., Briand J.-P., Irinopoulou T., Daugas E., Susin S.A., Cointe D., Xie Z.H., Reed J.C., Roques B.P., Kroemer G.
    J. Exp. Med. 191:33-46(2000) [PubMed] [Europe PMC] [Abstract]
• protein heterodimerization activity Source: UniProtKBInferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: UniProtKBInferred from physical interactionⁱ
  • "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members."
    Diaz J.L., Oltersdorf T., Horne W., McConnell M., Wilson G., Weeks S., Garcia T., Fritz L.C.
    J. Biol. Chem. 272:11350-11355(1997) [PubMed] [Europe PMC] [Abstract]
• protein phosphatase 2A binding Source: Ensembl
• repressing transcription factor binding Source: ARUK-UCLInferred from physical interactionⁱ
  • "WT p53, but not tumor-derived mutants, bind to Bcl2 via the DNA binding domain and induce mitochondrial permeabilization."
    Tomita Y., Marchenko N., Erster S., Nemajerova A., Dehner A., Klein C., Pan H., Kessler H., Pancoska P., Moll U.M.
    J. Biol. Chem. 281:8600-8606(2006) [PubMed] [Europe PMC] [Abstract]
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.29

    "Parkin mono-ubiquitinates Bcl-2 and regulates autophagy."
    Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G.
    J. Biol. Chem. 285:38214-38223(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: UBIQUITINATION BY PRKN.

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Motif

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS 
        60         70         80         90        100
SQPGHTPHPA ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA 
       110        120        130        140        150
GDDFSRRYRR DFAEMSSQLH LTPFTARGRF ATVVEELFRD GVNWGRIVAF 
       160        170        180        190        200
FEFGGVMCVE SVNREMSPLV DNIALWMTEY LNRHLHTWIQ DNGGWDAFVE 
       210        220        230 
LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK             

        10         20         30         40         50
MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS 
        60         70         80         90        100
SQPGHTPHPA ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA 
       110        120        130        140        150
GDDFSRRYRR DFAEMSSQLH LTPFTARGRF ATVVEELFRD GVNWGRIVAF 
       160        170        180        190        200
FEFGGVMCVE SVNREMSPLV DNIALWMTEY LNRHLHTWIQ DNGGWVGALG 

DVSLG                                                  

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases