BCL2_HUMAN
ID BCL2_HUMAN Reviewed; 239 AA.
AC P10415; C9JHD5; P10416; Q13842; Q16197;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 03-AUG-2022, entry version 260.
DE RecName: Full=Apoptosis regulator Bcl-2;
GN Name=BCL2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RX PubMed=3523487; DOI=10.1073/pnas.83.14.5214;
RA Tsujimoto Y., Croce C.M.;
RT "Analysis of the structure, transcripts, and protein products of bcl-2, the
RT gene involved in human follicular lymphoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5214-5218(1986).
RN [2]
RP SEQUENCE REVISION TO 96; 110 AND 237, AND FUNCTION.
RX PubMed=1508712; DOI=10.1093/nar/20.16.4187;
RA Eguchi Y., Ewert D.L., Tsujimoto Y.;
RT "Isolation and characterization of the chicken bcl-2 gene: expression in a
RT variety of tissues including lymphoid and neuronal organs in adult and
RT embryo.";
RL Nucleic Acids Res. 20:4187-4192(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND CHROMOSOMAL TRANSLOCATION.
RX PubMed=2875799; DOI=10.1016/0092-8674(86)90362-4;
RA Cleary M.L., Smith S.D., Sklar J.;
RT "Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-
RT 2/immunoglobulin transcript resulting from the t(14;18) translocation.";
RL Cell 47:19-28(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND VARIANT SER-7.
RX PubMed=2834197; DOI=10.1002/j.1460-2075.1988.tb02791.x;
RA Seto M., Jaeger U., Hockett R.D., Graninger W., Bennett S., Goldman P.,
RA Korsmeyer S.J.;
RT "Alternative promoters and exons, somatic mutation and deregulation of the
RT Bcl-2-Ig fusion gene in lymphoma.";
RL EMBO J. 7:123-131(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT SER-7, AND CHROMOSOMAL
RP TRANSLOCATION.
RX PubMed=3285301;
RA Hua C., Zorn S., Jensen J.P., Coupland R.W., Ko H.S., Wright J.J.,
RA Bakhshi A.;
RT "Consequences of the t(14;18) chromosomal translocation in follicular
RT lymphoma: deregulated expression of a chimeric and mutated BCL-2 gene.";
RL Oncogene Res. 2:263-275(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-43.
RG NIEHS SNPs program;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-131 (ISOFORM ALPHA), AND VARIANTS
RP NON-HODGKIN LYMPHOMA SER-59 AND ILE-93.
RX PubMed=1339299;
RA Tanaka S., Louie D.C., Kant J.A., Reed J.C.;
RT "Frequent incidence of somatic mutations in translocated BCL2 oncogenes of
RT non-Hodgkin's lymphomas.";
RL Blood 79:229-237(1992).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=2250705; DOI=10.1038/348334a0;
RA Hockenbery D., Nunez G., Milliman C., Schreiber R.D., Korsmeyer S.J.;
RT "Bcl-2 is an inner mitochondrial membrane protein that blocks programmed
RT cell death.";
RL Nature 348:334-336(1990).
RN [12]
RP FUNCTION, INTERACTION WITH BAX, HOMODIMERIZATION, SUBUNIT, AND MUTAGENESIS
RP OF 138-PHE--GLY-141; TRP-144; GLY-145; ARG-146; TRP-188; GLN-190; ASP-191;
RP ASN-192; 194-GLY--ALA-197 AND GLU-200.
RX PubMed=8183370; DOI=10.1038/369321a0;
RA Yin X.-M., Oltvai Z.N., Korsmeyer S.J.;
RT "BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and
RT heterodimerization with Bax.";
RL Nature 369:321-323(1994).
RN [13]
RP INTERACTION WITH BAG1.
RX PubMed=9305631; DOI=10.1093/emboj/16.16.4887;
RA Takayama S., Bimston D.N., Matsuzawa S.-I., Freeman B.C., Aime-Sempe C.,
RA Xie Z., Morimoto R.I., Reed J.C.;
RT "BAG-1 modulates the chaperone activity of Hsp70/Hsc70.";
RL EMBO J. 16:4887-4896(1997).
RN [14]
RP CLEAVAGE BY CASPASES, AND MUTAGENESIS OF ASP-34 AND ASP-64.
RX PubMed=9395403; DOI=10.1126/science.278.5345.1966;
RA Cheng E.H.-Y., Kirsch D.G., Clem R.J., Ravi R., Kastan M.B., Bedi A.,
RA Ueno K., Hardwick J.M.;
RT "Conversion of Bcl-2 to a Bax-like death effector by caspases.";
RL Science 278:1966-1968(1997).
RN [15]
RP INTERACTION WITH TP53BP2.
RX PubMed=8668206; DOI=10.1128/mcb.16.7.3884;
RA Naumovski L., Cleary M.L.;
RT "The p53-binding protein 53BP2 also interacts with Bcl2 and impedes cell
RT cycle progression at G2/M.";
RL Mol. Cell. Biol. 16:3884-3892(1996).
RN [16]
RP REVIEW ON PHOSPHORYLATION.
RX PubMed=11368354; DOI=10.1038/sj.leu.2402090;
RA Ruvolo P.P., Deng X., May W.S.;
RT "Phosphorylation of Bcl2 and regulation of apoptosis.";
RL Leukemia 15:515-522(2001).
RN [17]
RP PHOSPHORYLATION BY ASK1/JNK1.
RX PubMed=10567572; DOI=10.1128/mcb.19.12.8469;
RA Yamamoto K., Ichijo H., Korsmeyer S.J.;
RT "BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein
RT kinase pathway normally activated at G(2)/M.";
RL Mol. Cell. Biol. 19:8469-8478(1999).
RN [18]
RP INTERACTION WITH BBC3 AND BCL2L1.
RX PubMed=11463391; DOI=10.1016/s1097-2765(01)00213-1;
RA Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B.;
RT "PUMA induces the rapid apoptosis of colorectal cancer cells.";
RL Mol. Cell 7:673-682(2001).
RN [19]
RP INTERACTION WITH BNIPL.
RX PubMed=12901880; DOI=10.1016/s0006-291x(03)01387-1;
RA Qin W., Hu J., Guo M., Xu J., Li J., Yao G., Zhou X., Jiang H., Zhang P.,
RA Shen L., Wan D., Gu J.;
RT "BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in
RT apoptosis.";
RL Biochem. Biophys. Res. Commun. 308:379-385(2003).
RN [20]
RP INTERACTION WITH FKBP8.
RX PubMed=15733859; DOI=10.1016/j.febslet.2005.01.053;
RA Kang C.B., Tai J., Chia J., Yoon H.S.;
RT "The flexible loop of Bcl-2 is required for molecular interaction with
RT immunosuppressant FK-506 binding protein 38 (FKBP38).";
RL FEBS Lett. 579:1469-1476(2005).
RN [21]
RP INTERACTION WITH RAF1.
RX PubMed=15849194; DOI=10.1074/jbc.m413374200;
RA Jin S., Zhuo Y., Guo W., Field J.;
RT "p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates
RT its mitochondrial localization, phosphorylation of BAD, and Bcl-2
RT association.";
RL J. Biol. Chem. 280:24698-24705(2005).
RN [22]
RP INTERACTION WITH MRPL41.
RX PubMed=15547950; DOI=10.1002/jcb.20292;
RA Chintharlapalli S.R., Jasti M., Malladi S., Parsa K.V.L., Ballestero R.P.,
RA Gonzalez-Garcia M.;
RT "BMRP is a Bcl-2 binding protein that induces apoptosis.";
RL J. Cell. Biochem. 94:611-626(2005).
RN [23]
RP INTERACTION WITH FKBP8.
RX PubMed=17090549; DOI=10.1074/jbc.m606181200;
RA Portier B.P., Taglialatela G.;
RT "Bcl-2 localized at the nuclear compartment induces apoptosis after
RT transient overexpression.";
RL J. Biol. Chem. 281:40493-40502(2006).
RN [24]
RP FUNCTION, INTERACTION WITH NLRP1, DOMAIN, AND MUTAGENESIS OF GLY-145.
RX PubMed=17418785; DOI=10.1016/j.cell.2007.01.045;
RA Bruey J.M., Bruey-Sedano N., Luciano F., Zhai D., Balpai R., Xu C.,
RA Kress C.L., Bailly-Maitre B., Li X., Osterman A., Matsuzawa S.,
RA Terskikh A.V., Faustin B., Reed J.C.;
RT "Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by
RT interaction with NALP1.";
RL Cell 129:45-56(2007).
RN [25]
RP PHOSPHORYLATION AT THR-69; SER-70 AND SER-87 BY MAPK8/JNK1, INTERACTION
RP WITH BECN1, AND FUNCTION.
RX PubMed=18570871; DOI=10.1016/j.molcel.2008.06.001;
RA Wei Y., Pattingre S., Sinha S., Bassik M., Levine B.;
RT "JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced
RT autophagy.";
RL Mol. Cell 30:678-688(2008).
RN [26]
RP INTERACTION WITH G0S2.
RX PubMed=19706769; DOI=10.1158/0008-5472.can-09-0128;
RA Welch C., Santra M.K., El-Assaad W., Zhu X., Huber W.E., Keys R.A.,
RA Teodoro J.G., Green M.R.;
RT "Identification of a protein, G0S2, that lacks Bcl-2 homology domains and
RT interacts with and antagonizes Bcl-2.";
RL Cancer Res. 69:6782-6789(2009).
RN [27]
RP INTERACTION WITH PPIF.
RX PubMed=19228691; DOI=10.1074/jbc.m808750200;
RA Eliseev R.A., Malecki J., Lester T., Zhang Y., Humphrey J., Gunter T.E.;
RT "Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect.";
RL J. Biol. Chem. 284:9692-9699(2009).
RN [28]
RP INTERACTION WITH EGLN3.
RX PubMed=20849813; DOI=10.1016/j.bbrc.2010.09.037;
RA Liu Y., Huo Z., Yan B., Lin X., Zhou Z.N., Liang X., Zhu W., Liang D.,
RA Li L., Liu Y., Zhao H., Sun Y., Chen Y.H.;
RT "Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced
RT apoptosis in H9c2 cells.";
RL Biochem. Biophys. Res. Commun. 401:231-237(2010).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BECN1 AND AMBRA1.
RX PubMed=21358617; DOI=10.1038/emboj.2011.49;
RA Strappazzon F., Vietri-Rudan M., Campello S., Nazio F., Florenzano F.,
RA Fimia G.M., Piacentini M., Levine B., Cecconi F.;
RT "Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.";
RL EMBO J. 30:1195-1208(2011).
RN [30]
RP FUNCTION, AND UBIQUITINATION BY PRKN.
RX PubMed=20889974; DOI=10.1074/jbc.m110.101469;
RA Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G.;
RT "Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.";
RL J. Biol. Chem. 285:38214-38223(2010).
RN [31]
RP INTERACTION WITH RTL10/BOP.
RX PubMed=23055042; DOI=10.1007/s13238-012-2069-7;
RA Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L.,
RA Tang H.;
RT "Human Bop is a novel BH3-only member of the Bcl-2 protein family.";
RL Protein Cell 3:790-801(2012).
RN [32]
RP INTERACTION WITH FBXO10, UBIQUITINATION, AND IDENTIFICATION IN THE
RP SCF(FBXO10) COMPLEX.
RX PubMed=23431138; DOI=10.1073/pnas.1217271110;
RA Chiorazzi M., Rui L., Yang Y., Ceribelli M., Tishbi N., Maurer C.W.,
RA Ranuncolo S.M., Zhao H., Xu W., Chan W.C., Jaffe E.S., Gascoyne R.D.,
RA Campo E., Rosenwald A., Ott G., Delabie J., Rimsza L.M., Shaham S.,
RA Staudt L.M.;
RT "Related F-box proteins control cell death in Caenorhabditis elegans and
RT human lymphoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:3943-3948(2013).
RN [33]
RP INTERACTION WITH BAX AND IRF3.
RX PubMed=25609812; DOI=10.1128/jvi.02959-14;
RA Wei B., Cui Y., Huang Y., Liu H., Li L., Li M., Ruan K.C., Zhou Q.,
RA Wang C.;
RT "Tom70 mediates Sendai virus-induced apoptosis on mitochondria.";
RL J. Virol. 89:3804-3818(2015).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [35]
RP IDENTIFICATION IN A COMPLEX WITH SEPTIN4 AND XIAP, INTERACTION WITH SEPTIN4
RP ISOFORM ARTS AND XIAP, AND UBIQUITINATION BY XIAP.
RX PubMed=29020630; DOI=10.1016/j.celrep.2017.09.052;
RA Edison N., Curtz Y., Paland N., Mamriev D., Chorubczyk N.,
RA Haviv-Reingewertz T., Kfir N., Morgenstern D., Kupervaser M., Kagan J.,
RA Kim H.T., Larisch S.;
RT "Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis.";
RL Cell Rep. 21:442-454(2017).
RN [36]
RP INTERACTION WITH BCAP31.
RX PubMed=31206022; DOI=10.1126/sciadv.aaw1386;
RA Namba T.;
RT "BAP31 regulates mitochondrial function via interaction with Tom40 within
RT ER-mitochondria contact sites.";
RL Sci. Adv. 5:eaaw1386-eaaw1386(2019).
RN [37]
RP STRUCTURE BY NMR OF 1-207.
RX PubMed=11248023; DOI=10.1073/pnas.041619798;
RA Petros A.M., Medek A., Nettesheim D.G., Kim D.H., Yoon H.S., Swift K.,
RA Matayoshi E.D., Oltersdorf T., Fesik S.W.;
RT "Solution structure of the antiapoptotic protein bcl-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3012-3017(2001).
RN [38]
RP STRUCTURE BY NMR OF 45-207.
RX PubMed=15902208; DOI=10.1038/nature03579;
RA Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C., Augeri D.J.,
RA Belli B.A., Bruncko M., Deckwerth T.L., Dinges J., Hajduk P.J.,
RA Joseph M.K., Kitada S., Korsmeyer S.J., Kunzer A.R., Letai A., Li C.,
RA Mitten M.J., Nettesheim D.G., Ng S.-C., Nimmer P.M., O'Connor J.M.,
RA Oleksijew A., Petros A.M., Reed J.C., Shen W., Tahir S.K., Thompson C.B.,
RA Tomaselli K.J., Wang B., Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H.;
RT "An inhibitor of Bcl-2 family proteins induces regression of solid
RT tumours.";
RL Nature 435:677-681(2005).
RN [39]
RP STRUCTURE BY NMR OF 44-207.
RX PubMed=17256834; DOI=10.1021/jm061152t;
RA Bruncko M., Oost T.K., Belli B.A., Ding H., Joseph M.K., Kunzer A.,
RA Martineau D., McClellan W.J., Mitten M., Ng S.-C., Nimmer P.M.,
RA Oltersdorf T., Park C.-M., Petros A.M., Shoemaker A.R., Song X., Wang X.,
RA Wendt M.D., Zhang H., Fesik S.W., Rosenberg S.H., Elmore S.W.;
RT "Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.";
RL J. Med. Chem. 50:641-662(2007).
CC -!- FUNCTION: Suppresses apoptosis in a variety of cell systems including
CC factor-dependent lymphohematopoietic and neural cells (PubMed:1508712,
CC PubMed:8183370). Regulates cell death by controlling the mitochondrial
CC membrane permeability (PubMed:11368354). Appears to function in a
CC feedback loop system with caspases (PubMed:11368354). Inhibits caspase
CC activity either by preventing the release of cytochrome c from the
CC mitochondria and/or by binding to the apoptosis-activating factor
CC (APAF-1) (PubMed:11368354). Also acts as an inhibitor of autophagy:
CC interacts with BECN1 and AMBRA1 during non-starvation conditions and
CC inhibits their autophagy function (PubMed:18570871, PubMed:21358617,
CC PubMed:20889974). May attenuate inflammation by impairing NLRP1-
CC inflammasome activation, hence CASP1 activation and IL1B release
CC (PubMed:17418785). {ECO:0000269|PubMed:1508712,
CC ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18570871,
CC ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21358617,
CC ECO:0000269|PubMed:8183370, ECO:0000303|PubMed:11368354}.
CC -!- SUBUNIT: Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-
CC X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs,
CC and is necessary for anti-apoptotic activity (PubMed:8183370,
CC PubMed:25609812). Part of a complex composed of SEPTIN4 isoform ARTS,
CC XIAP and BCL2, within the complex interacts (via BH3 domain) with
CC SEPTIN4 isoform ARTS and XIAP, SEPTIN4 isoform ARTS acts as a scaffold
CC protein and stabilizes the complex (PubMed:29020630). Interacts with
CC EI24 (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL,
CC MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the
CC mitochondria and probably interferes with the binding of BCL2 to its
CC targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with
CC RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via
CC the BH4 domain) with EGLN3; the interaction prevents the formation of
CC the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2.
CC Interacts with G0S2; this interaction also prevents the formation of
CC the anti-apoptotic BAX-BCL2 complex. Interacts with RTL10/BOP.
CC Interacts with the SCF(FBXO10) complex. Interacts (via the loop between
CC motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2,
CC NLRP3, NLRP4, PYCARD, nor MEFV (PubMed:17418785). Interacts with
CC GIMAP3/IAN4, GIMAP4/IAN1 and GIMAP5/IAN5 (By similarity). Interacts
CC with BCAP31 (PubMed:31206022). Interacts with IRF3; the interaction is
CC inhibited by Sendai virus infection (PubMed:25609812). Interacts with
CC BECN1; thereby inhibiting autophagy in non-starvation conditions
CC (PubMed:18570871, PubMed:21358617). Interacts with AMBRA1; thereby
CC inhibiting autophagy (PubMed:21358617). {ECO:0000250|UniProtKB:P10417,
CC ECO:0000269|PubMed:11463391, ECO:0000269|PubMed:12901880,
CC ECO:0000269|PubMed:15547950, ECO:0000269|PubMed:15733859,
CC ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:17090549,
CC ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18570871,
CC ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:19706769,
CC ECO:0000269|PubMed:20849813, ECO:0000269|PubMed:21358617,
CC ECO:0000269|PubMed:23055042, ECO:0000269|PubMed:23431138,
CC ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:29020630,
CC ECO:0000269|PubMed:31206022, ECO:0000269|PubMed:8183370,
CC ECO:0000269|PubMed:8668206, ECO:0000269|PubMed:9305631}.
CC -!- INTERACTION:
CC P10415; Q9C0C7: AMBRA1; NbExp=10; IntAct=EBI-77694, EBI-2512975;
CC P10415; P05067: APP; NbExp=3; IntAct=EBI-77694, EBI-77613;
CC P10415; Q92934: BAD; NbExp=5; IntAct=EBI-77694, EBI-700771;
CC P10415; Q16611: BAK1; NbExp=3; IntAct=EBI-77694, EBI-519866;
CC P10415; Q07812: BAX; NbExp=14; IntAct=EBI-77694, EBI-516580;
CC P10415; Q9BXH1: BBC3; NbExp=6; IntAct=EBI-77694, EBI-519884;
CC P10415; P51572: BCAP31; NbExp=2; IntAct=EBI-77694, EBI-77683;
CC P10415; P10415: BCL2; NbExp=3; IntAct=EBI-77694, EBI-77694;
CC P10415; O43521: BCL2L11; NbExp=8; IntAct=EBI-77694, EBI-526406;
CC P10415; O43521-1: BCL2L11; NbExp=3; IntAct=EBI-77694, EBI-526416;
CC P10415; O43521-2: BCL2L11; NbExp=4; IntAct=EBI-77694, EBI-526420;
CC P10415; Q9NYF8: BCLAF1; NbExp=2; IntAct=EBI-77694, EBI-437804;
CC P10415; Q14457: BECN1; NbExp=18; IntAct=EBI-77694, EBI-949378;
CC P10415; P55957: BID; NbExp=9; IntAct=EBI-77694, EBI-519672;
CC P10415; Q13323: BIK; NbExp=6; IntAct=EBI-77694, EBI-700794;
CC P10415; O60238: BNIP3L; NbExp=2; IntAct=EBI-77694, EBI-849893;
CC P10415; Q8N5K1: CISD2; NbExp=2; IntAct=EBI-77694, EBI-1045797;
CC P10415; O15151: MDM4; NbExp=4; IntAct=EBI-77694, EBI-398437;
CC P10415; Q9C000: NLRP1; NbExp=13; IntAct=EBI-77694, EBI-1220518;
CC P10415; P22736: NR4A1; NbExp=7; IntAct=EBI-77694, EBI-721550;
CC P10415; Q13794: PMAIP1; NbExp=3; IntAct=EBI-77694, EBI-707392;
CC P10415; O15304: SIVA1; NbExp=2; IntAct=EBI-77694, EBI-520756;
CC P10415; P00441: SOD1; NbExp=3; IntAct=EBI-77694, EBI-990792;
CC P10415; P04637: TP53; NbExp=5; IntAct=EBI-77694, EBI-366083;
CC P10415; Q13625: TP53BP2; NbExp=10; IntAct=EBI-77694, EBI-77642;
CC P10415; Q61337: Bad; Xeno; NbExp=6; IntAct=EBI-77694, EBI-400328;
CC P10415; Q91ZE9: Bmf; Xeno; NbExp=2; IntAct=EBI-77694, EBI-708032;
CC P10415; P11881: Itpr1; Xeno; NbExp=3; IntAct=EBI-77694, EBI-541478;
CC P10415-1; Q5S007: LRRK2; NbExp=2; IntAct=EBI-4370304, EBI-5323863;
CC P10415-1; Q13794: PMAIP1; NbExp=3; IntAct=EBI-4370304, EBI-707392;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:21358617, ECO:0000269|PubMed:2250705}; Single-pass
CC membrane protein {ECO:0000255}. Nucleus membrane
CC {ECO:0000269|PubMed:2250705}; Single-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21358617, ECO:0000269|PubMed:2250705}; Single-pass
CC membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P10417}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=P10415-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=P10415-2; Sequence=VSP_000512;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC -!- DOMAIN: BH1 and BH2 domains are required for the interaction with BAX
CC and for anti-apoptotic activity. {ECO:0000269|PubMed:8183370}.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and for
CC interaction with RAF1 and EGLN3.
CC -!- DOMAIN: The loop between motifs BH4 and BH3 is required for the
CC interaction with NLRP1. {ECO:0000269|PubMed:17418785}.
CC -!- DOMAIN: The BH3 domain is required for interaction with SEPTIN4 isoform
CC ARTS and thereby for XIAP-mediated ubiquitination and subsequent
CC induction of apoptosis. {ECO:0000269|PubMed:29020630}.
CC -!- PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti-
CC apoptotic activity (PubMed:11368354). Growth factor-stimulated
CC phosphorylation on Ser-70 by PKC is required for the anti-apoptosis
CC activity and occurs during the G2/M phase of the cell cycle
CC (PubMed:11368354). In the absence of growth factors, BCL2 appears to be
CC phosphorylated by other protein kinases such as ERKs and stress-
CC activated kinases (PubMed:11368354). Phosphorylated by MAPK8/JNK1 at
CC Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophag
CC (PubMed:10567572, PubMed:18570871). Dephosphorylated by protein
CC phosphatase 2A (PP2A) (By similarity). {ECO:0000250|UniProtKB:P10417,
CC ECO:0000269|PubMed:10567572, ECO:0000269|PubMed:18570871,
CC ECO:0000303|PubMed:11368354}.
CC -!- PTM: Proteolytically cleaved by caspases during apoptosis. The cleaved
CC protein, lacking the BH4 motif, has pro-apoptotic activity, causes the
CC release of cytochrome c into the cytosol promoting further caspase
CC activity. {ECO:0000269|PubMed:9395403}.
CC -!- PTM: Monoubiquitinated by PRKN, leading to an increase in its stability
CC (PubMed:20889974). Ubiquitinated by SCF(FBXO10), leading to its
CC degradation by the proteasome (PubMed:23431138). Ubiquitinated by XIAP,
CC leading to its degradation by the proteasome (PubMed:29020630).
CC {ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:23431138,
CC ECO:0000269|PubMed:29020630}.
CC -!- DISEASE: Note=A chromosomal aberration involving BCL2 has been found in
CC chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with
CC immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin
CC lymphomas carrying the chromosomal translocation could be attributed to
CC the Ig somatic hypermutation mechanism resulting in nucleotide
CC transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BCL2ID49.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/bcl2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bcl-2 entry;
CC URL="https://en.wikipedia.org/wiki/Bcl-2";
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DR EMBL; M13994; AAA51813.1; ALT_SEQ; mRNA.
DR EMBL; M13995; AAA51814.1; ALT_SEQ; mRNA.
DR EMBL; M14745; AAA35591.1; -; mRNA.
DR EMBL; X06487; CAA29778.1; -; mRNA.
DR EMBL; AY220759; AAO26045.1; -; Genomic_DNA.
DR EMBL; AC021803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC022726; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW63137.1; -; Genomic_DNA.
DR EMBL; BC027258; AAH27258.1; -; mRNA.
DR EMBL; S72602; AAD14111.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS11981.1; -. [P10415-1]
DR CCDS; CCDS45882.1; -. [P10415-2]
DR PIR; B29409; TVHUB1.
DR PIR; C37332; TVHUA1.
DR RefSeq; NP_000624.2; NM_000633.2. [P10415-1]
DR RefSeq; NP_000648.2; NM_000657.2. [P10415-2]
DR PDB; 1G5M; NMR; -; A=1-34, A=92-207.
DR PDB; 1GJH; NMR; -; A=1-34, A=92-207.
DR PDB; 1YSW; NMR; -; A=3-33, A=92-206.
DR PDB; 2O21; NMR; -; A=3-34, A=92-207.
DR PDB; 2O22; NMR; -; A=3-34, A=92-207.
DR PDB; 2O2F; NMR; -; A=8-31, A=92-204.
DR PDB; 2W3L; X-ray; 2.10 A; A/B=92-206.
DR PDB; 2XA0; X-ray; 2.70 A; A/B=1-207.
DR PDB; 4AQ3; X-ray; 2.40 A; A/B/C/D/E/F=1-33, A/B/C/D/E/F=92-207.
DR PDB; 4IEH; X-ray; 2.10 A; A=1-34, A=92-207.
DR PDB; 4LVT; X-ray; 2.05 A; A/B=1-34, A/B=92-207.
DR PDB; 4LXD; X-ray; 1.90 A; A=1-34, A=92-207.
DR PDB; 4MAN; X-ray; 2.07 A; A/B=1-34, A/B=92-207.
DR PDB; 5AGW; X-ray; 2.69 A; A/B=1-34, A/B=92-207.
DR PDB; 5AGX; X-ray; 2.24 A; A/B=1-34, A/B=92-207.
DR PDB; 5FCG; X-ray; 2.10 A; A=1-207.
DR PDB; 5JSN; X-ray; 2.10 A; A/C=1-207.
DR PDB; 5VAU; X-ray; 1.75 A; A/B/C/D=1-207.
DR PDB; 5VAX; X-ray; 2.00 A; A/B/C/D=1-207.
DR PDB; 5VAY; X-ray; 1.80 A; A/B/C/D=1-34, A/B/C/D=66-207.
DR PDB; 6GL8; X-ray; 1.40 A; A=9-206.
DR PDB; 6IWB; X-ray; 2.50 A; B/D=1-34, B/D=92-207.
DR PDB; 6O0K; X-ray; 1.62 A; A=1-34, A=66-207.
DR PDB; 6O0L; X-ray; 2.20 A; A/C=1-34, A/C=66-207.
DR PDB; 6O0M; X-ray; 1.75 A; A=1-34, A=66-207.
DR PDB; 6O0O; X-ray; 2.00 A; A/C=1-34, A/C=66-207.
DR PDB; 6O0P; X-ray; 1.80 A; A=1-34, A=66-207.
DR PDB; 7LHB; X-ray; 2.07 A; A/B/C=1-207.
DR PDBsum; 1G5M; -.
DR PDBsum; 1GJH; -.
DR PDBsum; 1YSW; -.
DR PDBsum; 2O21; -.
DR PDBsum; 2O22; -.
DR PDBsum; 2O2F; -.
DR PDBsum; 2W3L; -.
DR PDBsum; 2XA0; -.
DR PDBsum; 4AQ3; -.
DR PDBsum; 4IEH; -.
DR PDBsum; 4LVT; -.
DR PDBsum; 4LXD; -.
DR PDBsum; 4MAN; -.
DR PDBsum; 5AGW; -.
DR PDBsum; 5AGX; -.
DR PDBsum; 5FCG; -.
DR PDBsum; 5JSN; -.
DR PDBsum; 5VAU; -.
DR PDBsum; 5VAX; -.
DR PDBsum; 5VAY; -.
DR PDBsum; 6GL8; -.
DR PDBsum; 6IWB; -.
DR PDBsum; 6O0K; -.
DR PDBsum; 6O0L; -.
DR PDBsum; 6O0M; -.
DR PDBsum; 6O0O; -.
DR PDBsum; 6O0P; -.
DR PDBsum; 7LHB; -.
DR AlphaFoldDB; P10415; -.
DR SMR; P10415; -.
DR BioGRID; 107068; 141.
DR ComplexPortal; CPX-1981; BCL-2 dimer.
DR ComplexPortal; CPX-1982; BAD:BCL-2 complex.
DR ComplexPortal; CPX-1984; BID:BCL-2 complex.
DR ComplexPortal; CPX-1986; PUMA:BCL-2 complex.
DR ComplexPortal; CPX-1990; BIM:BCL-2 complex.
DR CORUM; P10415; -.
DR DIP; DIP-1043N; -.
DR ELM; P10415; -.
DR IntAct; P10415; 55.
DR MINT; P10415; -.
DR STRING; 9606.ENSP00000381185; -.
DR BindingDB; P10415; -.
DR ChEMBL; CHEMBL4860; -.
DR DrugBank; DB06307; Apoptone.
DR DrugBank; DB06756; Betaine.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB08871; Eribulin.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB12340; Navitoclax.
DR DrugBank; DB12191; Obatoclax.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB05297; Paclitaxel docosahexaenoic acid.
DR DrugBank; DB01367; Rasagiline.
DR DrugBank; DB11581; Venetoclax.
DR DrugCentral; P10415; -.
DR GuidetoPHARMACOLOGY; 2844; -.
DR TCDB; 1.A.21.1.10; the bcl-2 (bcl-2) family.
DR iPTMnet; P10415; -.
DR PhosphoSitePlus; P10415; -.
DR BioMuta; BCL2; -.
DR DMDM; 231632; -.
DR EPD; P10415; -.
DR jPOST; P10415; -.
DR MassIVE; P10415; -.
DR MaxQB; P10415; -.
DR PaxDb; P10415; -.
DR PeptideAtlas; P10415; -.
DR PRIDE; P10415; -.
DR ProteomicsDB; 10203; -.
DR ProteomicsDB; 52603; -. [P10415-1]
DR ProteomicsDB; 52604; -. [P10415-2]
DR ABCD; P10415; 1 sequenced antibody.
DR Antibodypedia; 3491; 3923 antibodies from 60 providers.
DR DNASU; 596; -.
DR Ensembl; ENST00000333681.5; ENSP00000329623.3; ENSG00000171791.14. [P10415-1]
DR Ensembl; ENST00000398117.1; ENSP00000381185.1; ENSG00000171791.14. [P10415-1]
DR Ensembl; ENST00000589955.2; ENSP00000466417.1; ENSG00000171791.14. [P10415-2]
DR Ensembl; ENST00000678349.1; ENSP00000504190.1; ENSG00000171791.14. [P10415-2]
DR GeneID; 596; -.
DR KEGG; hsa:596; -.
DR MANE-Select; ENST00000333681.5; ENSP00000329623.3; NM_000633.3; NP_000624.2.
DR UCSC; uc002lit.2; human. [P10415-1]
DR CTD; 596; -.
DR DisGeNET; 596; -.
DR GeneCards; BCL2; -.
DR HGNC; HGNC:990; BCL2.
DR HPA; ENSG00000171791; Low tissue specificity.
DR MalaCards; BCL2; -.
DR MIM; 151430; gene+phenotype.
DR neXtProt; NX_P10415; -.
DR OpenTargets; ENSG00000171791; -.
DR Orphanet; 545; Follicular lymphoma.
DR Orphanet; 480541; High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement.
DR Orphanet; 98839; Intravascular large B-cell lymphoma.
DR PharmGKB; PA25302; -.
DR VEuPathDB; HostDB:ENSG00000171791; -.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244953; -.
DR HOGENOM; CLU_085401_0_0_1; -.
DR InParanoid; P10415; -.
DR OMA; QRGYDWA; -.
DR OrthoDB; 80538at2759; -.
DR PhylomeDB; P10415; -.
DR TreeFam; TF315834; -.
DR PathwayCommons; P10415; -.
DR Reactome; R-HSA-111447; Activation of BAD and translocation to mitochondria.
DR Reactome; R-HSA-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-844455; The NLRP1 inflammasome.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; P10415; -.
DR SIGNOR; P10415; -.
DR BioGRID-ORCS; 596; 61 hits in 1079 CRISPR screens.
DR ChiTaRS; BCL2; human.
DR EvolutionaryTrace; P10415; -.
DR GeneWiki; Bcl-2; -.
DR GenomeRNAi; 596; -.
DR Pharos; P10415; Tclin.
DR PRO; PR:P10415; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P10415; protein.
DR Bgee; ENSG00000171791; Expressed in dorsal motor nucleus of vagus nerve and 205 other tissues.
DR ExpressionAtlas; P10415; baseline and differential.
DR Genevisible; P10415; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0046930; C:pore complex; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0051434; F:BH3 domain binding; IPI:UniProtKB.
DR GO; GO:0015267; F:channel activity; IDA:BHF-UCL.
DR GO; GO:0016248; F:channel inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0002020; F:protease binding; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0002326; P:B cell lineage commitment; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; IDA:MGI.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl.
DR GO; GO:0060402; P:calcium ion transport into cytosol; IEA:Ensembl.
DR GO; GO:0043375; P:CD8-positive, alpha-beta T cell lineage commitment; IEA:Ensembl.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0021747; P:cochlear nucleus development; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR GO; GO:0097048; P:dendritic cell apoptotic process; IEA:Ensembl.
DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0043583; P:ear development; IEA:Ensembl.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; TAS:UniProtKB.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:MGI.
DR GO; GO:0007565; P:female pregnancy; NAS:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0022612; P:gland morphogenesis; IEA:Ensembl.
DR GO; GO:0032835; P:glomerulus development; IEA:Ensembl.
DR GO; GO:0031069; P:hair follicle morphogenesis; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0006959; P:humoral immune response; TAS:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:MGI.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0006582; P:melanin metabolic process; IEA:Ensembl.
DR GO; GO:0030318; P:melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0014031; P:mesenchymal cell development; IEA:Ensembl.
DR GO; GO:0001656; P:metanephros development; IEA:Ensembl.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:2000811; P:negative regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl.
DR GO; GO:0032848; P:negative regulation of cellular pH reduction; IDA:UniProtKB.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IEA:Ensembl.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IGI:MGI.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; TAS:BHF-UCL.
DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; TAS:UniProtKB.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0046671; P:negative regulation of retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; TAS:HGNC-UCL.
DR GO; GO:0042551; P:neuron maturation; IEA:Ensembl.
DR GO; GO:0048599; P:oocyte development; IEA:Ensembl.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IEA:Ensembl.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0048753; P:pigment granule organization; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:ARUK-UCL.
DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0014042; P:positive regulation of neuron maturation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0048743; P:positive regulation of skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:MGI.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010559; P:regulation of glycoprotein biosynthetic process; IEA:Ensembl.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:HGNC-UCL.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISS:HGNC-UCL.
DR GO; GO:0006808; P:regulation of nitrogen utilization; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0045069; P:regulation of viral genome replication; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:HGNC-UCL.
DR GO; GO:0003014; P:renal system process; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IDA:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0010039; P:response to iron ion; IDA:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1904373; P:response to kainic acid; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IDA:UniProtKB.
DR GO; GO:0009314; P:response to radiation; NAS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IDA:HGNC-UCL.
DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0046666; P:retinal cell programmed cell death; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0014909; P:smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR GO; GO:0048864; P:stem cell development; IEA:Ensembl.
DR GO; GO:0070231; P:T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0043029; P:T cell homeostasis; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR CDD; cd06845; Bcl-2_like; 1.
DR DisProt; DP00297; -.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013278; Apop_reg_Bcl2.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR004725; Bcl2/BclX.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF11; PTHR11256:SF11; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01863; APOPREGBCL2.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SMART; SM00265; BH4; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR TIGRFAMs; TIGR00865; bcl-2; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Chromosomal rearrangement;
KW Cytoplasm; Disease variant; Endoplasmic reticulum; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..239
FT /note="Apoptosis regulator Bcl-2"
FT /id="PRO_0000143048"
FT TRANSMEM 212..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 39..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..107
FT /note="Required for interaction with SEPTIN4 isoform ARTS.
FT Required XIAP-mediated ubiquitination and apoptosis"
FT /evidence="ECO:0000269|PubMed:29020630"
FT MOTIF 10..30
FT /note="BH4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00025"
FT MOTIF 93..107
FT /note="BH3"
FT /evidence="ECO:0000255"
FT MOTIF 136..155
FT /note="BH1"
FT /evidence="ECO:0000255"
FT MOTIF 187..202
FT /note="BH2"
FT /evidence="ECO:0000255"
FT SITE 34..35
FT /note="Cleavage; by caspase-3"
FT MOD_RES 69
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:18570871"
FT MOD_RES 70
FT /note="Phosphoserine; by MAPK8 and PKC"
FT /evidence="ECO:0000269|PubMed:18570871"
FT MOD_RES 87
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:18570871"
FT VAR_SEQ 196..239
FT /note="DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK -> VGAL
FT GDVSLG (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:3523487"
FT /id="VSP_000512"
FT VARIANT 7
FT /note="T -> S"
FT /evidence="ECO:0000269|PubMed:2834197,
FT ECO:0000269|PubMed:3285301"
FT /id="VAR_000827"
FT VARIANT 43
FT /note="A -> T (in dbSNP:rs1800477)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_014716"
FT VARIANT 59
FT /note="P -> S (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:1339299"
FT /id="VAR_000828"
FT VARIANT 93
FT /note="V -> I (in non-Hodgkin lymphoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:1339299"
FT /id="VAR_000829"
FT MUTAGEN 34
FT /note="D->A: Abolishes cleavage by caspase-3."
FT /evidence="ECO:0000269|PubMed:9395403"
FT MUTAGEN 64
FT /note="D->A: No effect on cleavage by caspase-3."
FT /evidence="ECO:0000269|PubMed:9395403"
FT MUTAGEN 138..141
FT /note="FRDG->AAAA: Loss of BAX-binding and of anti-
FT apoptotic activity."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 144
FT /note="W->A: Loss of BAX-binding and of anti-apoptotic
FT activity; when associated with A-145 and A146."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 145
FT /note="G->A: Loss of BAX-binding and of anti-apoptotic
FT activity. No effect on NLRP1-induced IL1B release, nor on
FT homodimerization. Loss of BAX-binding and of anti-apoptotic
FT activity; when associated with A-145 and A146."
FT /evidence="ECO:0000269|PubMed:17418785,
FT ECO:0000269|PubMed:8183370"
FT MUTAGEN 145
FT /note="G->E: Loss of BAX-binding and of anti-apoptotic
FT activity. No effect on homodimerization."
FT /evidence="ECO:0000269|PubMed:17418785,
FT ECO:0000269|PubMed:8183370"
FT MUTAGEN 146
FT /note="R->A: Loss of BAX-binding and of anti-apoptotic
FT activity; when associated with A-144 and A145."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 188
FT /note="W->A: Loss of BAX-binding and of anti-apoptotic
FT activity. No effect on homodimerization."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 190
FT /note="Q->L: Partial loss of BAX-binding and 50% decrease
FT in anti-apoptotic activity; when associated with A-191 and
FT A-192. No effect on homodimerization; when associated with
FT L-190 and A-191."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 191
FT /note="D->A: No effect on BAX-binding, nor on anti-
FT apoptotic activity. Partial loss of BAX-binding and 50%
FT decrease in anti-apoptotic activity; when associated with
FT L-190 and A-192. No effect on homodimerization; when
FT associated with L-190 and A-191."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 192
FT /note="N->A: Partial loss of BAX-binding and 50% decrease
FT in anti-apoptotic activity; when associated with L-190 and
FT A-191. No effect on homodimerization; when associated with
FT L-190 and A-191."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 194..197
FT /note="Missing: Loss of BAX-binding and of anti-apoptotic
FT activity. May also affect protein stability."
FT /evidence="ECO:0000269|PubMed:8183370"
FT MUTAGEN 200
FT /note="E->A: Partial loss of BAX-binding and 50% decrease
FT in anti-apoptotic activity."
FT /evidence="ECO:0000269|PubMed:8183370"
FT CONFLICT 48
FT /note="I -> F (in Ref. 4; CAA29778)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="P -> T (in Ref. 3; AAA35591)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="T -> A (in Ref. 10; AAD14111)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="R -> G (in Ref. 10; AAD14111)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="S -> R (in Ref. 3; AAA35591)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="R -> C (in Ref. 4; CAA29778)"
FT /evidence="ECO:0000305"
FT HELIX 11..25
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:5VAX"
FT HELIX 93..98
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 103..107
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:6GL8"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 144..163
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 169..184
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 194..202
FT /evidence="ECO:0007829|PDB:6GL8"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:5VAX"
FT CONFLICT P10415-2:199
FT /note="L -> S (in Ref. 1; AAA51814)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 239 AA; 26266 MW; 3C49F2B714DC9CCB CRC64;
MAHAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDVGAAPP GAAPAPGIFS SQPGHTPHPA
ASRDPVARTS PLQTPAAPGA AAGPALSPVP PVVHLTLRQA GDDFSRRYRR DFAEMSSQLH
LTPFTARGRF ATVVEELFRD GVNWGRIVAF FEFGGVMCVE SVNREMSPLV DNIALWMTEY
LNRHLHTWIQ DNGGWDAFVE LYGPSMRPLF DFSWLSLKTL LSLALVGACI TLGAYLGHK
