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 27-MAR-2024, entry version 269. 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, which 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="https://atlasgeneticsoncology.org/gene/49/BCL2"; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7Y90; X-ray; 2.09 A; A=1-34, A=92-207. DR PDB; 7YA5; X-ray; 1.85 A; A=1-34, A=92-207. DR PDB; 8HLL; X-ray; 2.62 A; B=10-35, B=92-203. DR PDB; 8HLM; X-ray; 2.52 A; B=10-35, B=92-203. DR PDB; 8HLN; X-ray; 2.35 A; B=10-35, B=92-203. DR PDB; 8U27; NMR; -; A=1-34, A=66-218. 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 PDBsum; 7Y90; -. DR PDBsum; 7YA5; -. DR PDBsum; 8HLL; -. DR PDBsum; 8HLM; -. DR PDBsum; 8HLN; -. DR PDBsum; 8U27; -. 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; 57. DR MINT; P10415; -. DR STRING; 9606.ENSP00000381185; -. DR BindingDB; P10415; -. DR ChEMBL; CHEMBL4860; -. DR DrugBank; DB05103; AN-9. DR DrugBank; DB06307; Apoptone. 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; DB12843; Oleandrin. DR DrugBank; DB01229; Paclitaxel. DR DrugBank; DB05297; Paclitaxel docosahexaenoic acid. DR DrugBank; DB01367; Rasagiline. DR DrugBank; DB12816; Terpinen-4-ol. 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; 9606-ENSP00000381185; -. DR PeptideAtlas; P10415; -. DR ProteomicsDB; 10203; -. DR ProteomicsDB; 52603; -. [P10415-1] DR ProteomicsDB; 52604; -. [P10415-2] DR Pumba; P10415; -. DR ABCD; P10415; 1 sequenced antibody. DR Antibodypedia; 3491; 4668 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 AGR; HGNC:990; -. 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; ENSGT01090000260003; -. DR HOGENOM; CLU_085401_0_0_1; -. DR InParanoid; P10415; -. DR OMA; CASKEEM; -. DR OrthoDB; 4028889at2759; -. 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 Reactome; R-HSA-9818030; NFE2L2 regulating tumorigenic genes. DR SignaLink; P10415; -. DR SIGNOR; P10415; -. DR BioGRID-ORCS; 596; 63 hits in 1162 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 206 other cell types or tissues. DR ExpressionAtlas; P10415; baseline and differential. DR GO; GO:0097138; C:BAD-BCL-2 complex; IPI:ComplexPortal. 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: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:0060090; F:molecular adaptor activity; EXP:DisProt. 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: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:0006974; P:DNA damage response; IMP:UniProtKB. 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:0051649; P:establishment of localization in cell; 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:0048753; P:pigment granule organization; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; NAS:ComplexPortal. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB. 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: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: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; Blc2-like; 1. DR IDEAL; IID00707; -. 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 NCBIfam; TIGR00865; bcl-2; 1. DR PANTHER; PTHR11256:SF11; APOPTOSIS REGULATOR BCL-2; 1. DR PANTHER; PTHR11256; BCL-2 RELATED; 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; Bcl-2 inhibitors of programmed cell death; 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. DR Genevisible; P10415; HS. 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 FT anti-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 FT anti-apoptotic activity. Partial loss of BAX-binding and FT 50% decrease in anti-apoptotic activity; when associated FT with 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 //