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Database: UniProt
Entry: P10415
LinkDB: P10415
Original site: P10415 
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   07-APR-2021, entry version 255.
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.
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   INTERACTION WITH BAX, HOMODIMERIZATION, SUBUNIT, AND MUTAGENESIS OF
RP   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.
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, 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   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   [30]
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   [31]
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   [32]
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   [33]
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   [34]
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   [35]
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   [36]
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   [37]
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. Regulates cell
CC       death by controlling the mitochondrial membrane permeability. Appears
CC       to function in a feedback loop system with caspases. 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). May attenuate inflammation by impairing NLRP1-inflammasome
CC       activation, hence CASP1 activation and IL1B release (PubMed:17418785).
CC       {ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18570871}.
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). Interacts with EI24 (By similarity). Also interacts
CC       with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8
CC       seems to target BCL2 to the mitochondria and probably interferes with
CC       the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-
CC       dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339'
CC       phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the
CC       interaction prevents the formation of the BAX-BCL2 complex and inhibits
CC       the anti-apoptotic activity of BCL2. Interacts with G0S2; this
CC       interaction also prevents the formation of the anti-apoptotic BAX-BCL2
CC       complex. Interacts with RTL10/BOP. Interacts with the SCF(FBXO10)
CC       complex. Interacts (via the loop between motifs BH4 and BH3) with NLRP1
CC       (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV
CC       (PubMed:17418785). Interacts with GIMAP3/IAN4, GIMAP4/IAN1 and
CC       GIMAP5/IAN5 (By similarity). Interacts with BCAP31 (PubMed:31206022).
CC       Interacts with IRF3; the interaction is inhibited by Sendai virus
CC       infection (PubMed:25609812). {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:19228691,
CC       ECO:0000269|PubMed:19706769, ECO:0000269|PubMed:20849813,
CC       ECO:0000269|PubMed:23055042, ECO:0000269|PubMed:23431138,
CC       ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:31206022,
CC       ECO:0000269|PubMed:8183370, ECO:0000269|PubMed:8668206,
CC       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=13; 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:2250705}; Single-pass membrane protein
CC       {ECO:0000269|PubMed:2250705}. Nucleus membrane
CC       {ECO:0000269|PubMed:2250705}; Single-pass membrane protein
CC       {ECO:0000269|PubMed:2250705}. Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:2250705}; Single-pass membrane protein
CC       {ECO:0000269|PubMed:2250705}.
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   -!- PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti-
CC       apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70
CC       by PKC is required for the anti-apoptosis activity and occurs during
CC       the G2/M phase of the cell cycle. In the absence of growth factors,
CC       BCL2 appears to be phosphorylated by other protein kinases such as ERKs
CC       and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69,
CC       Ser-70 and Ser-87, wich stimulates starvation-induced autophagy.
CC       Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity).
CC       {ECO:0000250}.
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 increase its stability.
CC       Ubiquitinated by SCF(FBXO10), leading to its degradation by the
CC       proteasome. {ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:23431138}.
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   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   SMR; P10415; -.
DR   BioGRID; 107068; 116.
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; 54.
DR   MINT; P10415; -.
DR   STRING; 9606.ENSP00000381185; -.
DR   BindingDB; P10415; -.
DR   ChEMBL; CHEMBL4860; -.
DR   DrugBank; DB06307; Apoptone.
DR   DrugBank; DB09213; Dexibuprofen.
DR   DrugBank; DB01248; Docetaxel.
DR   DrugBank; DB08871; Eribulin.
DR   DrugBank; DB06756; Glycine betaine.
DR   DrugBank; DB01050; Ibuprofen.
DR   DrugBank; DB09401; Isosorbide.
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; 3783 antibodies.
DR   DNASU; 596; -.
DR   Ensembl; ENST00000333681; ENSP00000329623; ENSG00000171791. [P10415-1]
DR   Ensembl; ENST00000398117; ENSP00000381185; ENSG00000171791. [P10415-1]
DR   Ensembl; ENST00000589955; ENSP00000466417; ENSG00000171791. [P10415-2]
DR   Ensembl; ENST00000678349; ENSP00000504190; ENSG00000171791. [P10415-2]
DR   GeneID; 596; -.
DR   KEGG; hsa:596; -.
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:ENSG00000171791.12; -.
DR   eggNOG; KOG4728; Eukaryota.
DR   GeneTree; ENSGT01020000230347; -.
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   SIGNOR; P10415; -.
DR   BioGRID-ORCS; 596; 57 hits in 996 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 thyroid gland and 238 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; IEA:UniProtKB-SubCell.
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: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:0070491; F:repressing transcription factor binding; IPI:ARUK-UCL.
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: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:0043375; P:CD8-positive, alpha-beta T cell lineage commitment; IEA:Ensembl.
DR   GO; GO:0007569; P:cell aging; 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:0021747; P:cochlear nucleus development; IEA:Ensembl.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
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: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: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: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: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; TAS:UniProtKB.
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: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: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:0051402; P:neuron apoptotic process; TAS:HGNC-UCL.
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: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:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
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:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
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: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:0042493; P:response to drug; 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:0048536; P:spleen development; 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   InterPro; IPR013278; Apop_reg_Bcl2.
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   InterPro; IPR036834; Blc2-like_sf.
DR   InterPro; IPR026298; Blc2_fam.
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   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   MOTIF           10..30
FT                   /note="BH4"
FT   MOTIF           93..107
FT                   /note="BH3"
FT   MOTIF           136..155
FT                   /note="BH1"
FT   MOTIF           187..202
FT                   /note="BH2"
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   MUTAGEN         64
FT                   /note="D->A: No effect on cleavage by caspase-3."
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:0007744|PDB:6GL8"
FT   HELIX           31..33
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           63..66
FT                   /evidence="ECO:0007744|PDB:5VAX"
FT   HELIX           93..98
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           103..107
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           109..119
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   TURN            123..125
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           126..138
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           144..163
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           169..184
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           186..191
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           194..202
FT                   /evidence="ECO:0007744|PDB:6GL8"
FT   HELIX           203..205
FT                   /evidence="ECO:0007744|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
//
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