BCL2_MOUSE
ID BCL2_MOUSE Reviewed; 236 AA.
AC P10417; P10418; Q4VBF6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Apoptosis regulator Bcl-2;
GN Name=Bcl2; Synonyms=Bcl-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA AND BETA).
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=3032455; DOI=10.1016/0092-8674(87)90448-x;
RA Negrini M., Silini E., Kozak C., Tsujimoto Y., Croce C.M.;
RT "Molecular analysis of mbcl-2: structure and expression of the murine gene
RT homologous to the human gene involved in follicular lymphoma.";
RL Cell 49:455-463(1987).
RN [2]
RP SEQUENCE REVISION TO 221-222.
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [6]
RP PHOSPHORYLATION AT SER-70 BY PKC, AND MUTAGENESIS OF SER-70.
RX PubMed=9115213; DOI=10.1074/jbc.272.18.11671;
RA Ito T., Deng X., Carr B., May W.S. Jr.;
RT "Bcl-2 phosphorylation required for anti-apoptosis function.";
RL J. Biol. Chem. 272:11671-11673(1997).
RN [7]
RP DEPHOSPHORYLATION BY PP2A.
RX PubMed=9852076; DOI=10.1074/jbc.273.51.34157;
RA Deng X., Ito T., Carr B., Mumby M., May W.S. Jr.;
RT "Reversible phosphorylation of Bcl2 following interleukin 3 or bryostatin 1
RT is mediated by direct interaction with protein phosphatase 2A.";
RL J. Biol. Chem. 273:34157-34163(1998).
RN [8]
RP INTERACTION WITH EI24.
RX PubMed=15781622; DOI=10.1158/0008-5472.can-04-3377;
RA Zhao X., Ayer R.E., Davis S.L., Ames S.J., Florence B., Torchinsky C.,
RA Liou J.S., Shen L., Spanjaard R.A.;
RT "Apoptosis factor EI24/PIG8 is a novel endoplasmic reticulum-localized Bcl-
RT 2-binding protein which is associated with suppression of breast cancer
RT invasiveness.";
RL Cancer Res. 65:2125-2129(2005).
RN [9]
RP INTERACTION WITH GIMAP3; GIMAP4 AND GIMAP5.
RX PubMed=16509771; DOI=10.1371/journal.pbio.0040103;
RA Nitta T., Nasreen M., Seike T., Goji A., Ohigashi I., Miyazaki T., Ohta T.,
RA Kanno M., Takahama Y.;
RT "IAN family critically regulates survival and development of T
RT lymphocytes.";
RL PLoS Biol. 4:593-605(2006).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP INTERACTION WITH GIMAP5.
RX PubMed=21502331; DOI=10.1084/jem.20101192;
RA Chen Y., Yu M., Dai X., Zogg M., Wen R., Weiler H., Wang D.;
RT "Critical role for Gimap5 in the survival of mouse hematopoietic stem and
RT progenitor cells.";
RL J. Exp. Med. 208:923-935(2011).
RN [13]
RP SUBCELLULAR LOCATION.
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).
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). Also acts as an inhibitor of autophagy: interacts with BECN1
CC and AMBRA1 during non-starvation conditions and inhibits their
CC autophagy function (By similarity). May attenuate inflammation by
CC impairing NLRP1-inflammasome activation, hence CASP1 activation and
CC IL1B release (PubMed:17418785). {ECO:0000250|UniProtKB:P10415,
CC ECO:0000269|PubMed:17418785}.
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 (By similarity). Also
CC interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding
CC to FKBP8 seems to target BCL2 to the mitochondria and probably
CC interferes with the binding of BCL2 to its targets. Interacts with BAG1
CC in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and
CC 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with
CC EGLN3; the interaction prevents the formation of the BAX-BCL2 complex
CC and inhibits the anti-apoptotic activity of BCL2 (By similarity).
CC Interacts with EI24. Interacts with G0S2; this interaction also
CC prevents the formation of the anti-apoptotic BAX-BCL2 complex.
CC Interacts with PPIF; the interaction is impaired by CsA (By
CC similarity). Interacts with BOP (By similarity). Interacts with the
CC SCF(FBXO10) complex (By similarity). Interacts (via the loop between
CC motifs BH4 and BH3) with NLRP1 (via LRR repeats) (By similarity).
CC Interacts with GIMAP3/IAN4 and GIMAP4/IAN1 (PubMed:16509771). Also
CC interacts with GIMAP5/IAN5 (PubMed:16509771, PubMed:21502331).
CC Interacts with BCAP31 (By similarity). Interacts with IRF3 (By
CC similarity). Interacts with BECN1; thereby inhibiting autophagy in non-
CC starvation conditions (By similarity). Interacts with AMBRA1; thereby
CC inhibiting autophagy (By similarity). {ECO:0000250|UniProtKB:P10415,
CC ECO:0000269|PubMed:16509771, ECO:0000269|PubMed:21502331}.
CC -!- INTERACTION:
CC P10417; Q07813: Bax; NbExp=2; IntAct=EBI-526314, EBI-700711;
CC P10417; O54918-1: Bcl2l11; NbExp=2; IntAct=EBI-526314, EBI-526076;
CC P10417; O88597: Becn1; NbExp=11; IntAct=EBI-526314, EBI-643716;
CC P10417; Q99MI6: Gimap3; NbExp=4; IntAct=EBI-526314, EBI-15572304;
CC P10417; Q8BWF2: Gimap5; NbExp=3; IntAct=EBI-526314, EBI-15572348;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P10415}; Single-pass membrane protein
CC {ECO:0000255}. Nucleus membrane {ECO:0000250|UniProtKB:P10415}; Single-
CC pass membrane protein {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P10415}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:29020630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha;
CC IsoId=P10417-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=P10417-2; Sequence=VSP_000513;
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC -!- DOMAIN: The BH4 motif is required for anti-apoptotic activity and for
CC interaction with RAF1 and EGLN3.
CC -!- DOMAIN: BH1 and BH2 domains are required for the interaction with BAX
CC and for anti-apoptotic activity. {ECO:0000250|UniProtKB:P10415}.
CC -!- DOMAIN: The loop between motifs BH4 and BH3 is required for the
CC interaction with NLRP1. {ECO:0000250|UniProtKB:P10415}.
CC -!- DOMAIN: The BH3 motif is required for XIAP-mediated ubiquitination and
CC subsequent induction of apoptosis. {ECO:0000250|UniProtKB:P10415}.
CC -!- PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti-
CC apoptotic activity (PubMed:9115213). 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:9115213). 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:9115213). Phosphorylated by MAPK8/JNK1 at
CC Thr-69, Ser-70 and Ser-84, wich stimulates starvation-induced autophagy
CC (By similarity). Dephosphorylated by protein phosphatase 2A (PP2A)
CC (PubMed:9852076). {ECO:0000250|UniProtKB:P10415,
CC ECO:0000269|PubMed:9115213, ECO:0000269|PubMed:9852076}.
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:0000250|UniProtKB:P10415}.
CC -!- PTM: Monoubiquitinated by PRKN, leading to an increase in its stability
CC (By similarity). Ubiquitinated by SCF(FBXO10), leading to its
CC degradation by the proteasome (By similarity).
CC {ECO:0000250|UniProtKB:P10415}.
CC -!- DISRUPTION PHENOTYPE: In response to intraperitoneal injection of
CC muramyl dipeptide (MDP), knockout animals show lower serum IL1B levels
CC than wild type. Mutant macrophages release 30% less IL1B than the wild-
CC type cells. {ECO:0000269|PubMed:17418785}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; L31532; AAA37282.1; -; Genomic_DNA.
DR EMBL; M16506; AAA37282.1; JOINED; Genomic_DNA.
DR EMBL; M16506; AAA37281.1; -; Genomic_DNA.
DR EMBL; AC122842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC162916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466520; EDL39862.1; -; Genomic_DNA.
DR EMBL; BC095964; AAH95964.1; -; mRNA.
DR CCDS; CCDS15209.1; -. [P10417-1]
DR CCDS; CCDS78667.1; -. [P10417-2]
DR PIR; A25960; TVMSA1.
DR PIR; B25960; TVMSB1.
DR RefSeq; NP_033871.2; NM_009741.5. [P10417-1]
DR AlphaFoldDB; P10417; -.
DR SMR; P10417; -.
DR BioGRID; 198318; 33.
DR ComplexPortal; CPX-2017; BCL-2 dimer.
DR ComplexPortal; CPX-2019; BAD:BCL-2 complex.
DR ComplexPortal; CPX-2024; BID:BCL-2 complex.
DR ComplexPortal; CPX-2027; PUMA:BCL-2 complex.
DR ComplexPortal; CPX-2036; BIM:BCL-2 complex.
DR CORUM; P10417; -.
DR DIP; DIP-1065N; -.
DR IntAct; P10417; 10.
DR MINT; P10417; -.
DR STRING; 10090.ENSMUSP00000108371; -.
DR BindingDB; P10417; -.
DR ChEMBL; CHEMBL3309111; -.
DR iPTMnet; P10417; -.
DR PhosphoSitePlus; P10417; -.
DR EPD; P10417; -.
DR PaxDb; P10417; -.
DR PeptideAtlas; P10417; -.
DR PRIDE; P10417; -.
DR ProteomicsDB; 273655; -. [P10417-1]
DR ProteomicsDB; 273656; -. [P10417-2]
DR Antibodypedia; 3491; 3923 antibodies from 60 providers.
DR DNASU; 12043; -.
DR Ensembl; ENSMUST00000112751; ENSMUSP00000108371; ENSMUSG00000057329. [P10417-1]
DR Ensembl; ENSMUST00000189999; ENSMUSP00000139856; ENSMUSG00000057329. [P10417-2]
DR GeneID; 12043; -.
DR KEGG; mmu:12043; -.
DR UCSC; uc007cgw.2; mouse. [P10417-1]
DR CTD; 596; -.
DR MGI; MGI:88138; Bcl2.
DR VEuPathDB; HostDB:ENSMUSG00000057329; -.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244953; -.
DR HOGENOM; CLU_085401_0_0_1; -.
DR InParanoid; P10417; -.
DR OMA; QRGYDWA; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; P10417; -.
DR TreeFam; TF315834; -.
DR Reactome; R-MMU-111447; Activation of BAD and translocation to mitochondria.
DR Reactome; R-MMU-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
DR Reactome; R-MMU-844455; The NLRP1 inflammasome.
DR BioGRID-ORCS; 12043; 6 hits in 77 CRISPR screens.
DR ChiTaRS; Bcl2; mouse.
DR PRO; PR:P10417; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P10417; protein.
DR Bgee; ENSMUSG00000057329; Expressed in epithelium of cochlear duct and 230 other tissues.
DR ExpressionAtlas; P10417; baseline and differential.
DR Genevisible; P10417; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0030061; C:mitochondrial crista; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043209; C:myelin sheath; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0046930; C:pore complex; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0051400; F:BH domain binding; ISO:MGI.
DR GO; GO:0051434; F:BH3 domain binding; ISO:MGI.
DR GO; GO:0015267; F:channel activity; ISO:MGI.
DR GO; GO:0016248; F:channel inhibitor activity; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; IMP:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0031103; P:axon regeneration; IDA:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0001783; P:B cell apoptotic process; IDA:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0002326; P:B cell lineage commitment; IMP:MGI.
DR GO; GO:0042100; P:B cell proliferation; ISO:MGI.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IDA:MGI.
DR GO; GO:0060402; P:calcium ion transport into cytosol; IGI:MGI.
DR GO; GO:0043375; P:CD8-positive, alpha-beta T cell lineage commitment; IMP:MGI.
DR GO; GO:0016477; P:cell migration; IMP:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; IDA:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0021747; P:cochlear nucleus development; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; ISO:MGI.
DR GO; GO:0097048; P:dendritic cell apoptotic process; IDA:MGI.
DR GO; GO:0048589; P:developmental growth; IMP:MGI.
DR GO; GO:0048066; P:developmental pigmentation; IMP:MGI.
DR GO; GO:0048546; P:digestive tract morphogenesis; IMP:MGI.
DR GO; GO:0043583; P:ear development; IMP:MGI.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IGI:MGI.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IGI:MGI.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0022612; P:gland morphogenesis; IMP:MGI.
DR GO; GO:0032835; P:glomerulus development; IMP:MGI.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:UniProtKB.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IMP:MGI.
DR GO; GO:0002520; P:immune system development; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IGI:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:MGI.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0001776; P:leukocyte homeostasis; IMP:MGI.
DR GO; GO:0070227; P:lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:0002260; P:lymphocyte homeostasis; IMP:MGI.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IGI:MGI.
DR GO; GO:0006582; P:melanin metabolic process; IMP:MGI.
DR GO; GO:0030318; P:melanocyte differentiation; IMP:MGI.
DR GO; GO:0014031; P:mesenchymal cell development; IMP:MGI.
DR GO; GO:0001656; P:metanephros development; IMP:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IDA:MGI.
DR GO; GO:0097049; P:motor neuron apoptotic process; IDA:MGI.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IDA:MGI.
DR GO; GO:2000811; P:negative regulation of anoikis; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; IDA:MGI.
DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IGI:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0032848; P:negative regulation of cellular pH reduction; ISO:MGI.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:MGI.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:MGI.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0070229; P:negative regulation of lymphocyte apoptotic process; IMP:MGI.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:MGI.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IDA:MGI.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IDA:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:MGI.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IMP:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046671; P:negative regulation of retinal cell programmed cell death; IMP:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IDA:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IDA:MGI.
DR GO; GO:0070997; P:neuron death; IMP:MGI.
DR GO; GO:0042551; P:neuron maturation; IMP:MGI.
DR GO; GO:0048599; P:oocyte development; IMP:MGI.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0033687; P:osteoblast proliferation; IMP:MGI.
DR GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0048753; P:pigment granule organization; IMP:MGI.
DR GO; GO:0043473; P:pigmentation; IMP:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0048087; P:positive regulation of developmental pigmentation; IGI:MGI.
DR GO; GO:0045636; P:positive regulation of melanocyte differentiation; IMP:MGI.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0014042; P:positive regulation of neuron maturation; IMP:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:MGI.
DR GO; GO:0048743; P:positive regulation of skeletal muscle fiber development; IMP:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0006470; P:protein dephosphorylation; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IGI:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IMP:CACAO.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0050790; P:regulation of catalytic activity; IMP:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IMP:MGI.
DR GO; GO:0048070; P:regulation of developmental pigmentation; IGI:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0010559; P:regulation of glycoprotein biosynthetic process; IMP:MGI.
DR GO; GO:0040008; P:regulation of growth; IMP:MGI.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IDA:HGNC-UCL.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IDA:HGNC-UCL.
DR GO; GO:0006808; P:regulation of nitrogen utilization; IGI:MGI.
DR GO; GO:0043067; P:regulation of programmed cell death; IGI:MGI.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0031647; P:regulation of protein stability; IMP:MGI.
DR GO; GO:0022898; P:regulation of transmembrane transporter activity; ISO:MGI.
DR GO; GO:0045069; P:regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:HGNC-UCL.
DR GO; GO:0003014; P:renal system process; IMP:MGI.
DR GO; GO:0034097; P:response to cytokine; IMP:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:MGI.
DR GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; IMP:MGI.
DR GO; GO:1904373; P:response to kainic acid; IDA:MGI.
DR GO; GO:0035094; P:response to nicotine; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0048545; P:response to steroid hormone; IMP:MGI.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR GO; GO:0010224; P:response to UV-B; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0046666; P:retinal cell programmed cell death; IMP:MGI.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:MGI.
DR GO; GO:0014909; P:smooth muscle cell migration; IMP:MGI.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR GO; GO:0048864; P:stem cell development; IMP:MGI.
DR GO; GO:0070231; P:T cell apoptotic process; IDA:MGI.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI.
DR GO; GO:0043029; P:T cell homeostasis; IMP:MGI.
DR GO; GO:0002360; P:T cell lineage commitment; IMP:MGI.
DR GO; GO:0048538; P:thymus development; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013278; Apop_reg_Bcl2.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR004725; Bcl2/BclX.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR020728; Bcl2_BH3_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF11; PTHR11256:SF11; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01863; APOPREGBCL2.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SMART; SM00265; BH4; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR TIGRFAMs; TIGR00865; bcl-2; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01259; BH3; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cytoplasm; Endoplasmic reticulum;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..236
FT /note="Apoptosis regulator Bcl-2"
FT /id="PRO_0000143049"
FT TRANSMEM 209..230
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 10..30
FT /note="BH4"
FT MOTIF 90..104
FT /note="BH3"
FT MOTIF 133..152
FT /note="BH1"
FT MOTIF 184..199
FT /note="BH2"
FT SITE 34..35
FT /note="Cleavage; by caspases"
FT /evidence="ECO:0000250"
FT MOD_RES 69
FT /note="Phosphothreonine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT MOD_RES 70
FT /note="Phosphoserine; by MAPK8 and PKC"
FT /evidence="ECO:0000269|PubMed:9115213"
FT MOD_RES 84
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P10415"
FT VAR_SEQ 193..236
FT /note="DAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK -> VGAC
FT LVE (in isoform Beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_000513"
FT MUTAGEN 70
FT /note="S->A: Loss of phosphorylation. Unable to suppress
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:9115213"
FT CONFLICT 64
FT /note="D -> E (in Ref. 1; AAA37281/AAA37282)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="V -> C (in Ref. 1; AAA37281/AAA37282)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 236 AA; 26407 MW; 80FDCFE78C735092 CRC64;
MAQAGRTGYD NREIVMKYIH YKLSQRGYEW DAGDADAAPL GAAPTPGIFS FQPESNPMPA
VHRDMAARTS PLRPLVATAG PALSPVPPVV HLTLRRAGDD FSRRYRRDFA EMSSQLHLTP
FTARGRFATV VEELFRDGVN WGRIVAFFEF GGVMCVESVN REMSPLVDNI ALWMTEYLNR
HLHTWIQDNG GWDAFVELYG PSMRPLFDFS WLSLKTLLSL ALVGACITLG AYLGHK
