ID:BCL2_HUMAN DESCRIPTION: RecName: Full=Apoptosis regulator Bcl-2; FUNCTION: Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). SUBUNIT: Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). Interacts with EI24 (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser- 338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. INTERACTION: Self; NbExp=3; IntAct=EBI-77694, EBI-77694; Q92934:BAD; NbExp=5; IntAct=EBI-77694, EBI-700771; Q61337:Bad (xeno); NbExp=6; IntAct=EBI-77694, EBI-400328; Q07812:BAX; NbExp=8; IntAct=EBI-77694, EBI-516580; Q9BXH1:BBC3; NbExp=5; IntAct=EBI-77694, EBI-519884; P51572:BCAP31; NbExp=2; IntAct=EBI-77694, EBI-77683; O43521:BCL2L11; NbExp=4; IntAct=EBI-77694, EBI-526406; O43521-1:BCL2L11; NbExp=3; IntAct=EBI-77694, EBI-526416; O43521-2:BCL2L11; NbExp=4; IntAct=EBI-77694, EBI-526420; Q14457:BECN1; NbExp=3; IntAct=EBI-77694, EBI-949378; P55957:BID; NbExp=8; IntAct=EBI-77694, EBI-519672; Q13323:BIK; NbExp=3; IntAct=EBI-77694, EBI-700794; Q91ZE9:Bmf (xeno); NbExp=2; IntAct=EBI-77694, EBI-708032; O60238:BNIP3L; NbExp=2; IntAct=EBI-77694, EBI-849893; Q9C000:NLRP1; NbExp=12; IntAct=EBI-77694, EBI-1220518; P22736:NR4A1; NbExp=7; IntAct=EBI-77694, EBI-721550; Q13794:PMAIP1; NbExp=3; IntAct=EBI-77694, EBI-707392; O15304:SIVA1; NbExp=2; IntAct=EBI-77694, EBI-520756; P04637:TP53; NbExp=3; IntAct=EBI-77694, EBI-366083; SUBCELLULAR LOCATION: Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. TISSUE SPECIFICITY: Expressed in a variety of tissues. DOMAIN: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3. PTM: Phosphorylation/dephosphorylation on Ser-70 regulates anti- apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A (PP2A) (By similarity). PTM: Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity. PTM: Monoubiquitinated by PARK2, leading to increase its stability. DISEASE: Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. SIMILARITY: Belongs to the Bcl-2 family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BCL2ID49.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/bcl2/"; WEB RESOURCE: Name=Wikipedia; Note=Bcl-2 entry; URL="http://en.wikipedia.org/wiki/Bcl-2";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P10415
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000209 protein polyubiquitination GO:0000902 cell morphogenesis GO:0001503 ossification GO:0001541 ovarian follicle development GO:0001656 metanephros development GO:0001657 ureteric bud development GO:0001658 branching involved in ureteric bud morphogenesis GO:0001662 behavioral fear response GO:0001776 leukocyte homeostasis GO:0001782 B cell homeostasis GO:0001822 kidney development GO:0001836 release of cytochrome c from mitochondria GO:0001952 regulation of cell-matrix adhesion GO:0002260 lymphocyte homeostasis GO:0002320 lymphoid progenitor cell differentiation GO:0002326 B cell lineage commitment GO:0002360 T cell lineage commitment GO:0002520 immune system development GO:0002931 response to ischemia GO:0003014 renal system process GO:0006470 protein dephosphorylation GO:0006582 melanin metabolic process GO:0006808 regulation of nitrogen utilization GO:0006874 cellular calcium ion homeostasis GO:0006915 apoptotic process GO:0006959 humoral immune response GO:0006974 cellular response to DNA damage stimulus GO:0006979 response to oxidative stress GO:0007015 actin filament organization GO:0007409 axonogenesis GO:0007565 female pregnancy GO:0007569 cell aging GO:0008283 cell proliferation GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0008584 male gonad development GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress GO:0008637 apoptotic mitochondrial changes GO:0009314 response to radiation GO:0009636 response to toxic substance GO:0009791 post-embryonic development GO:0009887 animal organ morphogenesis GO:0010039 response to iron ion GO:0010224 response to UV-B GO:0010332 response to gamma radiation GO:0010468 regulation of gene expression GO:0010506 regulation of autophagy GO:0010507 negative regulation of autophagy GO:0010523 negative regulation of calcium ion transport into cytosol GO:0010559 regulation of glycoprotein biosynthetic process GO:0014031 mesenchymal cell development GO:0014042 positive regulation of neuron maturation GO:0014911 positive regulation of smooth muscle cell migration GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0019221 cytokine-mediated signaling pathway GO:0021747 cochlear nucleus development GO:0022612 gland morphogenesis GO:0022898 regulation of transmembrane transporter activity GO:0030097 hemopoiesis GO:0030183 B cell differentiation GO:0030217 T cell differentiation GO:0030279 negative regulation of ossification GO:0030307 positive regulation of cell growth GO:0030308 negative regulation of cell growth GO:0030318 melanocyte differentiation GO:0030336 negative regulation of cell migration GO:0030890 positive regulation of B cell proliferation GO:0031069 hair follicle morphogenesis GO:0031103 axon regeneration GO:0031647 regulation of protein stability GO:0032469 endoplasmic reticulum calcium ion homeostasis GO:0032835 glomerulus development GO:0032848 negative regulation of cellular pH reduction GO:0032880 regulation of protein localization GO:0033033 negative regulation of myeloid cell apoptotic process GO:0033077 T cell differentiation in thymus GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033689 negative regulation of osteoblast proliferation GO:0034097 response to cytokine GO:0035094 response to nicotine GO:0035265 organ growth GO:0040007 growth GO:0040018 positive regulation of multicellular organism growth GO:0042100 B cell proliferation GO:0042149 cellular response to glucose starvation GO:0042493 response to drug GO:0042542 response to hydrogen peroxide GO:0042981 regulation of apoptotic process GO:0043029 T cell homeostasis GO:0043066 negative regulation of apoptotic process GO:0043067 regulation of programmed cell death GO:0043085 positive regulation of catalytic activity GO:0043375 CD8-positive, alpha-beta T cell lineage commitment GO:0043473 pigmentation GO:0043496 regulation of protein homodimerization activity GO:0043497 regulation of protein heterodimerization activity GO:0043524 negative regulation of neuron apoptotic process GO:0043583 ear development GO:0045069 regulation of viral genome replication GO:0045636 positive regulation of melanocyte differentiation GO:0045930 negative regulation of mitotic cell cycle GO:0046671 negative regulation of retinal cell programmed cell death GO:0046902 regulation of mitochondrial membrane permeability GO:0048041 focal adhesion assembly GO:0048066 developmental pigmentation GO:0048070 regulation of developmental pigmentation GO:0048087 positive regulation of developmental pigmentation GO:0048536 spleen development GO:0048538 thymus development GO:0048545 response to steroid hormone GO:0048546 digestive tract morphogenesis GO:0048589 developmental growth GO:0048599 oocyte development GO:0048743 positive regulation of skeletal muscle fiber development GO:0048753 pigment granule organization GO:0048873 homeostasis of number of cells within a tissue GO:0050790 regulation of catalytic activity GO:0050853 B cell receptor signaling pathway GO:0051384 response to glucocorticoid GO:0051402 neuron apoptotic process GO:0051607 defense response to virus GO:0051726 regulation of cell cycle GO:0051881 regulation of mitochondrial membrane potential GO:0051902 negative regulation of mitochondrial depolarization GO:0051924 regulation of calcium ion transport GO:0055085 transmembrane transport GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0071310 cellular response to organic substance GO:0071456 cellular response to hypoxia GO:0072593 reactive oxygen species metabolic process GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0098609 cell-cell adhesion GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:2000134 negative regulation of G1/S transition of mitotic cell cycle GO:2000378 negative regulation of reactive oxygen species metabolic process GO:2000811 negative regulation of anoikis GO:2001234 negative regulation of apoptotic signaling pathway GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand GO:2001243 negative regulation of intrinsic apoptotic signaling pathway GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
