ID:BAD_HUMAN DESCRIPTION: RecName: Full=Bcl2 antagonist of cell death; Short=BAD; AltName: Full=Bcl-2-binding component 6; AltName: Full=Bcl-2-like protein 8; Short=Bcl2-L-8; AltName: Full=Bcl-XL/Bcl-2-associated death promoter; FUNCTION: Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways. SUBUNIT: Forms heterodimers with the anti-apoptotic proteins, Bcl- X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity). The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins (By similarity). Interacts with AKT1 and PIM3. INTERACTION: P10415:BCL2; NbExp=5; IntAct=EBI-700771, EBI-77694; Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-700771, EBI-287195; O60238:BNIP3L; NbExp=2; IntAct=EBI-700771, EBI-849893; SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cytoplasm. Note=Upon phosphorylation, locates to the cytoplasm. TISSUE SPECIFICITY: Expressed in a wide variety of tissues. DOMAIN: Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. PTM: Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 and Ser-134 in response to survival stimuli, which blocks its pro- apoptotic activity. Phosphorylation on Ser-99 or Ser-75 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-118, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-99 is the major site of AKT/PKB phosphorylation, Ser-118 the major site of protein kinase A (CAPK) phosphorylation. Phosphorylation at Ser-99 by PKB/AKT1 is almost completely blocked by the apoptotic C-terminus cleavage product of PKN2 generated by caspases-3 activity during apoptosis. PTM: Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt- mediated phosphorylation at Ser-99. SIMILARITY: Belongs to the Bcl-2 family. SEQUENCE CAUTION: Sequence=AAB36516.1; Type=Frameshift; Positions=64, 91; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BADID130ch11q13.html"; WEB RESOURCE: Name=Wikipedia; Note=Bcl 2-associated death promoter entry; URL="http://en.wikipedia.org/wiki/Bcl-2-associated_death_promoter";
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 Q92934
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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.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0005543 phospholipid binding GO:0008289 lipid binding GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0019901 protein kinase binding GO:0019903 protein phosphatase binding GO:0030346 protein phosphatase 2B binding GO:0043422 protein kinase B binding GO:0046982 protein heterodimerization activity GO:0071889 14-3-3 protein binding
Biological Process: GO:0001666 response to hypoxia GO:0001836 release of cytochrome c from mitochondria GO:0001844 protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:0006007 glucose catabolic process GO:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007283 spermatogenesis GO:0008283 cell proliferation GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0009725 response to hormone GO:0009749 response to glucose GO:0010033 response to organic substance GO:0010508 positive regulation of autophagy GO:0010918 positive regulation of mitochondrial membrane potential GO:0014070 response to organic cyclic compound GO:0019050 suppression by virus of host apoptotic process GO:0019221 cytokine-mediated signaling pathway GO:0021987 cerebral cortex development GO:0032024 positive regulation of insulin secretion GO:0032355 response to estradiol GO:0032570 response to progesterone GO:0033133 positive regulation of glucokinase activity GO:0033574 response to testosterone GO:0034201 response to oleic acid GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus GO:0042493 response to drug GO:0042542 response to hydrogen peroxide GO:0042593 glucose homeostasis GO:0042981 regulation of apoptotic process GO:0043065 positive regulation of apoptotic process GO:0043200 response to amino acid GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0044342 type B pancreatic cell proliferation GO:0045471 response to ethanol GO:0045579 positive regulation of B cell differentiation GO:0045582 positive regulation of T cell differentiation GO:0045862 positive regulation of proteolysis GO:0046031 ADP metabolic process GO:0046034 ATP metabolic process GO:0046902 regulation of mitochondrial membrane permeability GO:0046931 pore complex assembly GO:0050679 positive regulation of epithelial cell proliferation GO:0051384 response to glucocorticoid GO:0051592 response to calcium ion GO:0060139 positive regulation of apoptotic process by virus GO:0060154 cellular process regulating host cell cycle in response to virus GO:0071247 cellular response to chromate GO:0071260 cellular response to mechanical stimulus GO:0071316 cellular response to nicotine GO:0071396 cellular response to lipid GO:0071456 cellular response to hypoxia GO:0090200 positive regulation of release of cytochrome c from mitochondria GO:0097190 apoptotic signaling pathway GO:0097191 extrinsic apoptotic signaling pathway GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:0097193 intrinsic apoptotic signaling pathway GO:0097202 activation of cysteine-type endopeptidase activity GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1901216 positive regulation of neuron death GO:1902220 positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress GO:2000078 positive regulation of type B pancreatic cell development GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
LF211208 - JP 2014500723-A/18711: Polycomb-Associated Non-Coding RNAs. LF385501 - JP 2014500723-A/193004: Polycomb-Associated Non-Coding RNAs. U66879 - Homo sapiens Bcl-2 binding component 6 (bbc6) mRNA, complete cds. AF021792 - Homo sapiens Bcl-X/Bcl-2 binding protein (BAD) mRNA, partial cds. BC001901 - Homo sapiens BCL2-associated agonist of cell death, mRNA (cDNA clone MGC:2100 IMAGE:3537914), complete cds. AK303051 - Homo sapiens cDNA FLJ61193 complete cds, highly similar to Bcl2 antagonist of cell death. BC095431 - Homo sapiens BCL2-associated agonist of cell death, mRNA (cDNA clone MGC:111080 IMAGE:30377088), complete cds. AK291863 - Homo sapiens cDNA FLJ75743 complete cds, highly similar to Homo sapiens BCL2-antagonist of cell death (BAD), transcript variant 1, mRNA. JD191060 - Sequence 172084 from Patent EP1572962. JD128860 - Sequence 109884 from Patent EP1572962. JD230954 - Sequence 211978 from Patent EP1572962. JD516400 - Sequence 497424 from Patent EP1572962. JD127429 - Sequence 108453 from Patent EP1572962. AF031523 - Homo sapiens bcl-xL/bcl-2 associated death promoter (BAD) mRNA, complete cds. CR541935 - Homo sapiens full open reading frame cDNA clone RZPDo834A0634D for gene BAD, BCL2-antagonist of cell death; complete cds, incl. stopcodon. KJ890752 - Synthetic construct Homo sapiens clone ccsbBroadEn_00146 BAD gene, encodes complete protein. AB451254 - Homo sapiens BAD mRNA for BCL2-antagonist of cell death protein, complete cds, clone: FLJ08066AAAN. BT006678 - Homo sapiens BCL2-antagonist of cell death mRNA, complete cds. DQ895784 - Synthetic construct Homo sapiens clone IMAGE:100010244; FLH187627.01L; RZPDo839B06149D BCL2-antagonist of cell death (BAD) gene, encodes complete protein. AB451378 - Homo sapiens BAD mRNA for BCL2-antagonist of cell death protein, partial cds, clone: FLJ08066AAAF. CR541959 - Homo sapiens full open reading frame cDNA clone RZPDo834G0534D for gene BAD, BCL2-antagonist of cell death; complete cds, without stopcodon. AB463436 - Synthetic construct DNA, clone: pF1KB8229, Homo sapiens BAD gene for BCL2-antagonist of cell death, without stop codon, in Flexi system. EU176363 - Synthetic construct Homo sapiens clone IMAGE:100006468; FLH187634.01X; RZPDo839C11251D BCL2-antagonist of cell death (BAD) gene, encodes complete protein. CU674924 - Synthetic construct Homo sapiens gateway clone IMAGE:100017955 5' read BAD mRNA. AK309150 - Homo sapiens cDNA, FLJ99191. JD513001 - Sequence 494025 from Patent EP1572962. JD211177 - Sequence 192201 from Patent EP1572962. MA621078 - JP 2018138019-A/193004: Polycomb-Associated Non-Coding RNAs. MA446785 - JP 2018138019-A/18711: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_achPathway - Role of nicotinic acetylcholine receptors in the regulation of apoptosis h_aktPathway - AKT Signaling Pathway h_gleevecpathway - Inhibition of Cellular Proliferation by Gleevec h_igf1rPathway - Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation h_ptdinsPathway - Phosphoinositides and their downstream targets. h_rasPathway - Ras Signaling Pathway h_ceramidePathway - Ceramide Signaling Pathway h_chemicalPathway - Apoptotic Signaling in Response to DNA Damage h_tffPathway - Trefoil Factors Initiate Mucosal Healing h_il2rbPathway - IL-2 Receptor Beta Chain in T cell Activation h_badPathway - Regulation of BAD phosphorylation
Reactome (by CSHL, EBI, and GO)
Protein Q92934 (Reactome details) participates in the following event(s):
R-HSA-139905 Translocation of activated BAD protein to mitochondria R-HSA-198347 AKT phosphorylates BAD R-HSA-205075 JNK phosphorylates BIM, BAD and other targets R-HSA-2399941 AKT1 E17K mutant phosphorylates BAD R-HSA-139906 Activation of BAD by calcineurin R-HSA-139897 BAD displaces tBID from BCL-2 sequestration R-HSA-139899 Sequestration of BAD protein by 14-3-3 R-HSA-508162 BH3 only proteins associate with and inactivate anti-apoptotic BCL-XL R-HSA-508163 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 R-HSA-111447 Activation of BAD and translocation to mitochondria R-HSA-198323 AKT phosphorylates targets in the cytosol R-HSA-193648 NRAGE signals death through JNK R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer R-HSA-114452 Activation of BH3-only proteins R-HSA-1257604 PIP3 activates AKT signaling R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members R-HSA-109606 Intrinsic Pathway for Apoptosis R-HSA-9006925 Intracellular signaling by second messengers R-HSA-193704 p75 NTR receptor-mediated signalling R-HSA-5663202 Diseases of signal transduction R-HSA-109581 Apoptosis R-HSA-162582 Signal Transduction R-HSA-73887 Death Receptor Signalling R-HSA-1643685 Disease R-HSA-5357801 Programmed Cell Death