Full text data of BAD
BAD
(BBC6, BCL2L8)
[Confidence: low (only semi-automatic identification from reviews)]
Bcl2 antagonist of cell death; BAD (Bcl-2-binding component 6; Bcl-2-like protein 8; Bcl2-L-8; Bcl-XL/Bcl-2-associated death promoter)
Bcl2 antagonist of cell death; BAD (Bcl-2-binding component 6; Bcl-2-like protein 8; Bcl2-L-8; Bcl-XL/Bcl-2-associated death promoter)
UniProt
Q92934
ID BAD_HUMAN Reviewed; 168 AA.
AC Q92934; O14803; Q6FH21;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 3.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Bcl2 antagonist of cell death;
DE Short=BAD;
DE AltName: Full=Bcl-2-binding component 6;
DE AltName: Full=Bcl-2-like protein 8;
DE Short=Bcl2-L-8;
DE AltName: Full=Bcl-XL/Bcl-2-associated death promoter;
GN Name=BAD; Synonyms=BBC6, BCL2L8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yin D.X., Li Z., Huang B., Chen S., Zhou H.;
RT "A human protein that interacts with Bcl-2 and have homology to mouse
RT BAD.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION BY RAF-1.
RX PubMed=8929532; DOI=10.1016/S0092-8674(00)81383-5;
RA Wang H.-G., Rapp U.R., Reed J.C.;
RT "Bcl-2 targets the protein kinase Raf-1 to mitochondria.";
RL Cell 87:629-638(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Takayama S., Reed J.C.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DIMERIZATION.
RC TISSUE=Bone marrow;
RX PubMed=9388232; DOI=10.1074/jbc.272.49.30866;
RA Ottilie S., Diaz J.-L., Horne W., Chang J., Wang Y., Wilson G.,
RA Chang S., Weeks S., Fritz L.C., Oltersdorf T.;
RT "Dimerization properties of human BAD. Identification of a BH-3 domain
RT and analysis of its binding to mutant BCL-2 and BCL-XL proteins.";
RL J. Biol. Chem. 272:30866-30872(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP INTERACTION WITH AKT1, AND PHOSPHORYLATION AT SER-99.
RX PubMed=10926925; DOI=10.1074/jbc.M001753200;
RA Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.;
RT "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis
RT factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.";
RL J. Biol. Chem. 275:34451-34458(2000).
RN [12]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=11278822; DOI=10.1074/jbc.M011046200;
RA Gnesutta N., Qu J., Minden A.;
RT "The serine/threonine kinase PAK4 prevents caspase activation and
RT protects cells from apoptosis.";
RL J. Biol. Chem. 276:14414-14419(2001).
RN [13]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=12897128; DOI=10.1128/MCB.23.16.5526-5539.2003;
RA Cotteret S., Jaffer Z.M., Beeser A., Chernoff J.;
RT "p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits
RT apoptosis by phosphorylating BAD.";
RL Mol. Cell. Biol. 23:5526-5539(2003).
RN [14]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=16818649; DOI=10.1158/0008-5472.CAN-05-4272;
RA Li Y.Y., Popivanova B.K., Nagai Y., Ishikura H., Fujii C., Mukaida N.;
RT "Pim-3, a proto-oncogene with serine/threonine kinase activity, is
RT aberrantly expressed in human pancreatic cancer and phosphorylates bad
RT to block bad-mediated apoptosis in human pancreatic cancer cell
RT lines.";
RL Cancer Res. 66:6741-6747(2006).
RN [15]
RP INTERACTION WITH PIM3.
RX PubMed=17270021; DOI=10.1111/j.1349-7006.2007.00390.x;
RA Popivanova B.K., Li Y.Y., Zheng H., Omura K., Fujii C., Tsuneyama K.,
RA Mukaida N.;
RT "Proto-oncogene, Pim-3 with serine/threonine kinase activity, is
RT aberrantly expressed in human colon cancer cells and can prevent Bad-
RT mediated apoptosis.";
RL Cancer Sci. 98:321-328(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91 AND SER-118, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP METHYLATION AT ARG-94 AND ARG-96 BY PRMT1, AND MUTAGENESIS OF ARG-94
RP AND ARG-96.
RX PubMed=21444773; DOI=10.1073/pnas.1015328108;
RA Sakamaki J., Daitoku H., Ueno K., Hagiwara A., Yamagata K.,
RA Fukamizu A.;
RT "Arginine methylation of BCL-2 antagonist of cell death (BAD)
RT counteracts its phosphorylation and inactivation by Akt.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:6085-6090(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP STRUCTURE BY NMR OF 103-127.
RX PubMed=11206074; DOI=10.1017/S096183680000331X;
RA Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P.,
RA Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B.,
RA Fesik S.W.;
RT "Rationale for Bcl-xL/Bad peptide complex formation from structure,
RT mutagenesis, and biophysical studies.";
RL Protein Sci. 9:2528-2534(2000).
CC -!- FUNCTION: Promotes cell death. Successfully competes for the
CC binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level
CC of heterodimerization of these proteins with BAX. Can reverse the
CC death repressor activity of Bcl-X(L), but not that of Bcl-2 (By
CC similarity). Appears to act as a link between growth factor
CC receptor signaling and the apoptotic pathways.
CC -!- SUBUNIT: Forms heterodimers with the anti-apoptotic proteins, Bcl-
CC X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity).
CC The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins (By
CC similarity). Interacts with AKT1 and PIM3.
CC -!- INTERACTION:
CC P10415:BCL2; NbExp=5; IntAct=EBI-700771, EBI-77694;
CC Q07817:BCL2L1; NbExp=2; IntAct=EBI-700771, EBI-78035;
CC Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-700771, EBI-287195;
CC O43521:BCL2L11; NbExp=2; IntAct=EBI-700771, EBI-526406;
CC O60238:BNIP3L; NbExp=2; IntAct=EBI-700771, EBI-849893;
CC P45983:MAPK8; NbExp=2; IntAct=EBI-700771, EBI-286483;
CC P31947:SFN; NbExp=4; IntAct=EBI-700771, EBI-476295;
CC P17361:VACWR028 (xeno); NbExp=2; IntAct=EBI-700771, EBI-7115640;
CC P63104:YWHAZ; NbExp=5; IntAct=EBI-700771, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cytoplasm.
CC Note=Upon phosphorylation, locates to the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of tissues.
CC -!- DOMAIN: Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX
CC for their pro-apoptotic activity and for their interaction with
CC anti-apoptotic members of the Bcl-2 family.
CC -!- PTM: Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 and
CC Ser-134 in response to survival stimuli, which blocks its pro-
CC apoptotic activity. Phosphorylation on Ser-99 or Ser-75 promotes
CC heterodimerization with 14-3-3 proteins. This interaction then
CC facilitates the phosphorylation at Ser-118, a site within the BH3
CC motif, leading to the release of Bcl-X(L) and the promotion of
CC cell survival. Ser-99 is the major site of AKT/PKB
CC phosphorylation, Ser-118 the major site of protein kinase A (CAPK)
CC phosphorylation. Phosphorylation at Ser-99 by PKB/AKT1 is almost
CC completely blocked by the apoptotic C-terminus cleavage product of
CC PKN2 generated by caspases-3 activity during apoptosis.
CC -!- PTM: Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt-
CC mediated phosphorylation at Ser-99.
CC -!- SIMILARITY: Belongs to the Bcl-2 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB36516.1; Type=Frameshift; Positions=64, 91;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BADID130ch11q13.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bcl 2-associated death promoter
CC entry;
CC URL="http://en.wikipedia.org/wiki/Bcl-2-associated_death_promoter";
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DR EMBL; U66879; AAB36516.1; ALT_FRAME; mRNA.
DR EMBL; AF021792; AAB72092.1; -; mRNA.
DR EMBL; AF031523; AAB88124.1; -; mRNA.
DR EMBL; AK291863; BAF84552.1; -; mRNA.
DR EMBL; BT006678; AAP35324.1; -; mRNA.
DR EMBL; CR541935; CAG46733.1; -; mRNA.
DR EMBL; CR541959; CAG46757.1; -; mRNA.
DR EMBL; AB451254; BAG70068.1; -; mRNA.
DR EMBL; AB451378; BAG70192.1; -; mRNA.
DR EMBL; CH471076; EAW74235.1; -; Genomic_DNA.
DR EMBL; BC001901; AAH01901.1; -; mRNA.
DR EMBL; BC095431; AAH95431.1; -; mRNA.
DR RefSeq; NP_004313.1; NM_004322.3.
DR RefSeq; NP_116784.1; NM_032989.2.
DR UniGene; Hs.370254; -.
DR PDB; 1G5J; NMR; -; B=103-127.
DR PDBsum; 1G5J; -.
DR ProteinModelPortal; Q92934; -.
DR SMR; Q92934; 100-126.
DR DIP; DIP-29184N; -.
DR IntAct; Q92934; 28.
DR MINT; MINT-216253; -.
DR STRING; 9606.ENSP00000309103; -.
DR BindingDB; Q92934; -.
DR ChEMBL; CHEMBL3817; -.
DR PhosphoSite; Q92934; -.
DR DMDM; 17371773; -.
DR PaxDb; Q92934; -.
DR PeptideAtlas; Q92934; -.
DR PRIDE; Q92934; -.
DR DNASU; 572; -.
DR Ensembl; ENST00000309032; ENSP00000309103; ENSG00000002330.
DR Ensembl; ENST00000394532; ENSP00000378040; ENSG00000002330.
DR GeneID; 572; -.
DR KEGG; hsa:572; -.
DR UCSC; uc001nzc.3; human.
DR CTD; 572; -.
DR GeneCards; GC11M064037; -.
DR HGNC; HGNC:936; BAD.
DR HPA; CAB004205; -.
DR HPA; HPA028185; -.
DR MIM; 603167; gene.
DR neXtProt; NX_Q92934; -.
DR PharmGKB; PA25236; -.
DR eggNOG; NOG43412; -.
DR HOGENOM; HOG000095169; -.
DR HOVERGEN; HBG001653; -.
DR InParanoid; Q92934; -.
DR KO; K02158; -.
DR OMA; GEAGHQQ; -.
DR OrthoDB; EOG7MD4RF; -.
DR PhylomeDB; Q92934; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; BAD; human.
DR EvolutionaryTrace; Q92934; -.
DR GeneWiki; Bcl-2-associated_death_promoter; -.
DR GenomeRNAi; 572; -.
DR NextBio; 2331; -.
DR PMAP-CutDB; Q92934; -.
DR PRO; PR:Q92934; -.
DR ArrayExpress; Q92934; -.
DR Bgee; Q92934; -.
DR CleanEx; HS_BAD; -.
DR Genevestigator; Q92934; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IMP:UniProtKB.
DR GO; GO:0046031; P:ADP metabolic process; ISS:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB.
DR GO; GO:0060154; P:cellular process regulating host cell cycle in response to virus; IEA:Ensembl.
DR GO; GO:0071247; P:cellular response to chromate; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0071396; P:cellular response to lipid; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0071316; P:cellular response to nicotine; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006007; P:glucose catabolic process; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0046931; P:pore complex assembly; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; TAS:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISS:UniProtKB.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IEA:Ensembl.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:UniProtKB.
DR GO; GO:0043200; P:response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0034201; P:response to oleic acid; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone stimulus; IEA:Ensembl.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
DR InterPro; IPR018868; Bcl-2_BAD.
DR Pfam; PF10514; Bcl-2_BAD; 1.
DR PROSITE; PS01259; BH3; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Complete proteome; Cytoplasm;
KW Membrane; Methylation; Mitochondrion; Mitochondrion outer membrane;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 168 Bcl2 antagonist of cell death.
FT /FTId=PRO_0000143103.
FT MOTIF 110 124 BH3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 75 75 Phosphoserine; by PKA, PKB, PIM2, PIM3,
FT PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and
FT RAF1 (By similarity).
FT MOD_RES 91 91 Phosphoserine.
FT MOD_RES 94 94 Asymmetric dimethylarginine; by PRMT1.
FT MOD_RES 96 96 Asymmetric dimethylarginine; by PRMT1.
FT MOD_RES 99 99 Phosphoserine; by PKA, PKB, PAK1,
FT RPS6KA1, RPS6KB1 and PKC/PRKCQ; alternate
FT (By similarity).
FT MOD_RES 99 99 Phosphoserine; by PKB/AKT1; alternate.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 134 134 Phosphoserine (By similarity).
FT VARIANT 107 107 A -> S (in dbSNP:rs3729933).
FT /FTId=VAR_015380.
FT MUTAGEN 94 94 R->K: Decreased methylation; when
FT associated with K-96.
FT MUTAGEN 96 96 R->K: Decreased methylation; when
FT associated with K-94.
FT HELIX 106 121
SQ SEQUENCE 168 AA; 18392 MW; 69FD8D27DDEE3241 CRC64;
MFQIPEFEPS EQEDSSSAER GLGPSPAGDG PSGSGKHHRQ APGLLWDASH QQEQPTSSSH
HGGAGAVEIR SRHSSYPAGT EDDEGMGEEP SPFRGRSRSA PPNLWAAQRY GRELRRMSDE
FVDSFKKGLP RPKSAGTATQ MRQSSSWTRV FQSWWDRNLG RGSSAPSQ
//
ID BAD_HUMAN Reviewed; 168 AA.
AC Q92934; O14803; Q6FH21;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 26-SEP-2001, sequence version 3.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Bcl2 antagonist of cell death;
DE Short=BAD;
DE AltName: Full=Bcl-2-binding component 6;
DE AltName: Full=Bcl-2-like protein 8;
DE Short=Bcl2-L-8;
DE AltName: Full=Bcl-XL/Bcl-2-associated death promoter;
GN Name=BAD; Synonyms=BBC6, BCL2L8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yin D.X., Li Z., Huang B., Chen S., Zhou H.;
RT "A human protein that interacts with Bcl-2 and have homology to mouse
RT BAD.";
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION BY RAF-1.
RX PubMed=8929532; DOI=10.1016/S0092-8674(00)81383-5;
RA Wang H.-G., Rapp U.R., Reed J.C.;
RT "Bcl-2 targets the protein kinase Raf-1 to mitochondria.";
RL Cell 87:629-638(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Takayama S., Reed J.C.;
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DIMERIZATION.
RC TISSUE=Bone marrow;
RX PubMed=9388232; DOI=10.1074/jbc.272.49.30866;
RA Ottilie S., Diaz J.-L., Horne W., Chang J., Wang Y., Wilson G.,
RA Chang S., Weeks S., Fritz L.C., Oltersdorf T.;
RT "Dimerization properties of human BAD. Identification of a BH-3 domain
RT and analysis of its binding to mutant BCL-2 and BCL-XL proteins.";
RL J. Biol. Chem. 272:30866-30872(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP INTERACTION WITH AKT1, AND PHOSPHORYLATION AT SER-99.
RX PubMed=10926925; DOI=10.1074/jbc.M001753200;
RA Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.;
RT "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis
RT factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.";
RL J. Biol. Chem. 275:34451-34458(2000).
RN [12]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=11278822; DOI=10.1074/jbc.M011046200;
RA Gnesutta N., Qu J., Minden A.;
RT "The serine/threonine kinase PAK4 prevents caspase activation and
RT protects cells from apoptosis.";
RL J. Biol. Chem. 276:14414-14419(2001).
RN [13]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=12897128; DOI=10.1128/MCB.23.16.5526-5539.2003;
RA Cotteret S., Jaffer Z.M., Beeser A., Chernoff J.;
RT "p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits
RT apoptosis by phosphorylating BAD.";
RL Mol. Cell. Biol. 23:5526-5539(2003).
RN [14]
RP PHOSPHORYLATION AT SER-75.
RX PubMed=16818649; DOI=10.1158/0008-5472.CAN-05-4272;
RA Li Y.Y., Popivanova B.K., Nagai Y., Ishikura H., Fujii C., Mukaida N.;
RT "Pim-3, a proto-oncogene with serine/threonine kinase activity, is
RT aberrantly expressed in human pancreatic cancer and phosphorylates bad
RT to block bad-mediated apoptosis in human pancreatic cancer cell
RT lines.";
RL Cancer Res. 66:6741-6747(2006).
RN [15]
RP INTERACTION WITH PIM3.
RX PubMed=17270021; DOI=10.1111/j.1349-7006.2007.00390.x;
RA Popivanova B.K., Li Y.Y., Zheng H., Omura K., Fujii C., Tsuneyama K.,
RA Mukaida N.;
RT "Proto-oncogene, Pim-3 with serine/threonine kinase activity, is
RT aberrantly expressed in human colon cancer cells and can prevent Bad-
RT mediated apoptosis.";
RL Cancer Sci. 98:321-328(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91 AND SER-118, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP METHYLATION AT ARG-94 AND ARG-96 BY PRMT1, AND MUTAGENESIS OF ARG-94
RP AND ARG-96.
RX PubMed=21444773; DOI=10.1073/pnas.1015328108;
RA Sakamaki J., Daitoku H., Ueno K., Hagiwara A., Yamagata K.,
RA Fukamizu A.;
RT "Arginine methylation of BCL-2 antagonist of cell death (BAD)
RT counteracts its phosphorylation and inactivation by Akt.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:6085-6090(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP STRUCTURE BY NMR OF 103-127.
RX PubMed=11206074; DOI=10.1017/S096183680000331X;
RA Petros A.M., Nettesheim D.G., Wang Y., Olejniczak E.T., Meadows R.P.,
RA Mack J., Swift K., Matayoshi E.D., Zhang H., Thompson C.B.,
RA Fesik S.W.;
RT "Rationale for Bcl-xL/Bad peptide complex formation from structure,
RT mutagenesis, and biophysical studies.";
RL Protein Sci. 9:2528-2534(2000).
CC -!- FUNCTION: Promotes cell death. Successfully competes for the
CC binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level
CC of heterodimerization of these proteins with BAX. Can reverse the
CC death repressor activity of Bcl-X(L), but not that of Bcl-2 (By
CC similarity). Appears to act as a link between growth factor
CC receptor signaling and the apoptotic pathways.
CC -!- SUBUNIT: Forms heterodimers with the anti-apoptotic proteins, Bcl-
CC X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity).
CC The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins (By
CC similarity). Interacts with AKT1 and PIM3.
CC -!- INTERACTION:
CC P10415:BCL2; NbExp=5; IntAct=EBI-700771, EBI-77694;
CC Q07817:BCL2L1; NbExp=2; IntAct=EBI-700771, EBI-78035;
CC Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-700771, EBI-287195;
CC O43521:BCL2L11; NbExp=2; IntAct=EBI-700771, EBI-526406;
CC O60238:BNIP3L; NbExp=2; IntAct=EBI-700771, EBI-849893;
CC P45983:MAPK8; NbExp=2; IntAct=EBI-700771, EBI-286483;
CC P31947:SFN; NbExp=4; IntAct=EBI-700771, EBI-476295;
CC P17361:VACWR028 (xeno); NbExp=2; IntAct=EBI-700771, EBI-7115640;
CC P63104:YWHAZ; NbExp=5; IntAct=EBI-700771, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Cytoplasm.
CC Note=Upon phosphorylation, locates to the cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in a wide variety of tissues.
CC -!- DOMAIN: Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX
CC for their pro-apoptotic activity and for their interaction with
CC anti-apoptotic members of the Bcl-2 family.
CC -!- PTM: Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 and
CC Ser-134 in response to survival stimuli, which blocks its pro-
CC apoptotic activity. Phosphorylation on Ser-99 or Ser-75 promotes
CC heterodimerization with 14-3-3 proteins. This interaction then
CC facilitates the phosphorylation at Ser-118, a site within the BH3
CC motif, leading to the release of Bcl-X(L) and the promotion of
CC cell survival. Ser-99 is the major site of AKT/PKB
CC phosphorylation, Ser-118 the major site of protein kinase A (CAPK)
CC phosphorylation. Phosphorylation at Ser-99 by PKB/AKT1 is almost
CC completely blocked by the apoptotic C-terminus cleavage product of
CC PKN2 generated by caspases-3 activity during apoptosis.
CC -!- PTM: Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt-
CC mediated phosphorylation at Ser-99.
CC -!- SIMILARITY: Belongs to the Bcl-2 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB36516.1; Type=Frameshift; Positions=64, 91;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BADID130ch11q13.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bcl 2-associated death promoter
CC entry;
CC URL="http://en.wikipedia.org/wiki/Bcl-2-associated_death_promoter";
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DR EMBL; U66879; AAB36516.1; ALT_FRAME; mRNA.
DR EMBL; AF021792; AAB72092.1; -; mRNA.
DR EMBL; AF031523; AAB88124.1; -; mRNA.
DR EMBL; AK291863; BAF84552.1; -; mRNA.
DR EMBL; BT006678; AAP35324.1; -; mRNA.
DR EMBL; CR541935; CAG46733.1; -; mRNA.
DR EMBL; CR541959; CAG46757.1; -; mRNA.
DR EMBL; AB451254; BAG70068.1; -; mRNA.
DR EMBL; AB451378; BAG70192.1; -; mRNA.
DR EMBL; CH471076; EAW74235.1; -; Genomic_DNA.
DR EMBL; BC001901; AAH01901.1; -; mRNA.
DR EMBL; BC095431; AAH95431.1; -; mRNA.
DR RefSeq; NP_004313.1; NM_004322.3.
DR RefSeq; NP_116784.1; NM_032989.2.
DR UniGene; Hs.370254; -.
DR PDB; 1G5J; NMR; -; B=103-127.
DR PDBsum; 1G5J; -.
DR ProteinModelPortal; Q92934; -.
DR SMR; Q92934; 100-126.
DR DIP; DIP-29184N; -.
DR IntAct; Q92934; 28.
DR MINT; MINT-216253; -.
DR STRING; 9606.ENSP00000309103; -.
DR BindingDB; Q92934; -.
DR ChEMBL; CHEMBL3817; -.
DR PhosphoSite; Q92934; -.
DR DMDM; 17371773; -.
DR PaxDb; Q92934; -.
DR PeptideAtlas; Q92934; -.
DR PRIDE; Q92934; -.
DR DNASU; 572; -.
DR Ensembl; ENST00000309032; ENSP00000309103; ENSG00000002330.
DR Ensembl; ENST00000394532; ENSP00000378040; ENSG00000002330.
DR GeneID; 572; -.
DR KEGG; hsa:572; -.
DR UCSC; uc001nzc.3; human.
DR CTD; 572; -.
DR GeneCards; GC11M064037; -.
DR HGNC; HGNC:936; BAD.
DR HPA; CAB004205; -.
DR HPA; HPA028185; -.
DR MIM; 603167; gene.
DR neXtProt; NX_Q92934; -.
DR PharmGKB; PA25236; -.
DR eggNOG; NOG43412; -.
DR HOGENOM; HOG000095169; -.
DR HOVERGEN; HBG001653; -.
DR InParanoid; Q92934; -.
DR KO; K02158; -.
DR OMA; GEAGHQQ; -.
DR OrthoDB; EOG7MD4RF; -.
DR PhylomeDB; Q92934; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; BAD; human.
DR EvolutionaryTrace; Q92934; -.
DR GeneWiki; Bcl-2-associated_death_promoter; -.
DR GenomeRNAi; 572; -.
DR NextBio; 2331; -.
DR PMAP-CutDB; Q92934; -.
DR PRO; PR:Q92934; -.
DR ArrayExpress; Q92934; -.
DR Bgee; Q92934; -.
DR CleanEx; HS_BAD; -.
DR Genevestigator; Q92934; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IMP:UniProtKB.
DR GO; GO:0046031; P:ADP metabolic process; ISS:UniProtKB.
DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB.
DR GO; GO:0060154; P:cellular process regulating host cell cycle in response to virus; IEA:Ensembl.
DR GO; GO:0071247; P:cellular response to chromate; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0071396; P:cellular response to lipid; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0071316; P:cellular response to nicotine; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006007; P:glucose catabolic process; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
DR GO; GO:0046931; P:pore complex assembly; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; TAS:UniProtKB.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISS:UniProtKB.
DR GO; GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
DR GO; GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IEA:Ensembl.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:UniProtKB.
DR GO; GO:0043200; P:response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0034201; P:response to oleic acid; IEA:Ensembl.
DR GO; GO:0032570; P:response to progesterone stimulus; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone stimulus; IEA:Ensembl.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; ISS:UniProtKB.
DR InterPro; IPR018868; Bcl-2_BAD.
DR Pfam; PF10514; Bcl-2_BAD; 1.
DR PROSITE; PS01259; BH3; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Complete proteome; Cytoplasm;
KW Membrane; Methylation; Mitochondrion; Mitochondrion outer membrane;
KW Phosphoprotein; Polymorphism; Reference proteome.
FT CHAIN 1 168 Bcl2 antagonist of cell death.
FT /FTId=PRO_0000143103.
FT MOTIF 110 124 BH3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 75 75 Phosphoserine; by PKA, PKB, PIM2, PIM3,
FT PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 and
FT RAF1 (By similarity).
FT MOD_RES 91 91 Phosphoserine.
FT MOD_RES 94 94 Asymmetric dimethylarginine; by PRMT1.
FT MOD_RES 96 96 Asymmetric dimethylarginine; by PRMT1.
FT MOD_RES 99 99 Phosphoserine; by PKA, PKB, PAK1,
FT RPS6KA1, RPS6KB1 and PKC/PRKCQ; alternate
FT (By similarity).
FT MOD_RES 99 99 Phosphoserine; by PKB/AKT1; alternate.
FT MOD_RES 118 118 Phosphoserine.
FT MOD_RES 134 134 Phosphoserine (By similarity).
FT VARIANT 107 107 A -> S (in dbSNP:rs3729933).
FT /FTId=VAR_015380.
FT MUTAGEN 94 94 R->K: Decreased methylation; when
FT associated with K-96.
FT MUTAGEN 96 96 R->K: Decreased methylation; when
FT associated with K-94.
FT HELIX 106 121
SQ SEQUENCE 168 AA; 18392 MW; 69FD8D27DDEE3241 CRC64;
MFQIPEFEPS EQEDSSSAER GLGPSPAGDG PSGSGKHHRQ APGLLWDASH QQEQPTSSSH
HGGAGAVEIR SRHSSYPAGT EDDEGMGEEP SPFRGRSRSA PPNLWAAQRY GRELRRMSDE
FVDSFKKGLP RPKSAGTATQ MRQSSSWTRV FQSWWDRNLG RGSSAPSQ
//
MIM
603167
*RECORD*
*FIELD* NO
603167
*FIELD* TI
*603167 BCL2 ANTAGONIST OF CELL DEATH; BAD
;;BCL2-BINDING PROTEIN; BCL2L8;;
BCL2-BINDING COMPONENT 6
read more*FIELD* TX
DESCRIPTION
Protein interactions among different pro- and antiapoptotic members of
the BCL2 (151430) family are central to their regulation of apoptosis.
These interactions are chiefly influenced by alpha-helical segments
known as BCL2 homology (BH) domains. Some proapoptotic and all
antiapoptotic BCL2 family members share homology within 3 to 4 BH
domains, whereas the BH3-only proapoptotic proteins share homology
within a single BH3 domain. BAD is a BH3-only protein that alternately
functions in apoptosis and metabolism depending upon the availability of
growth factors and nutrients. The switch between apoptotic and metabolic
functions of BAD is controlled by phosphorylation (summary by Danial,
2009).
CLONING
By yeast 2-hybrid screening of a mouse embryonic cDNA fusion library,
Yang et al. (1995) obtained a cDNA encoding a novel Bcl2-binding
protein, termed Bad for 'Bcl2 antagonist of cell death.' The 204-amino
acid murine protein has sequence similarity to members of the BCL2
family within the BH1 and BH2 domains.
Wang et al. (1996) used PCR based on EST sequences to clone a fragment
of the human BAD cDNA.
By searching an EST database for sequences similar to mouse Bad,
followed by screening substantia nigra, bone marrow, and placenta cDNA
libraries, Ottilie et al. (1997) cloned full-length human BAD. The
deduced 168-amino acid protein shares 74% identity with mouse Bad, but
it lacks 42 N-terminal amino acids found in the mouse protein. Ottilie
et al. (1997) noted that the met start codon of human BAD satisfies
Kozak criteria, and that no human BAD variants encoding an N-terminally
extended protein were identified. Alignment of BAD with other BCL2
family proteins revealed a single putative BH3 domain.
GENE FUNCTION
Yang et al. (1995) found that mouse Bad heterodimerized strongly with
Bclx (600039) and less strongly with Bcl2, but it did not bind to other
members of the family. At similar levels of expression, Bad countered
the death repressor activity of Bclx, but not that of Bcl2. Functional
studies revealed that when Bad dimerized with Bclx, it displaced Bax
(600040) and restored its apoptosis-inducing ability. The authors
suggested that BAD may influence the effectiveness of BCL2 versus BCLX
in repressing cell death.
Wang et al. (1996) showed that the human BAD protein was phosphorylated
by the protein kinase RAF1 (164760), which had been targeted by BCL2 to
the mitochondrial membrane.
Using yeast 2-hybrid and solid-phase binding assays, Ottilie et al.
(1997) showed that human BAD dimerized strongly with the long BCLX
isoform (BCLXL) and more weakly with BCL2. BAD did not bind the short
BCLX isoform (BCLXS), BAX, or BAK (600516), and it did not homodimerize.
Competition studies revealed that the BH3 domains of BAD, BCLXL, and
BCL2 were required for heterodimerization. BAD increased the number of
apoptotic cells when transfected into human HEK293 cells, and it
cancelled the prosurvival effect of BCLXL in GM701 human fibroblasts.
Bonni et al. (1999) characterized the mechanism by which the RAS (see
190020)-mitogen-activated protein kinase (MAPK) signaling pathway (see
602448) mediates growth factor-dependent cell survival. The
MAP-activated kinases, the Rsks (see 300075), catalyzed the
phosphorylation of the proapoptotic protein BAD at ser112 both in vitro
and in vivo. The Rsk-induced phosphorylation of BAD at ser112 suppressed
BAD-mediated apoptosis in neurons.
Danial et al. (2003) undertook a proteomic analysis to assess whether
BAD might participate in mitochondrial physiology. In liver
mitochondria, BAD resides in a functional holoenzyme complex together
with protein kinase A (see 176911) and protein phosphatase-1 (PP1; see
176875) catalytic units, WAVE1 (605035) as an A kinase-anchoring
protein, and glucokinase (138079). Using mitochondria from hepatocytes
of Bad-deficient mice, Danial et al. (2003) demonstrated that BAD is
required to assemble the complex, the lack of which results in
diminished mitochondria-based glucokinase activity and blunted
mitochondrial respiration in response to glucose. Glucose deprivation
results in dephosphorylation of BAD, and BAD-dependent cell death.
Moreover, Danial et al. (2003) demonstrated that the phosphorylation
status of BAD helps regulate glucokinase activity. Mice deficient in BAD
or bearing a nonphosphorylatable BAD (3SA) mutant (Datta et al., 2002)
display abnormal glucose homeostasis, including profound defects in
glucose tolerance. Danial et al. (2003) concluded that this combination
of proteomics, genetics, and physiology indicates an unanticipated role
for BAD in integrating pathways of glucose metabolism and apoptosis.
- Reviews
Danial (2009) reviewed the roles of BAD in apoptosis and metabolism, as
well as its regulation by phosphorylation.
MAPPING
Gross (2010) mapped the BAD gene to chromosome 11q13.1 based on an
alignment of the BAD sequence (GenBank GENBANK AB451254) with the
genomic sequence (GRCh37).
ANIMAL MODEL
Ranger et al. (2003) reported that Bad-deficient mice lacking both long
and short Bad proteins were viable, and most cell types appeared to
develop normally. Lymphocytes developed normally with no premalignant
hyperplasia, but they displayed subtle abnormalities in proliferation
and IgG production. Despite the minimal phenotype, Bad-deficient mice
progressed, with aging, to diffuse large B-cell lymphoma of germinal
center origin. Exposure of Bad-null mice to sublethal gamma irradiation
resulted in an increased incidence of pre-T-cell and pro-/pre-B-cell
lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses
tumorigenesis in the lymphocyte lineage.
*FIELD* RF
1. Bonni, A.; Brunet, A.; West, A. E.; Datta, S. R.; Takasu, M. A.;
Greenberg, M. E.: Cell survival promoted by the Ras-MAPK signaling
pathway by transcription-dependent and -independent mechanisms. Science 286:
1358-1362, 1999.
2. Danial, N. N.: BAD: undertaker by night, candyman by day. Oncogene 27:
S53-S70, 2009.
3. Danial, N. N.; Gramm, C. F.; Scorrano, L.; Zhang, C.-Y.; Krauss,
S.; Ranger, A. M.; Datta, S. R.; Greenberg, M. E.; Licklider, L. J.;
Lowell, B. B.; Gygi, S. P.; Korsmeyer, S. J.: BAD and glucokinase
reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424:
952-956, 2003.
4. Datta, S. R.; Ranger, A. M.; Lin, M. Z.; Sturgill, J. F.; Ma, Y.-C.;
Cowan, C. W.; Dikkes, P.; Korsmeyer, S. J.; Greenberg, M. E.: Survival
factor-mediated BAD phosphorylation raises the mitochondrial threshold
for apoptosis. Dev. Cell 3: 631-643, 2002.
5. Gross, M. B.: Personal Communication. Baltimore, Md. 5/10/2010.
6. Ottilie, S.; Diaz, J.-L.; Horne, W.; Chang, J.; Wang, Y.; Wilson,
G.; Chang, S.; Weeks, S.; Fritz, L. C.; Oltersdorf, T.: Dimerization
properties of human BAD: identification of a BH-3 domain and analysis
of its binding to mutant BCL-2 and BCL-X(L) proteins. J. Biol. Chem. 272:
30866-30872, 1997.
7. Ranger, A. M.; Zha, J.; Harada, H.; Datta, S. R.; Danial, N. N.;
Gilmore, A. P.; Kutok, J. L.; Le Beau, M. M.; Greenberg, M. E.; Korsmeyer,
S. J.: Bad-deficient mice develop diffuse large B cell lymphoma. Proc.
Nat. Acad. Sci. 100: 9324-9329, 2003.
8. Wang, H.-G.; Rapp, U. R.; Reed, J. C.: Bcl-2 targets the protein
kinase Raf-1 to mitochondria. Cell 87: 629-638, 1996.
9. Yang, E.; Zha, J.; Jockel, J.; Boise, L. H.; Thompson, C. B.; Korsmeyer,
S. J.: Bad, a heterodimeric partner for Bcl-X(L) and Bcl-2, displaces
Bax and promotes cell death. Cell 80: 285-291, 1995.
*FIELD* CN
Matthew B. Gross - updated: 5/10/2010
Patricia A. Hartz - updated: 12/8/2009
Ada Hamosh - updated: 9/16/2003
Victor A. McKusick - updated: 8/29/2003
Ada Hamosh - updated: 11/11/1999
*FIELD* CD
Jennifer P. Macke: 10/20/1998
*FIELD* ED
carol: 11/29/2012
mgross: 5/10/2010
alopez: 5/7/2010
terry: 12/8/2009
terry: 4/5/2005
alopez: 9/16/2003
tkritzer: 9/4/2003
terry: 8/29/2003
alopez: 11/12/1999
terry: 11/11/1999
alopez: 10/20/1998
*RECORD*
*FIELD* NO
603167
*FIELD* TI
*603167 BCL2 ANTAGONIST OF CELL DEATH; BAD
;;BCL2-BINDING PROTEIN; BCL2L8;;
BCL2-BINDING COMPONENT 6
read more*FIELD* TX
DESCRIPTION
Protein interactions among different pro- and antiapoptotic members of
the BCL2 (151430) family are central to their regulation of apoptosis.
These interactions are chiefly influenced by alpha-helical segments
known as BCL2 homology (BH) domains. Some proapoptotic and all
antiapoptotic BCL2 family members share homology within 3 to 4 BH
domains, whereas the BH3-only proapoptotic proteins share homology
within a single BH3 domain. BAD is a BH3-only protein that alternately
functions in apoptosis and metabolism depending upon the availability of
growth factors and nutrients. The switch between apoptotic and metabolic
functions of BAD is controlled by phosphorylation (summary by Danial,
2009).
CLONING
By yeast 2-hybrid screening of a mouse embryonic cDNA fusion library,
Yang et al. (1995) obtained a cDNA encoding a novel Bcl2-binding
protein, termed Bad for 'Bcl2 antagonist of cell death.' The 204-amino
acid murine protein has sequence similarity to members of the BCL2
family within the BH1 and BH2 domains.
Wang et al. (1996) used PCR based on EST sequences to clone a fragment
of the human BAD cDNA.
By searching an EST database for sequences similar to mouse Bad,
followed by screening substantia nigra, bone marrow, and placenta cDNA
libraries, Ottilie et al. (1997) cloned full-length human BAD. The
deduced 168-amino acid protein shares 74% identity with mouse Bad, but
it lacks 42 N-terminal amino acids found in the mouse protein. Ottilie
et al. (1997) noted that the met start codon of human BAD satisfies
Kozak criteria, and that no human BAD variants encoding an N-terminally
extended protein were identified. Alignment of BAD with other BCL2
family proteins revealed a single putative BH3 domain.
GENE FUNCTION
Yang et al. (1995) found that mouse Bad heterodimerized strongly with
Bclx (600039) and less strongly with Bcl2, but it did not bind to other
members of the family. At similar levels of expression, Bad countered
the death repressor activity of Bclx, but not that of Bcl2. Functional
studies revealed that when Bad dimerized with Bclx, it displaced Bax
(600040) and restored its apoptosis-inducing ability. The authors
suggested that BAD may influence the effectiveness of BCL2 versus BCLX
in repressing cell death.
Wang et al. (1996) showed that the human BAD protein was phosphorylated
by the protein kinase RAF1 (164760), which had been targeted by BCL2 to
the mitochondrial membrane.
Using yeast 2-hybrid and solid-phase binding assays, Ottilie et al.
(1997) showed that human BAD dimerized strongly with the long BCLX
isoform (BCLXL) and more weakly with BCL2. BAD did not bind the short
BCLX isoform (BCLXS), BAX, or BAK (600516), and it did not homodimerize.
Competition studies revealed that the BH3 domains of BAD, BCLXL, and
BCL2 were required for heterodimerization. BAD increased the number of
apoptotic cells when transfected into human HEK293 cells, and it
cancelled the prosurvival effect of BCLXL in GM701 human fibroblasts.
Bonni et al. (1999) characterized the mechanism by which the RAS (see
190020)-mitogen-activated protein kinase (MAPK) signaling pathway (see
602448) mediates growth factor-dependent cell survival. The
MAP-activated kinases, the Rsks (see 300075), catalyzed the
phosphorylation of the proapoptotic protein BAD at ser112 both in vitro
and in vivo. The Rsk-induced phosphorylation of BAD at ser112 suppressed
BAD-mediated apoptosis in neurons.
Danial et al. (2003) undertook a proteomic analysis to assess whether
BAD might participate in mitochondrial physiology. In liver
mitochondria, BAD resides in a functional holoenzyme complex together
with protein kinase A (see 176911) and protein phosphatase-1 (PP1; see
176875) catalytic units, WAVE1 (605035) as an A kinase-anchoring
protein, and glucokinase (138079). Using mitochondria from hepatocytes
of Bad-deficient mice, Danial et al. (2003) demonstrated that BAD is
required to assemble the complex, the lack of which results in
diminished mitochondria-based glucokinase activity and blunted
mitochondrial respiration in response to glucose. Glucose deprivation
results in dephosphorylation of BAD, and BAD-dependent cell death.
Moreover, Danial et al. (2003) demonstrated that the phosphorylation
status of BAD helps regulate glucokinase activity. Mice deficient in BAD
or bearing a nonphosphorylatable BAD (3SA) mutant (Datta et al., 2002)
display abnormal glucose homeostasis, including profound defects in
glucose tolerance. Danial et al. (2003) concluded that this combination
of proteomics, genetics, and physiology indicates an unanticipated role
for BAD in integrating pathways of glucose metabolism and apoptosis.
- Reviews
Danial (2009) reviewed the roles of BAD in apoptosis and metabolism, as
well as its regulation by phosphorylation.
MAPPING
Gross (2010) mapped the BAD gene to chromosome 11q13.1 based on an
alignment of the BAD sequence (GenBank GENBANK AB451254) with the
genomic sequence (GRCh37).
ANIMAL MODEL
Ranger et al. (2003) reported that Bad-deficient mice lacking both long
and short Bad proteins were viable, and most cell types appeared to
develop normally. Lymphocytes developed normally with no premalignant
hyperplasia, but they displayed subtle abnormalities in proliferation
and IgG production. Despite the minimal phenotype, Bad-deficient mice
progressed, with aging, to diffuse large B-cell lymphoma of germinal
center origin. Exposure of Bad-null mice to sublethal gamma irradiation
resulted in an increased incidence of pre-T-cell and pro-/pre-B-cell
lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses
tumorigenesis in the lymphocyte lineage.
*FIELD* RF
1. Bonni, A.; Brunet, A.; West, A. E.; Datta, S. R.; Takasu, M. A.;
Greenberg, M. E.: Cell survival promoted by the Ras-MAPK signaling
pathway by transcription-dependent and -independent mechanisms. Science 286:
1358-1362, 1999.
2. Danial, N. N.: BAD: undertaker by night, candyman by day. Oncogene 27:
S53-S70, 2009.
3. Danial, N. N.; Gramm, C. F.; Scorrano, L.; Zhang, C.-Y.; Krauss,
S.; Ranger, A. M.; Datta, S. R.; Greenberg, M. E.; Licklider, L. J.;
Lowell, B. B.; Gygi, S. P.; Korsmeyer, S. J.: BAD and glucokinase
reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424:
952-956, 2003.
4. Datta, S. R.; Ranger, A. M.; Lin, M. Z.; Sturgill, J. F.; Ma, Y.-C.;
Cowan, C. W.; Dikkes, P.; Korsmeyer, S. J.; Greenberg, M. E.: Survival
factor-mediated BAD phosphorylation raises the mitochondrial threshold
for apoptosis. Dev. Cell 3: 631-643, 2002.
5. Gross, M. B.: Personal Communication. Baltimore, Md. 5/10/2010.
6. Ottilie, S.; Diaz, J.-L.; Horne, W.; Chang, J.; Wang, Y.; Wilson,
G.; Chang, S.; Weeks, S.; Fritz, L. C.; Oltersdorf, T.: Dimerization
properties of human BAD: identification of a BH-3 domain and analysis
of its binding to mutant BCL-2 and BCL-X(L) proteins. J. Biol. Chem. 272:
30866-30872, 1997.
7. Ranger, A. M.; Zha, J.; Harada, H.; Datta, S. R.; Danial, N. N.;
Gilmore, A. P.; Kutok, J. L.; Le Beau, M. M.; Greenberg, M. E.; Korsmeyer,
S. J.: Bad-deficient mice develop diffuse large B cell lymphoma. Proc.
Nat. Acad. Sci. 100: 9324-9329, 2003.
8. Wang, H.-G.; Rapp, U. R.; Reed, J. C.: Bcl-2 targets the protein
kinase Raf-1 to mitochondria. Cell 87: 629-638, 1996.
9. Yang, E.; Zha, J.; Jockel, J.; Boise, L. H.; Thompson, C. B.; Korsmeyer,
S. J.: Bad, a heterodimeric partner for Bcl-X(L) and Bcl-2, displaces
Bax and promotes cell death. Cell 80: 285-291, 1995.
*FIELD* CN
Matthew B. Gross - updated: 5/10/2010
Patricia A. Hartz - updated: 12/8/2009
Ada Hamosh - updated: 9/16/2003
Victor A. McKusick - updated: 8/29/2003
Ada Hamosh - updated: 11/11/1999
*FIELD* CD
Jennifer P. Macke: 10/20/1998
*FIELD* ED
carol: 11/29/2012
mgross: 5/10/2010
alopez: 5/7/2010
terry: 12/8/2009
terry: 4/5/2005
alopez: 9/16/2003
tkritzer: 9/4/2003
terry: 8/29/2003
alopez: 11/12/1999
terry: 11/11/1999
alopez: 10/20/1998