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BAD (BCL2-antagonist of cell death)

Written2004-08Jean-Loup Huret, Sylvie Senon
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

Other namesBAD (BCLXL/BCL2 associated death promoter homolog
BBC2
BCL2L8 (Bcl-2-like 8 protein)
HGNC (Hugo) BAD
LocusID (NCBI) 572
Atlas_Id 130
Location 11q13.1
Location_base_pair Starts at 64037300 and ends at 64052176 bp from pter ( according to hg19-Feb_2009)  [Mapping BAD.png]
Fusion genes
(updated 2016)
BAD (11q13.1) / BAD (11q13.1)FAU (11q13.1) / BAD (11q13.1)KLK6 (19q13.41) / BAD (11q13.1)
PLCB3 (11q13.1) / BAD (11q13.1)

DNA/RNA

Description The gene spans 14,9 kb, on reverse strand
Transcription alternate splicing encoding for the same protein

Protein

Description 168 amino acids, 18,4 kDa.; 'BH3 only' Bcl2 family member (do not possess BH1, 2 and 4 domains). The BH3 domain is essential for proapoptotic function. There is structural similarities between the Bcl2 family proteins and bacterial toxins which form membrane pores after oligomerisation. Do not possess a transmembrane domain in COOH term, in contrast with a number of other BCL2 family members; may be phosphorylated on serine residues (see below).
Expression wide
Localisation cytoplasm vs membrane of the mitochondria (see below)
Function Proapoptotic protein:
  • In its inactive form, Bad is phosphorylated. Proteins which phosphorylate BAD are: RAF1, ribosomal S6 kinase 1 (p90/RSK1), AKT/PKB (PI3K-AKT pathway) at Serine 136 (in murine BAD), PKA at Ser 155, PIM1and PIM2 at Ser 112 (Ser 75, 99, and 118 in human BAD correspond to Ser 112, 136, and 155 in murine BAD respectively). Phosphorylated BAD interacts with 14-3-3 scaffold proteins in the cytoplasm (14-3-3 is a protein which can interact with a hundred other proteins).
  • Cleavage of the 14-3-3 protein by caspase-3 allows the release of BAD from its association with the 14-3-3 protein and facilitates BAD translocation from the cytosol to the mitochondria. Under apoptotic stimuli also, calcineurin (Ca++ activated protein phosphatase) dephosphorylates BAD, also allowing its dissociation from 14-3-3.
  • Once BAD is dephosphorylated (posttranslational modification), it is active; it translocates to the outer membrane of the mitochondria (like other proapototic members of the Bcl2 family), and forms heterodimers with BCL-XL (and, to a lesser extend, heterodimers with BCL2 or BCL2L2) to block BCL-XL antiapoptotic function. Dimers BCL-XL /BAD are similar to dimers BCL-XL /BAK
  • Homology Bcl2 family members:
  • The antiapoptotic members with BH 1 to 4 domains: BCL2 (18q21), BCL1L1/BCLX-L ID: n129> (20q11), BCL2L2/BCL-W (14q11), BCL1L10/BCL-B/BOO/DIVA (15q21), BCL2A1/BFL1/A1 (15q24), BNIP1/EIB-19K (5q33), (1q21)
  • The proapoptotic members with BH 1 to 3 domains: BAK1/BCL2L7 (6p21), BAX (19q13), BCL2L13/BCL-Rambo/MIL1 ID: n236> (22q11), (2q37)
  • The only-BH3 apoptotic members: BBC3/PUMA (19q13), BCL2L11/BIM/BOD (2q13), BID (22q11), BIK/NBK/BBC1 (22q13), BLK (8p23), BMF (15q14), BNIP3/NIP3 (10q26), BMIP3L/NIX (8p21), HRK/DP5/BID3 (12q24), PMAIP1/NOXA (18q21)
  • Bibliography

    Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death.
    Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ
    Cell. 1995 ; 80 (2) : 285-291.
    PMID 7834748
     
    Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins.
    Ottilie S, Diaz JL, Horne W, Chang J, Wang Y, Wilson G, Chang S, Weeks S, Fritz LC, Oltersdorf T
    The Journal of biological chemistry. 1997 ; 272 (49) : 30866-30872.
    PMID 9388232
     
    Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.
    del Peso L, Gonz´lez-Garcí M, Page C, Herrera R, Nuñez G
    Science (New York, N.Y.). 1997 ; 278 (5338) : 687-689.
    PMID 9381178
     
    Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL.
    Kelekar A, Chang BS, Harlan JE, Fesik SW, Thompson CB
    Molecular and cellular biology. 1997 ; 17 (12) : 7040-7046.
    PMID 9372935
     
    Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.
    Wang HG, Pathan N, Ethell IM, Krajewski S, Yamaguchi Y, Shibasaki F, McKeon F, Bobo T, Franke TF, Reed JC
    Science (New York, N.Y.). 1999 ; 284 (5412) : 339-343.
    PMID 10195903
     
    14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.
    Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB, Greenberg ME
    Molecular cell. 2000 ; 6 (1) : 41-51.
    PMID 10949026
     
    Role of PI3-kinase-dependent Bad phosphorylation and altered transcription in cytokine-mediated neutrophil survival.
    Cowburn AS, Cadwallader KA, Reed BJ, Farahi N, Chilvers ER
    Blood. 2002 ; 100 (7) : 2607-2616.
    PMID 12239175
     
    Induction of Bad-mediated apoptosis by Sindbis virus infection: involvement of pro-survival members of the Bcl-2 family.
    Moriishi K, Koura M, Matsuura Y
    Virology. 2002 ; 292 (2) : 258-271.
    PMID 11878929
     
    Mutation of BAD within the BH3 domain impairs its phosphorylation-mediated regulation.
    Adachi M, Zhang YB, Imai K
    FEBS letters. 2003 ; 551 (1-3) : 147-152.
    PMID 12965220
     
    The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death.
    Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ, Lilly M
    The Journal of biological chemistry. 2003 ; 278 (46) : 45358-45367.
    PMID 12954615
     
    Cleavage of 14-3-3 protein by caspase-3 facilitates bad interaction with Bcl-x(L) during apoptosis.
    Won J, Kim DY, La M, Kim D, Meadows GG, Joe CO
    The Journal of biological chemistry. 2003 ; 278 (21) : 19347-19351.
    PMID 12657644
     
    Structural biology of the Bcl-2 family of proteins.
    Petros AM, Olejniczak ET, Fesik SW
    Biochimica et biophysica acta. 2004 ; 1644 (2-3) : 83-94.
    PMID 14996493
     
    Bcl-2 family members: integrators of survival and death signals in physiology and pathology [corrected].
    Schinzel A, Kaufmann T, Borner C
    Biochimica et biophysica acta. 2004 ; 1644 (2-3) : 95-105.
    PMID 14996494
     
    Control of proliferation by Bcl-2 family members.
    Bonnefoy-Berard N, Aouacheria A, Verschelde C, Quemeneur L, Marçais A, Marvel J
    Biochimica et biophysica acta. 2004 ; 1644 (2-3) : 159-168.
    PMID 14996500
     
    Bcl-2 family members and disease.
    Sorenson CM
    Biochimica et biophysica acta. 2004 ; 1644 (2-3) : 169-177.
    PMID 14996501
     

    Citation

    This paper should be referenced as such :
    Huret, JL ; Senon, S
    BAD (BCL2-antagonist of cell death)
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(4):276-277.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/BADID130ch11q13.html


    External links

    Nomenclature
    HGNC (Hugo)BAD   936
    Cards
    AtlasBADID130ch11q13
    Entrez_Gene (NCBI)BAD  572  BCL2 associated agonist of cell death
    AliasesBBC2; BCL2L8
    GeneCards (Weizmann)BAD
    Ensembl hg19 (Hinxton)ENSG00000002330 [Gene_View]  chr11:64037300-64052176 [Contig_View]  BAD [Vega]
    Ensembl hg38 (Hinxton)ENSG00000002330 [Gene_View]  chr11:64037300-64052176 [Contig_View]  BAD [Vega]
    ICGC DataPortalENSG00000002330
    TCGA cBioPortalBAD
    AceView (NCBI)BAD
    Genatlas (Paris)BAD
    WikiGenes572
    SOURCE (Princeton)BAD
    Genomic and cartography
    GoldenPath hg19 (UCSC)BAD  -     chr11:64037300-64052176 -  11q13.1   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)BAD  -     11q13.1   [Description]    (hg38-Dec_2013)
    EnsemblBAD - 11q13.1 [CytoView hg19]  BAD - 11q13.1 [CytoView hg38]
    Mapping of homologs : NCBIBAD [Mapview hg19]  BAD [Mapview hg38]
    OMIM603167   
    Gene and transcription
    Genbank (Entrez)AB451254 AB451378 AF021792 AF031523 AK023420
    RefSeq transcript (Entrez)NM_004322 NM_032989
    RefSeq genomic (Entrez)NC_000011 NC_018922 NT_167190 NW_004929380
    Consensus coding sequences : CCDS (NCBI)BAD
    Cluster EST : UnigeneHs.370254 [ NCBI ]
    CGAP (NCI)Hs.370254
    Alternative Splicing GalleryENSG00000002330
    Gene ExpressionBAD [ NCBI-GEO ]   BAD [ EBI - ARRAY_EXPRESS ]   BAD [ SEEK ]   BAD [ MEM ]
    Gene Expression Viewer (FireBrowse)BAD [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)572
    GTEX Portal (Tissue expression)BAD
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ92934 (Uniprot)
    NextProtQ92934  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ92934
    Splice isoforms : SwissVarQ92934 (Swissvar)
    PhosPhoSitePlusQ92934
    Domains : Interpro (EBI)BAD   
    Domain families : Pfam (Sanger)Bcl-2_BAD (PF10514)   
    Domain families : Pfam (NCBI)pfam10514   
    DMDM Disease mutations572
    Blocks (Seattle)BAD
    PDB (SRS)1G5J   
    PDB (PDBSum)1G5J   
    PDB (IMB)1G5J   
    PDB (RSDB)1G5J   
    Structural Biology KnowledgeBase1G5J   
    SCOP (Structural Classification of Proteins)1G5J   
    CATH (Classification of proteins structures)1G5J   
    SuperfamilyQ92934
    Human Protein AtlasENSG00000002330
    Peptide AtlasQ92934
    HPRD04409
    IPIIPI00024291   IPI01012371   IPI00793228   IPI01011886   IPI01009237   
    Protein Interaction databases
    DIP (DOE-UCLA)Q92934
    IntAct (EBI)Q92934
    FunCoupENSG00000002330
    BioGRIDBAD
    STRING (EMBL)BAD
    ZODIACBAD
    Ontologies - Pathways
    QuickGOQ92934
    Ontology : AmiGOrelease of cytochrome c from mitochondria  protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  protein binding  phospholipid binding  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  cytosol  cytosol  glucose catabolic process  apoptotic process  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  spermatogenesis  lipid binding  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of autophagy  positive regulation of mitochondrial membrane potential  suppression by virus of host apoptotic process  cytokine-mediated signaling pathway  protein kinase binding  cerebral cortex development  protein phosphatase 2B binding  positive regulation of insulin secretion  response to estradiol  response to progesterone  positive regulation of glucokinase activity  response to testosterone  response to oleic acid  positive regulation of insulin secretion involved in cellular response to glucose stimulus  response to drug  response to hydrogen peroxide  glucose homeostasis  positive regulation of apoptotic process  positive regulation of apoptotic process  positive regulation of apoptotic process  response to amino acid  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein kinase B binding  type B pancreatic cell proliferation  response to ethanol  positive regulation of B cell differentiation  positive regulation of T cell differentiation  positive regulation of proteolysis  negative regulation of cytolysis  ADP metabolic process  ATP metabolic process  regulation of mitochondrial membrane permeability  pore complex assembly  protein heterodimerization activity  positive regulation of epithelial cell proliferation  response to glucocorticoid  response to calcium ion  positive regulation of apoptotic process by virus  cellular process regulating host cell cycle in response to virus  cellular response to chromate  cellular response to mechanical stimulus  cellular response to nicotine  cellular response to lipid  cellular response to hypoxia  14-3-3 protein binding  positive regulation of release of cytochrome c from mitochondria  extrinsic apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  intrinsic apoptotic signaling pathway  activation of cysteine-type endopeptidase activity  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  positive regulation of neuron death  positive regulation of type B pancreatic cell development  positive regulation of intrinsic apoptotic signaling pathway  
    Ontology : EGO-EBIrelease of cytochrome c from mitochondria  protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  protein binding  phospholipid binding  mitochondrion  mitochondrial outer membrane  mitochondrial outer membrane  cytosol  cytosol  glucose catabolic process  apoptotic process  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  spermatogenesis  lipid binding  extrinsic apoptotic signaling pathway via death domain receptors  intrinsic apoptotic signaling pathway in response to DNA damage  cysteine-type endopeptidase activator activity involved in apoptotic process  response to glucose  positive regulation of autophagy  positive regulation of mitochondrial membrane potential  suppression by virus of host apoptotic process  cytokine-mediated signaling pathway  protein kinase binding  cerebral cortex development  protein phosphatase 2B binding  positive regulation of insulin secretion  response to estradiol  response to progesterone  positive regulation of glucokinase activity  response to testosterone  response to oleic acid  positive regulation of insulin secretion involved in cellular response to glucose stimulus  response to drug  response to hydrogen peroxide  glucose homeostasis  positive regulation of apoptotic process  positive regulation of apoptotic process  positive regulation of apoptotic process  response to amino acid  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  protein kinase B binding  type B pancreatic cell proliferation  response to ethanol  positive regulation of B cell differentiation  positive regulation of T cell differentiation  positive regulation of proteolysis  negative regulation of cytolysis  ADP metabolic process  ATP metabolic process  regulation of mitochondrial membrane permeability  pore complex assembly  protein heterodimerization activity  positive regulation of epithelial cell proliferation  response to glucocorticoid  response to calcium ion  positive regulation of apoptotic process by virus  cellular process regulating host cell cycle in response to virus  cellular response to chromate  cellular response to mechanical stimulus  cellular response to nicotine  cellular response to lipid  cellular response to hypoxia  14-3-3 protein binding  positive regulation of release of cytochrome c from mitochondria  extrinsic apoptotic signaling pathway  extrinsic apoptotic signaling pathway in absence of ligand  intrinsic apoptotic signaling pathway  activation of cysteine-type endopeptidase activity  positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway  positive regulation of neuron death  positive regulation of type B pancreatic cell development  positive regulation of intrinsic apoptotic signaling pathway  
    Pathways : BIOCARTARole of nicotinic acetylcholine receptors in the regulation of apoptosis [Genes]    AKT Signaling Pathway [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation [Genes]    Phosphoinositides and their downstream targets. [Genes]    Ras Signaling Pathway [Genes]    Ceramide Signaling Pathway [Genes]    Apoptotic Signaling in Response to DNA Damage [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    Regulation of BAD phosphorylation [Genes]   
    Pathways : KEGGErbB signaling pathway    Ras signaling pathway    PI3K-Akt signaling pathway    Apoptosis    VEGF signaling pathway    Focal adhesion    Neurotrophin signaling pathway    Insulin signaling pathway    Thyroid hormone signaling pathway    Alzheimer's disease    Amyotrophic lateral sclerosis (ALS)    Toxoplasmosis    Tuberculosis    Hepatitis C    Hepatitis B    Pathways in cancer    Viral carcinogenesis    Colorectal cancer    Pancreatic cancer    Endometrial cancer    Prostate cancer    Melanoma    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
    REACTOMEQ92934 [protein]
    REACTOME PathwaysR-HSA-111447 Activation of BAD and translocation to mitochondria [pathway]
    REACTOME PathwaysR-HSA-193648 NRAGE signals death through JNK [pathway]
    REACTOME PathwaysR-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer [pathway]
    REACTOME PathwaysR-HSA-111453 BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members [pathway]
    REACTOME PathwaysR-HSA-198323 AKT phosphorylates targets in the cytosol [pathway]
    NDEx Network
    Atlas of Cancer Signalling NetworkBAD
    Wikipedia pathwaysBAD
    Orthology - Evolution
    OrthoDB572
    GeneTree (enSembl)ENSG00000002330
    Phylogenetic Trees/Animal Genes : TreeFamBAD
    Homologs : HomoloGeneBAD
    Homology/Alignments : Family Browser (UCSC)BAD
    Gene fusions - Rearrangements
    Fusion : MitelmanPLCB3/BAD [11q13.1/11q13.1]  [t(11;11)(q13;q13)]  
    Fusion: TCGAPLCB3 11q13.1 BAD 11q13.1 BRCA
    Polymorphisms : SNP, variants
    NCBI Variation ViewerBAD [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)BAD
    dbVarBAD
    ClinVarBAD
    1000_GenomesBAD 
    Exome Variant ServerBAD
    ExAC (Exome Aggregation Consortium)BAD (select the gene name)
    Genetic variants : HAPMAP572
    Genomic Variants (DGV)BAD [DGVbeta]
    Mutations
    ICGC Data PortalBAD 
    TCGA Data PortalBAD 
    Broad Tumor PortalBAD
    OASIS PortalBAD [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICBAD 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
    BioMutasearch BAD
    DgiDB (Drug Gene Interaction Database)BAD
    DoCM (Curated mutations)BAD (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)BAD (select a term)
    intoGenBAD
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)11:64037300-64052176  ENSG00000002330
    CONAN: Copy Number AnalysisBAD 
    Mutations and Diseases : HGMDBAD
    OMIM603167   
    MedgenBAD
    Genetic Testing Registry BAD
    NextProtQ92934 [Medical]
    TSGene572
    GENETestsBAD
    Huge Navigator BAD [HugePedia]
    snp3D : Map Gene to Disease572
    BioCentury BCIQBAD
    ClinGenBAD
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD572
    Chemical/Pharm GKB GenePA25236
    Clinical trialBAD
    Miscellaneous
    canSAR (ICR)BAD (select the gene name)
    Probes
    Litterature
    PubMed240 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineBAD
    EVEXBAD
    GoPubMedBAD
    iHOPBAD
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Sat May 28 11:29:51 CEST 2016

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