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Protein

Bcl2-associated agonist of cell death

Gene

Bad

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.

GO - Molecular functioni

  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
  • lipid binding Source: UniProtKB
  • phospholipid binding Source: UniProtKB
  • protein heterodimerization activity Source: MGI
  • protein kinase binding Source: MGI
  • protein phosphatase binding Source: MGI

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: MGI
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • ADP metabolic process Source: UniProtKB
  • apoptotic process Source: MGI
  • apoptotic signaling pathway Source: MGI
  • ATP metabolic process Source: UniProtKB
  • cell proliferation Source: MGI
  • cellular process regulating host cell cycle in response to virus Source: MGI
  • cellular response to chromate Source: Ensembl
  • cellular response to hypoxia Source: Ensembl
  • cellular response to lipid Source: UniProtKB
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to nicotine Source: UniProtKB
  • cellular response to organic substance Source: MGI
  • cytokine-mediated signaling pathway Source: MGI
  • extrinsic apoptotic signaling pathway Source: MGI
  • extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • glucose catabolic process Source: MGI
  • glucose homeostasis Source: UniProtKB
  • intrinsic apoptotic signaling pathway Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
  • negative regulation of cytolysis Source: MGI
  • pore complex assembly Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of apoptotic process by virus Source: MGI
  • positive regulation of B cell differentiation Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of epithelial cell proliferation Source: UniProtKB
  • positive regulation of glucokinase activity Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • positive regulation of mitochondrial membrane potential Source: UniProtKB
  • positive regulation of neuron death Source: Ensembl
  • positive regulation of proteolysis Source: MGI
  • positive regulation of release of cytochrome c from mitochondria Source: MGI
  • positive regulation of T cell differentiation Source: MGI
  • positive regulation of type B pancreatic cell development Source: UniProtKB
  • regulation of apoptotic process Source: MGI
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • regulation of mitochondrial membrane permeability Source: UniProtKB
  • release of cytochrome c from mitochondria Source: MGI
  • response to amino acid Source: Ensembl
  • response to calcium ion Source: Ensembl
  • response to drug Source: Ensembl
  • response to estradiol Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to glucocorticoid Source: Ensembl
  • response to glucose Source: Ensembl
  • response to hydrogen peroxide Source: Ensembl
  • response to oleic acid Source: Ensembl
  • response to progesterone Source: Ensembl
  • response to testosterone Source: Ensembl
  • suppression by virus of host apoptotic process Source: MGI
  • type B pancreatic cell proliferation Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_289095. NRAGE signals death through JNK.
REACT_307563. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
REACT_318722. Activation of BAD and translocation to mitochondria.
REACT_320952. AKT phosphorylates targets in the cytosol.

Names & Taxonomyi

Protein namesi
Recommended name:
Bcl2-associated agonist of cell death
Short name:
BAD
Alternative name(s):
Bcl-2-binding component 6
Bcl-xL/Bcl-2-associated death promoter
Bcl2 antagonist of cell death
Gene namesi
Name:Bad
Synonyms:Bbc6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1096330. Bad.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • mitochondrial outer membrane Source: UniProtKB
  • mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi112 – 1121S → A: Enhances pro-apoptotic activity; no phosphorylation. 2 Publications
Mutagenesisi136 – 1361S → A: No phosphorylation. 1 Publication
Mutagenesisi155 – 1551S → A: Enhances pro-apoptotic activity; no phosphorylation; interacts with Bcl-X(L). 1 Publication
Mutagenesisi155 – 1551S → D: No pro-apoptotic activity, no interaction with Bcl-X(L). 1 Publication
Mutagenesisi170 – 1701S → A: Enhances pro-apoptotic activity. 1 Publication
Mutagenesisi170 – 1701S → D: No pro-apoptotic activity; even when associated with A-112. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 204204Bcl2-associated agonist of cell deathPRO_0000143104Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei112 – 1121Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 AND RAF16 Publications
Modified residuei128 – 1281PhosphoserineBy similarity
Modified residuei131 – 1311Asymmetric dimethylarginine; by PRMT1By similarity
Modified residuei133 – 1331Asymmetric dimethylarginine; by PRMT1By similarity
Modified residuei136 – 1361Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ5 Publications
Modified residuei155 – 1551Phosphoserine; by PKA and PKB1 Publication
Modified residuei170 – 1701Phosphoserine1 Publication

Post-translational modificationi

Phosphorylated on one or more of Ser-112, Ser-136, Ser-155 and Ser-170 in response to survival stimuli, which blocks its pro-apoptotic activity. Phosphorylation on Ser-136 or Ser-112 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-155, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-136 is the major site of AKT/PKB phosphorylation, Ser-155 the major site of protein kinase A (CAPK) phosphorylation.9 Publications
Methylation at Arg-131 and Arg-133 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-136.5 Publications

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ61337.
PaxDbiQ61337.
PRIDEiQ61337.

PTM databases

PhosphoSiteiQ61337.

Miscellaneous databases

PMAP-CutDBQ61337.

Expressioni

Gene expression databases

BgeeiQ61337.
CleanExiMM_BAD.
ExpressionAtlasiQ61337. baseline and differential.
GenevisibleiQ61337. MM.

Interactioni

Subunit structurei

Forms heterodimers with the anti-apoptotic proteins, Bcl-X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity). The Ser-112/Ser-136 phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3 (By similarity). Interacts (via BH3 domain) with NOL3 (via CARD domain); preventing the association of BAD with BCL2 (By similarity). Interacts with HIF3A isoform 2 (via C-terminus domain); the interaction reduces the binding between BAD and BAX (PubMed:21546903).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
BCL2P104156EBI-400328,EBI-77694From a different organism.
BCL2L1Q07817-12EBI-400328,EBI-287195From a different organism.
Bcl2l1Q64373-12EBI-400328,EBI-526380
YWHAZP631043EBI-400328,EBI-347088From a different organism.

Protein-protein interaction databases

BioGridi198296. 4 interactions.
DIPiDIP-273N.
IntActiQ61337. 16 interactions.
MINTiMINT-202237.
STRINGi10090.ENSMUSP00000025910.

Structurei

Secondary structure

1
204
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi139 – 1413Combined sources
Helixi142 – 16019Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BZWX-ray2.30B137-163[»]
DisProtiDP00563.
ProteinModelPortaliQ61337.
SMRiQ61337. Positions 137-163.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61337.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi147 – 16115BH3Add
BLAST

Domaini

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.

Sequence similaritiesi

Belongs to the Bcl-2 family.Curated

Phylogenomic databases

eggNOGiNOG43412.
GeneTreeiENSGT00390000010740.
HOGENOMiHOG000095169.
HOVERGENiHBG001653.
InParanoidiQ61337.
OMAiGEAGHQQ.
OrthoDBiEOG7MD4RF.
PhylomeDBiQ61337.
TreeFamiTF102001.

Family and domain databases

InterProiIPR018868. Bcl-2_BAD.
[Graphical view]
PfamiPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61337-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTPKQPSLA PAHALGLRKS DPGIRSLGSD AGGRRWRPAA QSMFQIPEFE
60 70 80 90 100
PSEQEDASAT DRGLGPSLTE DQPGPYLAPG LLGSNIHQQG RAATNSHHGG
110 120 130 140 150
AGAMETRSRH SSYPAGTEED EGMEEELSPF RGRSRSAPPN LWAAQRYGRE
160 170 180 190 200
LRRMSDEFEG SFKGLPRPKS AGTATQMRQS AGWTRIIQSW WDRNLGKGGS

TPSQ
Length:204
Mass (Da):22,080
Last modified:November 1, 1996 - v1
Checksum:i6C2BA910205053F7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L37296 mRNA. Translation: AAA64465.1.
BC006762 mRNA. Translation: AAH06762.1.
CCDSiCCDS29513.1.
PIRiA55671.
RefSeqiNP_031548.1. NM_007522.3.
UniGeneiMm.4387.

Genome annotation databases

EnsembliENSMUST00000025910; ENSMUSP00000025910; ENSMUSG00000024959.
GeneIDi12015.
UCSCiuc008gjn.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L37296 mRNA. Translation: AAA64465.1.
BC006762 mRNA. Translation: AAH06762.1.
CCDSiCCDS29513.1.
PIRiA55671.
RefSeqiNP_031548.1. NM_007522.3.
UniGeneiMm.4387.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BZWX-ray2.30B137-163[»]
DisProtiDP00563.
ProteinModelPortaliQ61337.
SMRiQ61337. Positions 137-163.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198296. 4 interactions.
DIPiDIP-273N.
IntActiQ61337. 16 interactions.
MINTiMINT-202237.
STRINGi10090.ENSMUSP00000025910.

Chemistry

BindingDBiQ61337.
ChEMBLiCHEMBL5385.

PTM databases

PhosphoSiteiQ61337.

Proteomic databases

MaxQBiQ61337.
PaxDbiQ61337.
PRIDEiQ61337.

Protocols and materials databases

DNASUi12015.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025910; ENSMUSP00000025910; ENSMUSG00000024959.
GeneIDi12015.
UCSCiuc008gjn.2. mouse.

Organism-specific databases

CTDi572.
MGIiMGI:1096330. Bad.

Phylogenomic databases

eggNOGiNOG43412.
GeneTreeiENSGT00390000010740.
HOGENOMiHOG000095169.
HOVERGENiHBG001653.
InParanoidiQ61337.
OMAiGEAGHQQ.
OrthoDBiEOG7MD4RF.
PhylomeDBiQ61337.
TreeFamiTF102001.

Enzyme and pathway databases

ReactomeiREACT_289095. NRAGE signals death through JNK.
REACT_307563. BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members.
REACT_318722. Activation of BAD and translocation to mitochondria.
REACT_320952. AKT phosphorylates targets in the cytosol.

Miscellaneous databases

EvolutionaryTraceiQ61337.
NextBioi280229.
PMAP-CutDBQ61337.
PROiQ61337.
SOURCEiSearch...

Gene expression databases

BgeeiQ61337.
CleanExiMM_BAD.
ExpressionAtlasiQ61337. baseline and differential.
GenevisibleiQ61337. MM.

Family and domain databases

InterProiIPR018868. Bcl-2_BAD.
[Graphical view]
PfamiPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death."
    Yang E., Zha J., Jockel J., Boise L.H., Thompson C.B., Korsmeyer S.J.
    Cell 80:285-291(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain and Thymus.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NMRI.
    Tissue: Mammary gland.
  3. "Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt."
    Del Peso L., Gonzalez-Garcia M., Page C., Herrera R., Nunez G.
    Science 278:687-689(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112 AND SER-136, MUTAGENESIS OF SER-112 AND SER-136.
  4. "Rsk1 mediates a MEK-MAP kinase cell survival signal."
    Shimamura A., Ballif B.A., Richards S.A., Blenis J.
    Curr. Biol. 10:127-135(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112 AND SER-136.
  5. "14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation."
    Datta S.R., Katsov A., Hu L., Petros A., Fesik S.W., Yaffe M.B., Greenberg M.E.
    Mol. Cell 6:41-51(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SERINE RESIDUES.
  6. "p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis."
    Schurmann A., Mooney A.F., Sanders L.C., Sells M.A., Wang H.G., Reed J.C., Bokoch G.M.
    Mol. Cell. Biol. 20:453-461(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112 AND SER-136.
  7. "p21-activated protein kinase gamma-PAK suppresses programmed cell death of BALB3T3 fibroblasts."
    Jakobi R., Moertl E., Koeppel M.A.
    J. Biol. Chem. 276:16624-16634(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112.
  8. "Protein kinase C-theta mediates a selective T cell survival signal via phosphorylation of BAD."
    Villalba M., Bushway P., Altman A.
    J. Immunol. 166:5955-5963(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-136.
  9. "p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD."
    Harada H., Andersen J.S., Mann M., Terada N., Korsmeyer S.J.
    Proc. Natl. Acad. Sci. U.S.A. 98:9666-9670(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-136.
  10. "Identification of a novel phosphorylation site, Ser-170, as a regulator of bad pro-apoptotic activity."
    Dramsi S., Scheid M.P., Maiti A., Hojabrpour P., Chen X., Schubert K., Goodlett D.R., Aebersold R., Duronio V.
    J. Biol. Chem. 277:6399-6405(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-155 AND SER-170, MUTAGENESIS OF SER-112; SER-155 AND SER-170, IDENTIFICATION BY MASS SPECTROMETRY.
  11. "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 P.J., Lilly M.
    J. Biol. Chem. 278:45358-45367(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112 BY PIM2.
  12. "p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association."
    Jin S., Zhuo Y., Guo W., Field J.
    J. Biol. Chem. 280:24698-24705(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-112 BY RAF1.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  14. "Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative regulator of HIF-1, through binding to pro-survival Bcl-2 family proteins."
    Torii S., Goto Y., Ishizawa T., Hoshi H., Goryo K., Yasumoto K., Fukumura H., Sogawa K.
    Cell Death Differ. 18:1711-1725(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HIF3A, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiBAD_MOUSE
AccessioniPrimary (citable) accession number: Q61337
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 22, 2015
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The protein name 'Bcl2 antagonist of cell death' may be misleading. The protein antagonises Bcl2-mediated repression of cell death, hence it promotes apoptosis.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.