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Q61337 (BAD_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Bad
Synonyms:Bbc6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length204 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.

Subunit structure

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.

Subcellular location

Mitochondrion outer membrane. Cytoplasm. Note: Upon phosphorylation, locates to the cytoplasm.

Domain

Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.

Post-translational modification

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. Ref.3 Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Methylation at Arg-131 and Arg-133 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-136.

Sequence similarities

Belongs to the Bcl-2 family.

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.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Membrane
Mitochondrion
Mitochondrion outer membrane
   PTMMethylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processADP metabolic process

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

ATP metabolic process

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 19915011. Source: UniProtKB

apoptotic signaling pathway

Inferred from direct assay Ref.10PubMed 15231831. Source: MGI

cell proliferation

Inferred from direct assay PubMed 9176392. Source: MGI

cellular process regulating host cell cycle in response to virus

Inferred from direct assay PubMed 15231831. Source: MGI

cellular response to chromate

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to lipid

Inferred from expression pattern PubMed 18223655. Source: UniProtKB

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to nicotine

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to organic substance

Inferred from sequence orthology PubMed 12727206. Source: MGI

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 14967141. Source: MGI

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 12115603PubMed 12944463. Source: MGI

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from mutant phenotype PubMed 12431371. Source: MGI

glucose catabolic process

Inferred from mutant phenotype PubMed 12931191. Source: MGI

glucose homeostasis

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from direct assay PubMed 15231831. Source: MGI

pore complex assembly

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of B cell differentiation

Inferred from mutant phenotype PubMed 12431371. Source: MGI

positive regulation of T cell differentiation

Inferred from mutant phenotype PubMed 12431371. Source: MGI

positive regulation of apoptotic process

Inferred from direct assay PubMed 21095239. Source: UniProtKB

positive regulation of apoptotic process by virus

Inferred from direct assay PubMed 15231831. Source: MGI

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of glucokinase activity

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

positive regulation of insulin secretion

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

positive regulation of insulin secretion involved in cellular response to glucose stimulus

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

positive regulation of mitochondrial membrane potential

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

positive regulation of neuron death

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

positive regulation of release of cytochrome c from mitochondria

Inferred from electronic annotation. Source: Ensembl

positive regulation of type B pancreatic cell development

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

regulation of apoptotic process

Inferred from direct assay Ref.1. Source: MGI

regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 14967141. Source: MGI

regulation of mitochondrial membrane permeability

Inferred from sequence or structural similarity. Source: UniProtKB

release of cytochrome c from mitochondria

Inferred from mutant phenotype PubMed 12431371. Source: MGI

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

response to oleic acid

Inferred from electronic annotation. Source: Ensembl

response to progesterone

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

suppression by virus of host apoptotic process

Inferred from direct assay PubMed 15231831. Source: MGI

type B pancreatic cell proliferation

Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11146504. Source: MGI

cytosol

Inferred from direct assay PubMed 11980919. Source: MGI

mitochondrial outer membrane

Inferred from sequence or structural similarity. Source: UniProtKB

mitochondrion

Inferred from direct assay PubMed 12931191PubMed 18614015. Source: MGI

   Molecular_functioncysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from direct assay PubMed 19915011. Source: UniProtKB

lipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

phospholipid binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 18223655PubMed 19915011PubMed 21095239. Source: UniProtKB

protein heterodimerization activity

Inferred from physical interaction Ref.1. Source: MGI

protein phosphatase binding

Inferred from physical interaction PubMed 12944463. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 204204Bcl2-associated agonist of cell death
PRO_0000143104

Regions

Motif147 – 16115BH3

Amino acid modifications

Modified residue1121Phosphoserine; by PKA, PKB, PIM2, PIM3, PAK1, PAK2, PAK4, PAK7/PAK5, RPS6KA1 AND RAF1 Ref.3 Ref.4 Ref.6 Ref.7 Ref.11 Ref.12
Modified residue1281Phosphoserine By similarity
Modified residue1311Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue1331Asymmetric dimethylarginine; by PRMT1 By similarity
Modified residue1361Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ Ref.3 Ref.4 Ref.6 Ref.8 Ref.9
Modified residue1551Phosphoserine; by PKA and PKB Probable
Modified residue1701Phosphoserine Ref.10

Experimental info

Mutagenesis1121S → A: Enhances pro-apoptotic activity; no phosphorylation. Ref.3 Ref.5 Ref.10
Mutagenesis1361S → A: No phosphorylation. Ref.3 Ref.5
Mutagenesis1551S → A: Enhances pro-apoptotic activity; no phosphorylation; interacts with Bcl-X(L). Ref.5 Ref.10
Mutagenesis1551S → D: No pro-apoptotic activity, no interaction with Bcl-X(L). Ref.5 Ref.10
Mutagenesis1701S → A: Enhances pro-apoptotic activity. Ref.5 Ref.10
Mutagenesis1701S → D: No pro-apoptotic activity; even when associated with A-112. Ref.5 Ref.10

Secondary structure

.... 204
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61337 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 6C2BA910205053F7

FASTA20422,080
        10         20         30         40         50         60 
MGTPKQPSLA PAHALGLRKS DPGIRSLGSD AGGRRWRPAA QSMFQIPEFE PSEQEDASAT 

        70         80         90        100        110        120 
DRGLGPSLTE DQPGPYLAPG LLGSNIHQQG RAATNSHHGG AGAMETRSRH SSYPAGTEED 

       130        140        150        160        170        180 
EGMEEELSPF RGRSRSAPPN LWAAQRYGRE LRRMSDEFEG SFKGLPRPKS AGTATQMRQS 

       190        200 
AGWTRIIQSW WDRNLGKGGS TPSQ 

« Hide

References

« Hide 'large scale' references
[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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L37296 mRNA. Translation: AAA64465.1.
BC006762 mRNA. Translation: AAH06762.1.
CCDSCCDS29513.1.
PIRA55671.
RefSeqNP_031548.1. NM_007522.3.
UniGeneMm.4387.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BZWX-ray2.30B137-163[»]
DisProtDP00563.
ProteinModelPortalQ61337.
SMRQ61337. Positions 137-163.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198296. 4 interactions.
DIPDIP-273N.
IntActQ61337. 16 interactions.
MINTMINT-202237.

Chemistry

BindingDBQ61337.
ChEMBLCHEMBL5385.

PTM databases

PhosphoSiteQ61337.

Proteomic databases

PaxDbQ61337.
PRIDEQ61337.

Protocols and materials databases

DNASU12015.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025910; ENSMUSP00000025910; ENSMUSG00000024959.
GeneID12015.
KEGGmmu:12015.
UCSCuc008gjn.1. mouse.

Organism-specific databases

CTD572.
MGIMGI:1096330. Bad.

Phylogenomic databases

eggNOGNOG43412.
GeneTreeENSGT00390000010740.
HOGENOMHOG000095169.
HOVERGENHBG001653.
InParanoidQ61337.
KOK02158.
OMAGEAGHQQ.
OrthoDBEOG7MD4RF.
PhylomeDBQ61337.
TreeFamTF102001.

Gene expression databases

ArrayExpressQ61337.
BgeeQ61337.
CleanExMM_BAD.
GenevestigatorQ61337.

Family and domain databases

InterProIPR018868. Bcl-2_BAD.
[Graphical view]
PfamPF10514. Bcl-2_BAD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ61337.
NextBio280229.
PMAP-CutDBQ61337.
PROQ61337.
SOURCESearch...

Entry information

Entry nameBAD_MOUSE
AccessionPrimary (citable) accession number: Q61337
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot