Bcl2 antagonist of cell death - Mus musculus (Mouse)

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Q61337 (BAD_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified December 11, 2013. Version 115. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Bcl2 antagonist of cell death
Short name=BAD

Alternative name(s):
Bcl-2-binding component 6
Bcl-xL/Bcl-2-associated death promoter

Gene names

Name:	Bad
Synonyms:	Bbc6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	204 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ADP metabolic process Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB ATP metabolic process Inferred from mutant phenotype PubMed 18223655. Source: UniProtKB cellular process regulating host cell cycle in response to virus Inferred from direct assay PubMed 15231831. Source: MGI 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 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 12115603 PubMed 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 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 by virus Inferred from direct assay PubMed 15231831. Source: MGI 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 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 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 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 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_component	cytosol Inferred from direct assay PubMed 11980919. Source: MGI mitochondrial outer membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	cysteine-type endopeptidase activator activity involved in apoptotic process Inferred from direct assay PubMed 19915011. Source: UniProtKB phospholipid binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	6	EBI-400328,EBI-77694	From a different organism.
BCL2L1	Q07817-1	2	EBI-400328,EBI-287195	From a different organism.
Bcl2l1	Q64373-1	2	EBI-400328,EBI-526380
YWHAZ	P63104	3	EBI-400328,EBI-347088	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 204

204

Bcl2 antagonist of cell death

PRO_0000143104

Regions

Motif

147 – 161

BH3

Amino acid modifications

Modified residue

112

Phosphoserine; 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 residue

128

Phosphoserine By similarity

Modified residue

131

Asymmetric dimethylarginine; by PRMT1 By similarity

Modified residue

133

Asymmetric dimethylarginine; by PRMT1 By similarity

Modified residue

136

Phosphoserine; by PKA, PKB, PAK1, RPS6KA1, RPS6KB1 and PKC/PRKCQ Ref.3 Ref.4 Ref.6 Ref.8 Ref.9

Modified residue

155

Phosphoserine; by PKA and PKB

Modified residue

170

Phosphoserine Ref.10

Experimental info

Mutagenesis

112

S → A: Enhances pro-apoptotic activity; no phosphorylation. Ref.3 Ref.5 Ref.10

Mutagenesis

136

S → A: No phosphorylation. Ref.3 Ref.5

Mutagenesis

155

S → A: Enhances pro-apoptotic activity; no phosphorylation; interacts with Bcl-X(L). Ref.5 Ref.10

Mutagenesis

155

S → D: No pro-apoptotic activity, no interaction with Bcl-X(L). Ref.5 Ref.10

Mutagenesis

170

S → A: Enhances pro-apoptotic activity. Ref.5 Ref.10

Mutagenesis

170

S → D: No pro-apoptotic activity; even when associated with A-112. Ref.5 Ref.10

Secondary structure

204

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q61337 [UniParc].

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

FASTA

204

22,080

        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' referencesShow '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-170, MUTAGENESIS OF SER-112; SER-155 AND SER-170, 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.

IPI

IPI00119986.

PIR

A55671.

RefSeq

NP_031548.1. NM_007522.3.

UniGene

Mm.4387.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BZW	X-ray	2.30	B	137-163	[»]

DisProt

DP00563.

ProteinModelPortal

Q61337.

SMR

Q61337. Positions 137-163.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-273N.

IntAct

Q61337. 16 interactions.

MINT

MINT-202237.

Chemistry

BindingDB

Q61337.

ChEMBL

CHEMBL5385.

PTM databases

PhosphoSite

Q61337.

Proteomic databases

PaxDb

Q61337.

PRIDE

Q61337.

Protocols and materials databases

DNASU

12015.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000025910; ENSMUSP00000025910; ENSMUSG00000024959.

GeneID

12015.

KEGG

mmu:12015.

UCSC

uc008gjn.1. mouse.

Organism-specific databases

CTD

572.

MGI

MGI:1096330. Bad.

Phylogenomic databases

eggNOG

NOG43412.

GeneTree

ENSGT00390000010740.

HOGENOM

HOG000095169.

HOVERGEN

HBG001653.

InParanoid

Q61337.

K02158.

OMA

GEAGHQQ.

OrthoDB

EOG7MD4RF.

Gene expression databases

ArrayExpress

Q61337.

Bgee

Q61337.

CleanEx

MM_BAD.

Genevestigator

Q61337.

Family and domain databases

InterPro

IPR018868. Bcl-2_BAD.
[Graphical view]

Pfam

PF10514. Bcl-2_BAD. 1 hit.
[Graphical view]

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q61337.

NextBio

280229.

PMAP-CutDB

Q61337.

PRO

Q61337.

SOURCE

Search...

Entry information

Entry name

BAD_MOUSE

Accession

Primary (citable) accession number: Q61337

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	December 11, 2013
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents