BAD (Homo sapiens)

Description [+]

Synonyms: BAD, BCL2L8, BBC2
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Bcl2 antagonist of cell death (BAD)(Bcl-2-binding component 6)(Bcl-XL/Bcl-2-associated death promoter)(Bcl-2-like 8 protein) [Source:UniProtKB/Swiss-Prot;Acc:Q92934]
Family: Bcl-2 family : BH3-only
Process: apoptosis,
Pathways: intrinsic pathway, pre-mitochondrial signaling events,
Criteria: manually curated
Curator comment: The murine counterpart for Bad participates in regulation of glucose metabolism
Mouse ortholog(s): Bad
WIKI: BAD-H_sapiens

References [+]

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
To extend the mammalian cell death pathway, we screened for further Bcl-2 interacting proteins. Both yeast two-hybrid screening and lambda expression cloning identified a novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains. Bad selectively dimerized with Bcl-xL as well as Bcl-2, but not with Bax, Bcl-xs, Mcl-1, A1, or itself. Bad binds more strongly to Bcl-xL than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-xL, but not that of Bcl-2. When Bad dimerized with Bcl-xL, Bax was displaced and apoptosis was restored. When approximately half of Bax was heterodimerized, death was inhibited. The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death. Cell. 1995 Jan 27;80(2):285-91.

References from Mouse ortholog(s):

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
The Bcl-2 related protein Bad is a promoter of apoptosis and has been shown to dimerize with the anti-apoptotic proteins Bcl-2 and Bcl-XL. Overexpression of Bad in murine FL5.12 cells demonstrated that the protein not only could abrogate the protective capacity of coexpressed Bcl-XL but could accelerate the apoptotic response to a death signal when it was expressed in the absence of exogenous Bcl-XL. Using deletion analysis, we have identified the minimal domain in the murine Bad protein that can dimerize with Bcl-xL. A 26-amino-acid peptide within this domain, which showed significant homology to the alpha-helical BH3 domains of related apoptotic proteins like Bak and Bax, was found to be necessary and sufficient to bind Bcl-xL. To determine the role of dimerization in regulating the death-promoting activity of Bad and the death-inhibiting activity of Bcl-xL, mutations within the hydrophobic BH3-binding pocket in Bcl-xL that eliminated the ability of Bcl-xL to form a heterodimer with Bad were tested for the ability to promote cell survival in the presence of Bad. Several of these mutants retained the ability to impart protection against cell death regardless of the level of coexpressed Bad protein. These results suggest that BH3-containing proteins like Bad promote cell death by binding to antiapoptotic members of the Bcl-2 family and thus inhibiting their survival promoting functions. Mol Cell Biol. 1997 Dec;17(12):7040-6.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Bcl-2_BAD	1	168

Evolution [+]

Name	Relationship	Species
BAD	orthology	Chimpanzee
NP_001030536.1	orthology	Cow
Q45KI9_CANFA	orthology	Dog
BAD	orthology	Fugu
BAD	orthology	Gasterosteus
BAD	orthology	Gorilla
BAD	orthology	Horse
BAD	orthology	Macaca
BAD	orthology	Medaka
Bad	orthology	Mouse
BAD	orthology	Orangutan
BAD	orthology	Rabbit
Bad_v2	orthology	Rat
BAD	orthology	Tetraodon
bad	orthology	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0008633	activation of pro-apoptotic gene products	biological_proccess	EXP
GO:0006917	induction of apoptosis	biological_proccess	NAS
GO:0006915	apoptosis	biological_proccess	IEA
GO:0042981	regulation of apoptosis	biological_proccess	IEA
GO:0006917	induction of apoptosis	biological_proccess	IEA
GO:0008283	cell proliferation	biological_proccess	IEA
GO:0042593	glucose homeostasis	biological_proccess	IEA
GO:0019221	cytokine-mediated signaling pathway	biological_proccess	IEA
GO:0008624	induction of apoptosis by extracellular signals	biological_proccess	IEA
GO:0045582	positive regulation of T cell differentiation	biological_proccess	IEA
GO:0045579	positive regulation of B cell differentiation	biological_proccess	IEA
GO:0043281	regulation of caspase activity	biological_proccess	IEA
GO:0006007	glucose catabolic process	biological_proccess	IEA
GO:0005515	protein binding	mollecular_function	NAS
GO:0005515	protein binding	mollecular_function	IEA
GO:0005741	mitochondrial outer membrane	cell_component	EXP
GO:0005829	cytosol	cell_component	EXP
GO:0005739	mitochondrion	cell_component	IEA
GO:0016020	membrane	cell_component	IEA
GO:0005737	cytoplasm	cell_component	NAS
GO:0005737	cytoplasm	cell_component	IEA
GO:0005829	cytosol	cell_component	IEA

Check GO Evidence Codes here

KEGG Pathways [+]

KEGG report for BAD: 572

KEGG pathways for BAD:

hsa01510: Neurodegenerative Diseases (entry, map)

hsa04012: ErbB signaling pathway (entry, map)

hsa04210: Apoptosis (entry, map)

hsa04370: VEGF signaling pathway (entry, map)

hsa04510: Focal adhesion (entry, map)

hsa04910: Insulin signaling pathway (entry, map)

hsa05030: Amyotrophic lateral sclerosis (ALS) (entry, map)

hsa05210: Colorectal cancer (entry, map)

hsa05212: Pancreatic cancer (entry, map)

hsa05213: Endometrial cancer (entry, map)

hsa05215: Prostate cancer (entry, map)

hsa05218: Melanoma (entry, map)

hsa05220: Chronic myeloid leukemia (entry, map)

hsa05221: Acute myeloid leukemia (entry, map)

hsa05223: Non-small cell lung cancer (entry, map)

Curated Isoforms [+]

Transcript	Translation
OTTHUMT00000259179	OTTHUMP00000165928
OTTHUMT00000259180 *	OTTHUMP00000165929 *
OTTHUMT00000259181	OTTHUMP00000165930
OTTHUMT00000259182
OTTHUMT00000259183

Information from other databases [+]

Gene related links:

Gene info from HGNC [?] :936
Gene related info from GeneCards [?] : BAD
Ensembl genome browser [?] : ENSG00000002330
Expression info from Arrayexpress [?] : ENSG00000002330
Protein expression from Protein Atlas: [?] ENSG00000002330
Community gene edition from Wikigenes: [?] 572

Protein related links:

Uniprot protein info: Q92934
PIR protein info: Q92934
Protein interactions from IntAct: Q92934

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 603167
OMIM disease information:

Other links

entrezgene: 572
refseq_dna: NM_032989
refseq_dna: NM_004322
refseq_peptide: NP_116784
refseq_peptide: NP_004313

Click on [?] for more information.