Bcl-2-associated death promoter

The BCL2 associated agonist of cell death^[5] (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family,^[6] a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family.^[7] After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

BAD
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1G5J
Identifiers
Aliases	BAD, BBC2, BCL2L8, BCL2 associated agonist of cell death
External IDs	OMIM: 603167; MGI: 1096330; HomoloGene: 3189; GeneCards: BAD; OMA:BAD - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q13.1 Start 64,269,830 bp[1] End 64,284,704 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 A Start 6,919,229 bp[2] End 6,929,267 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon right frontal lobe right auricle of heart apex of heart body of stomach C1 segment olfactory zone of nasal mucosa right coronary artery muscle layer of sigmoid colon left coronary artery Top expressed in blastocyst internal carotid artery external carotid artery lip facial motor nucleus duodenum right kidney pyloric antrum granulocyte morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function 14-3-3 protein binding protein phosphatase binding protein binding protein heterodimerization activity cysteine-type endopeptidase activator activity involved in apoptotic process phospholipid binding protein kinase binding lipid binding protein phosphatase 2B binding protein kinase B binding Cellular component cytoplasm cytosol membrane mitochondrial outer membrane mitochondrion Biological process positive regulation of T cell differentiation cellular response to hypoxia regulation of apoptotic process response to amino acid response to estradiol response to hypoxia positive regulation of type B pancreatic cell development response to organic cyclic compound extrinsic apoptotic signaling pathway positive regulation of autophagy glucose homeostasis cytokine-mediated signaling pathway response to testosterone positive regulation of epithelial cell proliferation positive regulation of B cell differentiation response to progesterone positive regulation of apoptotic process by virus pore complex assembly cellular response to nicotine response to glucocorticoid positive regulation of neuron death response to glucose regulation of cysteine-type endopeptidase activity involved in apoptotic process response to organic substance response to calcium ion positive regulation of cysteine-type endopeptidase activity involved in apoptotic process ATP metabolic process cellular response to mechanical stimulus activation of cysteine-type endopeptidase activity regulation of mitochondrial membrane permeability positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway positive regulation of intrinsic apoptotic signaling pathway positive regulation of glucokinase activity spermatogenesis glucose catabolic process intrinsic apoptotic signaling pathway in response to DNA damage positive regulation of proteolysis cerebral cortex development extrinsic apoptotic signaling pathway in absence of ligand cellular response to lipid positive regulation of release of cytochrome c from mitochondria response to hormone positive regulation of mitochondrial membrane potential positive regulation of insulin secretion involved in cellular response to glucose stimulus suppression by virus of host apoptotic process response to ethanol ADP metabolic process activation of cysteine-type endopeptidase activity involved in apoptotic process cell population proliferation type B pancreatic cell proliferation cellular response to chromate extrinsic apoptotic signaling pathway via death domain receptors response to hydrogen peroxide response to oleic acid release of cytochrome c from mitochondria positive regulation of insulin secretion apoptotic process intrinsic apoptotic signaling pathway apoptotic signaling pathway protein insertion into mitochondrial membrane involved in apoptotic signaling pathway positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress positive regulation of apoptotic process positive regulation of granulosa cell apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 572 12015 Ensembl ENSG00000002330 ENSMUSG00000024959 UniProt Q92934 Q61337 RefSeq (mRNA) NM_032989 NM_004322 NM_007522 NM_001285453 RefSeq (protein) NP_004313 NP_116784 NP_001272382 NP_031548 Location (UCSC) Chr 11: 64.27 – 64.28 Mb Chr 19: 6.92 – 6.93 Mb PubMed search [3] [4]
Wikidata
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Pro-apoptotic Bcl-2 protein, BAD
complex of bcl-xl with peptide from bad
Identifiers
Symbol	Bcl-2_BAD
Pfam	PF10514
InterPro	IPR018868
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Mechanism of action

Bax/Bak are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c.^[8]

Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivating them and thus allowing Bax/Bak-triggered apoptosis. When BAD is phosphorylated by Akt/protein kinase B (triggered by PIP₃), it forms the BAD-(14-3-3) protein heterodimer. This leaves Bcl-2 free to inhibit Bax-triggered apoptosis.^[9] BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca²⁺-stimulated Calcineurin) is pro-apoptotic. The latter may be involved in neural diseases such as schizophrenia.^[10]

Interactions

Overview of signal transduction pathways involved with apoptosis.

Bcl-2-associated death promoter has been shown to interact with:

• BCL2L1^{[11][12][13][14][15][16][17][18][19][20][21]}
• BCL2A1^[11][22]
• BCL2L2^{[11][15][22][23]}
• Bcl-2^[11][17]
• MCL1^[11][22]
• S100A10^[24]
• YWHAQ^[11][24] and
• YWHAZ^[25]

See also

• Programmed cell death