Bcl-2-associated death promoter

BCL2-associated agonist of cell death
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1G5J
Identifiers
Symbols	BAD ; BBC2; BCL2L8
External IDs	OMIM: 603167 MGI: 1096330 HomoloGene: 3189 ChEMBL: 3817 GeneCards: BAD Gene
Gene ontology Molecular function • protein binding • phospholipid binding • lipid binding • cysteine-type endopeptidase activator activity involved in apoptotic process • protein kinase binding • protein phosphatase 2B binding • protein kinase B binding • protein heterodimerization activity Cellular component • mitochondrion • mitochondrial outer membrane • cytosol Biological process • release of cytochrome c from mitochondria • glucose catabolic process • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • epidermal growth factor receptor signaling pathway • fibroblast growth factor receptor signaling pathway • extrinsic apoptotic signaling pathway via death domain receptors • intrinsic apoptotic signaling pathway in response to DNA damage • response to glucose • positive regulation of autophagy • positive regulation of mitochondrial membrane potential • programmed cell death • suppression by virus of host apoptotic process • cytokine-mediated signaling pathway • positive regulation of insulin secretion • response to estradiol • response to progesterone • positive regulation of glucokinase activity • response to testosterone • response to oleic acid • positive regulation of insulin secretion involved in cellular response to glucose stimulus • Fc-epsilon receptor signaling pathway • response to drug • response to hydrogen peroxide • glucose homeostasis • positive regulation of apoptotic process • response to amino acid • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • type B pancreatic cell proliferation • innate immune response • response to ethanol • positive regulation of B cell differentiation • positive regulation of T cell differentiation • positive regulation of proteolysis • negative regulation of cytolysis • ADP metabolic process • ATP metabolic process • regulation of mitochondrial membrane permeability • pore complex assembly • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • positive regulation of epithelial cell proliferation • response to glucocorticoid • response to calcium ion • positive regulation of apoptotic process by virus • cellular process regulating host cell cycle in response to virus • cellular response to chromate • cellular response to mechanical stimulus • cellular response to nicotine • cellular response to lipid • cellular response to hypoxia • positive regulation of release of cytochrome c from mitochondria • apoptotic signaling pathway • extrinsic apoptotic signaling pathway • extrinsic apoptotic signaling pathway in absence of ligand • intrinsic apoptotic signaling pathway • activation of cysteine-type endopeptidase activity • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • positive regulation of neuron death • positive regulation of type B pancreatic cell development • positive regulation of intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE BAD 1861 at tn.png
File:PBB GE BAD 209364 at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	572	12015
Ensembl	ENSG00000002330	ENSMUSG00000024959
UniProt	Q92934	Q61337
RefSeq (mRNA)	NM_004322	NM_001285453
RefSeq (protein)	NP_004313	NP_001272382
Location (UCSC)	Chr 11: 64.27 – 64.28 Mb	Chr 19: 6.94 – 6.95 Mb
PubMed search	[1]	[2]

Pro-apoptotic Bcl-2 protein, BAD
File:PDB 1g5j EBI.jpg complex of bcl-xl with peptide from bad
Identifiers
Symbol	Bcl-2_BAD
Pfam	PF10514
InterPro	IPR018868
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The Bcl-2-associated death promoter (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 , 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. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

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.

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. 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.

Interactions

Overview of signal transduction pathways involved with apoptosis.

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

• BCL2L1,
• BCL2A1,
• BCL2L2,
• Bcl-2,
• MCL1
• S100A10,
• YWHAQ, and
• YWHAZ.

See also

• Programmed cell death

External links

• bcl-Associated Death Protein at the US National Library of Medicine Medical Subject Headings (MeSH)