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Bcl2 antagonist of cell death; BAD; Bcl-2-binding component 6; Bcl-2-like protein 8; Bcl2-L-8; Bcl-XL/Bcl-2-associated death promoter (BAD, BBC6, BCL2L8)

Function: - promotes apoptosis - competes for binding to Bcl-XL, Bcl-2 & Bcl-W, thus affecting the level of heterodimerization of these proteins with BAX. - can reverse death repressor activity of Bcl-XL, but not that of Bcl-2 - appears to act as a link between growth factor receptor signaling & the apoptotic pathways - phosphorylated on one or more of Ser-75, Ser-99, Ser-118 & Ser-134 in response to survival stimuli, which blocks its pro-apoptotic activity - phosphorylation on Ser-99 or Ser-75 promotes heterodimerization with 14-3-3 proteins; this then facilitates phosphorylation at Ser-118, a site within the BH3 domain, leading to the release of Bcl-XL & the promotion of cell survival - Ser-99 is the major site of AKT/PKB phosphorylation, Ser-118 the major site of protein kinase A (CAPK) phosphorylation (putative) - phosphorylation at Ser-112 by raf1 kinase or ribosomal S6 kinase - forms heterodimers with the anti-apoptotic proteins, Bcl-XL, Bcl-2 & Bcl-W - also binds protein S100A10 (putative) - the Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins Structure: - intact BH3 motif is required by BIK, BID, BAK, BAD & BAX for their pro-apoptotic activity & for their interaction with anti-apoptotic members of the Bcl-2 family - belongs to the Bcl-2 family Compartment: - mitochondrial outer membrane, cytoplasm - upon phosphorylation, locates to the cytoplasm Expression: expressed in a wide variety of tissues

Interactions

molecular events

General

BH3 subfamily protein phosphoprotein pro apoptotic protein

Properties

SIZE: entity length = 168 aa MW = 18 kD COMPARTMENT: mitochondria cytoplasm MOTIF: Ser phosphorylation site {S75} Ser phosphorylation site {S99} BH3 domain NAME: BH3 domain SITE: 110-124 MOTIF: Ser phosphorylation site {S118} Ser phosphorylation site {S134}

References

  1. UniProt :accession Q92934
  2. OMIM :accession Q92934
  3. Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 2001 Jan;26(1):61-6. Review. PMID: 11165519
  4. Entrez Gene :accession 572
  5. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/BADID130ch11q13.html
  6. Wikipedia; Note: Bcl 2-associated death promoter entry http://en.wikipedia.org/wiki/Bcl-2-associated_death_promoter

Component-of

molecular complex

Databases & Figures

OMIM 603167 UniProt Q92934 Pfam PF10514 Entrez Gene 572 KEGG correlations Figures/diagrams/slides/tables related to Bcl2 antagonist of cell death