BAD phospho S99
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.
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 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.
Post-translational modifications
Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 and 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 interaction then facilitates the phosphorylation at Ser-118, a site within the BH3 motif, leading to the release of Bcl-X(L) and 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. Phosphorylation at Ser-99 by PKB/AKT1 is almost completely blocked by the apoptotic C-terminus cleavage product of PKN2 generated by caspases-3 activity during apoptosis.
Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-99.
Sequence Similarities
Belongs to the Bcl-2 family.
Tissue Specificity
Expressed in a wide variety of tissues.
Cellular localization
- Mitochondrion outer membrane
- Cytoplasm
- Colocalizes with HIF3A in the cytoplasm (By similarity). Upon phosphorylation, locates to the cytoplasm.
Alternative names
BBC6, BCL2L8, BAD, Bcl2-associated agonist of cell death, Bcl-2-binding component 6, Bcl-2-like protein 8, Bcl-xL/Bcl-2-associated death promoter, Bcl2 antagonist of cell death, Bcl2-L-8
Database links
Other research areas
- Immuno-oncology