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MT000068

UniProt Annotations

Entry Information

Gene Name	BCL2-associated agonist of cell death
Protein Entry	BAD_HUMAN
UniProt ID	Q92934
Species	Human

Comments

Comment type	Description
Caution	The protein name 'Bcl2 antagonist of cell death' may be misleading. The protein antagonises Bcl2-mediated repression of cell death, hence it promotes apoptosis. {ECO:0000305}.
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. {ECO:0000250}.
Interaction	P10415:BCL2; NbExp=5; IntAct=EBI-700771, EBI-77694; Q07817:BCL2L1; NbExp=4; IntAct=EBI-700771, EBI-78035; Q07817-1:BCL2L1; NbExp=6; IntAct=EBI-700771, EBI-287195; O43521:BCL2L11; NbExp=2; IntAct=EBI-700771, EBI-526406; O60238:BNIP3L; NbExp=2; IntAct=EBI-700771, EBI-849893; P45983:MAPK8; NbExp=2; IntAct=EBI-700771, EBI-286483; P03495:NS (xeno); NbExp=2; IntAct=EBI-700771, EBI-2548993; P04049:RAF1; NbExp=2; IntAct=EBI-700771, EBI-365996; P31947:SFN; NbExp=4; IntAct=EBI-700771, EBI-476295; P17361:VACWR028 (xeno); NbExp=2; IntAct=EBI-700771, EBI-7115640; P63104:YWHAZ; NbExp=5; IntAct=EBI-700771, EBI-347088;
Ptm	Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt- mediated phosphorylation at Ser-99. {ECO:0000269\|PubMed:10926925, ECO:0000269\|PubMed:21444773}.
Ptm	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. {ECO:0000269\|PubMed:10926925, ECO:0000269\|PubMed:11278822, ECO:0000269\|PubMed:12897128, ECO:0000269\|PubMed:16818649, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:19690332}.
Sequence Caution	Sequence=AAB36516.1; Type=Frameshift; Positions=64, 91; Evidence={ECO:0000305};
Similarity	Belongs to the Bcl-2 family. {ECO:0000305}.
Subcellular Location	Mitochondrion outer membrane. Cytoplasm. Note=Upon phosphorylation, locates to the cytoplasm.
Subunit	Forms heterodimers with the anti-apoptotic proteins, Bcl- X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity). The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins (By similarity). Interacts with AKT1 and PIM3. {ECO:0000250, ECO:0000269\|PubMed:10926925, ECO:0000269\|PubMed:17270021}.
Tissue Specificity	Expressed in a wide variety of tissues.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BADID130ch11q13.html";
Web Resource	Name=Wikipedia; Note=Bcl 2-associated death promoter entry; URL="http://en.wikipedia.org/wiki/Bcl-2-associated_death_promoter";