Bad is a member of the Bcl2 family and acts to promote apoptosis by forming heterodimers with the survival proteins Bcl2 and BclxL, thus preventing them from binding with BAX. Bad is found on the outer mitochondrial membrane and, once phosphorylated in response to growth stimuli, translocates to the cytoplasm. The phosphorylation status of Bad represents a key checkpoint for death or cell survival. JNK-induced phosphorylation of BAD serine 128 promotes the apoptotic role of Bad by opposing the inhibitory effect of growth factor on Bad-mediated apoptosis. Cdc2-induced phosphorylation of Bad serine 128 has an inhibitory effect on its interaction with 14-3-3 proteins. The latter interaction is critical for Bad phosphorylation at serine 155, a site within the BH3 domain that leads to the release of BclxL and the promotion of cell survival. Alternative splicing of this gene results in two transcript variants which encode the same isoform.
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. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.
Subunit : Forms heterodimers with the anti-apoptotic proteins, Bcl-X（L）, Bcl-2 and Bcl-W. Also binds protein S100A10. The Ser-75/Ser-99 phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3.
Subcellular Location : Mitochondrion outer membrane. Cytoplasm. Note=Upon phosphorylation, locates to the cytoplasm.
Tissue Specificity : Expressed in a wide variety of tissues.
Post-translational modifications : Phosphorylated on one or more of Ser-75, Ser-99, Ser-118 andSer-134 in response to survival stimuli, which blocks itspro-apoptotic activity. Phosphorylation on Ser-99 or Ser-75promotes heterodimerization with 14-3-3 proteins. This interactionthen facilitates the phosphorylation at Ser-118, a site within theBH3 motif, leading to the release of Bcl-X（L） and the promotion ofcell 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 compley blockedby the apoptotic C-terminus cleavage product of PKN2 generated bycaspases-3 activity during apoptosis. 
Methylation at Arg-94 and Arg-96 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-99.
Similarity : Belongs to the Bcl-2 family.
Database links : UniProtKB/Swiss-Prot: Q92934.3
BAD是BCL2/BAX、BCL-XL/BAX異二聚體的負(fù)調(diào)節(jié)基因。BAD是BCL2/BCL-XL相關(guān)死亡促進(jìn)因子，作為BCL2、 bCL-XL異二聚體伴分子而促進(jìn)細(xì)胞凋亡。
有學(xué)者認(rèn)為：BAD缺乏典型的羧基端跨膜結(jié)構(gòu)，提示其并非一完整膜蛋白。與同BCL2作用相比，BAD與BCL-XL的結(jié)合更強(qiáng)，BAD以濃度依賴性方式替換BCL-XL/BAX、BCL2/BAX異二聚體中的BAX，使BAX游離而促進(jìn)細(xì)胞凋亡。當(dāng)一細(xì)胞系的所有細(xì)胞內(nèi)異二聚體（BCL-XL/BAX和BCL2/BAX）的含量≥50%時，則細(xì)胞耐受凋亡；而當(dāng)細(xì)胞內(nèi)BAX同二聚體＞80%時且在適當(dāng)信號誘導(dǎo)下則細(xì)胞出現(xiàn)凋亡。這表明BAD通過調(diào)節(jié)BAX同二聚體與異二聚體量的比值而介導(dǎo)凋亡。