| Description | 168 amino acids, 18,4 kDa.; 'BH3 only' Bcl2 family member (do not possess BH1, 2 and 4 domains). The BH3 domain is essential for proapoptotic function. There is structural similarities between the Bcl2 family proteins and bacterial toxins which form membrane pores after oligomerisation. Do not possess a transmembrane domain in COOH term, in contrast with a number of other BCL2 family members; may be phosphorylated on serine residues (see below). |
| Expression | wide |
| Localisation | cytoplasm vs membrane of the mitochondria (see below) |
| Function | Proapoptotic protein:
In its inactive form, Bad is phosphorylated. Proteins which phosphorylate BAD are: RAF1, ribosomal S6 kinase 1 (p90/RSK1), AKT/PKB (PI3K-AKT pathway) at Serine 136 (in murine BAD), PKA at Ser 155, PIM1and PIM2 at Ser 112 (Ser 75, 99, and 118 in human BAD correspond to Ser 112, 136, and 155 in murine BAD respectively). Phosphorylated BAD interacts with 14-3-3 scaffold proteins in the cytoplasm (14-3-3 is a protein which can interact with a hundred other proteins). Cleavage of the 14-3-3 protein by caspase-3 allows the release of BAD from its association with the 14-3-3 protein and facilitates BAD translocation from the cytosol to the mitochondria. Under apoptotic stimuli also, calcineurin (Ca++ activated protein phosphatase) dephosphorylates BAD, also allowing its dissociation from 14-3-3. Once BAD is dephosphorylated (posttranslational modification), it is active; it translocates to the outer membrane of the mitochondria (like other proapototic members of the Bcl2 family), and forms heterodimers with BCL-XL (and, to a lesser extend, heterodimers with BCL2 or BCL2L2) to block BCL-XL antiapoptotic function. Dimers BCL-XL /BAD are similar to dimers BCL-XL /BAK |
| Homology | Bcl2 family members:
The antiapoptotic members with BH 1 to 4 domains: BCL2 (18q21), BCL1L1/BCLX-L ID: n129> (20q11), BCL2L2/BCL-W (14q11), BCL1L10/BCL-B/BOO/DIVA (15q21), BCL2A1/BFL1/A1 (15q24), BNIP1/EIB-19K (5q33), MCL1 (1q21) HOMOLOGY The proapoptotic members with BH 1 to 3 domains: BAK1/BCL2L7 (6p21), BAX (19q13), (22q11), (2q37) The only-BH3 apoptotic members: BBC3/PUMA (19q13), BCL2L11/BIM/BOD (2q13), BID (22q11), BIK/NBK/BBC1 (22q13), BLK (8p23), BMF (15q14), BNIP3/NIP3 (10q26), BMIP3L/NIX (8p21), HRK/DP5/BID3 (12q24), PMAIP1/NOXA (18q21) |
| Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. |
| Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ |
| Cell. 1995 ; 80 (2) : 285-291. |
| PMID 7834748 |
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| Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins. |
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| PMID 9388232 |
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| Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. |
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| PMID 9381178 |
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| Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. |
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| PMID 9372935 |
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| Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. |
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| PMID 10195903 |
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| PMID 10949026 |
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| PMID 12239175 |
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| PMID 11878929 |
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| PMID 12965220 |
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| PMID 14996494 |
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| PMID 14996500 |
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| PMID 14996501 |
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