BAD (タンパク質)

利用可能な蛋白質構造:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Pro-apoptotic Bcl-2 protein, BAD
	Bad由来ペプチドとBcl-xLの複合体
識別子
略号	Bcl-2_BAD
Pfam	PF10514
InterPro	IPR018868
利用可能な蛋白質構造:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
	テンプレートを表示

BAD
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1G5J
識別子
記号	BAD, BBC2, BCL2L8, BCL2 associated agonist of cell death
外部ID	OMIM: 603167 MGI: 1096330 HomoloGene: 3189 GeneCards: BAD
遺伝子の位置 (ヒト)
染色体	11番染色体 (ヒト)
終点	64,284,704 bp
遺伝子の位置 (マウス)
染色体	19番染色体 (マウス)
終点	6,929,267 bp
RNA発現パターン
	; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• 14-3-3 protein binding; • protein phosphatase binding; • 血漿タンパク結合; • protein heterodimerization activity; • cysteine-type endopeptidase activator activity involved in apoptotic process; • phospholipid binding; • プロテインキナーゼ結合; • 脂質結合; • protein phosphatase 2B binding; • protein kinase B binding;
細胞の構成要素	• 細胞質; • 細胞質基質; • 膜; • ミトコンドリア外膜; • ミトコンドリア;
生物学的プロセス	• positive regulation of T cell differentiation; • cellular response to hypoxia; • regulation of apoptotic process; • response to amino acid; • エストラジオールへの反応; • 低酸素症への反応; • positive regulation of type B pancreatic cell development; • 有機環状化合物への反応; • extrinsic apoptotic signaling pathway; • positive regulation of autophagy; • glucose homeostasis; • サイトカイン媒介シグナル伝達経路; • response to testosterone; • positive regulation of epithelial cell proliferation; • positive regulation of B cell differentiation; • response to progesterone; • positive regulation of apoptotic process by virus; • pore complex assembly; • cellular response to nicotine; • 糖質コルチコイドへの反応; • positive regulation of neuron death; • response to glucose; • regulation of cysteine-type endopeptidase activity involved in apoptotic process; • 有機物への反応; • response to calcium ion; • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; • ATP metabolic process; • cellular response to mechanical stimulus; • activation of cysteine-type endopeptidase activity; • regulation of mitochondrial membrane permeability; • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • positive regulation of intrinsic apoptotic signaling pathway; • positive regulation of glucokinase activity; • 精子形成; • glucose catabolic process; • intrinsic apoptotic signaling pathway in response to DNA damage; • positive regulation of proteolysis; • 大脳皮質発生; • extrinsic apoptotic signaling pathway in absence of ligand; • cellular response to lipid; • positive regulation of release of cytochrome c from mitochondria; • ホルモンへの反応; • positive regulation of mitochondrial membrane potential; • positive regulation of insulin secretion involved in cellular response to glucose stimulus; • suppression by virus of host apoptotic process; • response to ethanol; • ADP metabolic process; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • 細胞増殖; • type B pancreatic cell proliferation; • cellular response to chromate; • extrinsic apoptotic signaling pathway via death domain receptors; • 過酸化水素への反応; • response to oleic acid; • release of cytochrome c from mitochondria; • positive regulation of insulin secretion; • アポトーシス; • intrinsic apoptotic signaling pathway; • apoptotic signaling pathway; • protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • positive regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; • positive regulation of apoptotic process; • positive regulation of granulosa cell apoptotic process;
	出典:Amigo / QuickGO
オルソログ
	572
	12015
	ENSG00000002330
	ENSMUSG00000024959
	Q92934
	Q61337
	NM_032989; NM_004322
	NM_007522; NM_001285453
	NP_004313; NP_116784
	NP_001272382; NP_031548
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

BAD（BCL2 associated agonist of cell death）^[5]はBcl-2ファミリーのアポトーシス促進性のメンバーであり、アポトーシスの開始に関与している。BADはBcl-２ファミリーの中でも、BH3-onlyファミリーのメンバーである^[6]。BADは他の多くのBcl-2ファミリーのメンバーと異なり、ミトコンドリア外膜や核膜への標的化を行うC末端の膜貫通ドメインを持たない^[7]。活性化後は、抗アポトーシスタンパク質とヘテロ二量体を形成することで、それらによるアポトーシスの停止を防ぐ。

作用機序

Bax/Bakはミトコンドリア外膜にポアを形成してシトクロムcを細胞質へ放出し、アポトーシスを促進するカスパーゼカスケードを活性化することでアポトーシスを開始すると考えられている。抗アポトーシスタンパク質であるBcl-2やBcl-xLはミトコンドリアのポアを介したシトクロムcの放出を阻害し、またシトクロムcによる細胞質でのカスパーゼカスケードの活性化も阻害する^[8]。

非リン酸化状態のBadはBcl-2やBcl-xLとヘテロ二量体を形成し、これらを不活性化してBax/Bakによるアポトーシスの開始を可能にする。BadはAkt/プロテインキナーゼBによるリン酸化（PIP₃によって開始される）を受けると、14-3-3タンパク質とヘテロ二量体を形成する。これによってBcl-2はBaxによるアポトーシスを阻害できるようになる^[8]。このように、Badのリン酸化は抗アポトーシス作用を持ち、Badの脱リン酸化（Ca²⁺によって刺激されたカルシニューリンによるものなど）はアポトーシス促進作用を持つ。後者は統合失調症などの神経疾患にも関与している可能性がある^[9]。

相互作用

BADは次に挙げる因子と相互作用することが示されている

BCL2^[10]^[11]
BCL2A1（英語版）^[10]^[12]
BCL2L1（英語版）^[10]^[13]^[14]^[15]^[16]^[17]^[11]^[18]^[19]^[20]^[21]
BCL2L2（英語版）^[10]^[16]^[12]^[22]
MCL1（英語版）^[10]^[12]
S100A10（英語版）^[23]
YWHAQ（英語版）^[10]^[23]
YWHAZ^[24]

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000002330 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024959 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “BAD BCL2 associated agonist of cell death [Homo sapiens (Human)] - Gene - NCBI”. 2021年10月18日閲覧。
^ “The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2”. Cell Death Differ. 9 (11): 1240–7. (2002). doi:10.1038/sj.cdd.4401097. PMID 12404123.
^ “Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11”. Mol. Endocrinol. 11 (12): 1858–67. (1997). doi:10.1210/me.11.12.1858. PMID 9369453.
^ ^a ^b Helmreich, E. J. M. (2001). The biochemistry of cell signalling. Oxford: Oxford University Press. pp. 238-243. ISBN 0-19-850820-4. OCLC 45743304
^ Foster, T. C.; Sharrow, K. M.; Masse, J. R.; Norris, C. M.; Kumar, A. (2001-06-01). “Calcineurin links Ca2+ dysregulation with brain aging”. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 21 (11): 4066–4073. doi:10.1523/JNEUROSCI.21-11-04066.2001. ISSN 1529-2401. PMC 1201477. PMID 11356894.
^ ^a ^b ^c ^d ^e ^f “Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function”. Mol. Cell 17 (3): 393–403. (February 2005). doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
^ ^a ^b “Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death”. Cell 80 (2): 285–91. (January 1995). doi:10.1016/0092-8674(95)90411-5. PMID 7834748.
^ ^a ^b ^c “Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis”. Apoptosis 6 (5): 319–30. (October 2001). doi:10.1023/A:1011319901057. PMID 11483855.
^ “Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase”. J. Biol. Chem. 280 (16): 16045–52. (April 2005). doi:10.1074/jbc.M413488200. PMID 15705582.
^ “BAD partly reverses paclitaxel resistance in human ovarian cancer cells”. Oncogene 17 (19): 2419–27. (November 1998). doi:10.1038/sj.onc.1202180. PMID 9824152.
^ “Development of a high-throughput fluorescence polarization assay for Bcl-x(L)”. Anal. Biochem. 307 (1): 70–5. (August 2002). doi:10.1016/S0003-2697(02)00028-3. PMID 12137781.
^ ^a ^b “The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad”. Eur. J. Immunol. 32 (7): 1847–55. (July 2002). doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
^ “Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis”. Nat. Cell Biol. 2 (1): 1–6. (January 2000). doi:10.1038/71316. PMID 10620799.
^ “Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies”. Protein Sci. 9 (12): 2528–34. (Dec 2000). doi:10.1110/ps.9.12.2528. PMC 2144516. PMID 11206074.
^ “BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest”. Oncogene 20 (33): 4507–18. (July 2001). doi:10.1038/sj.onc.1204584. PMID 11494146.
^ “Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy”. Nature 390 (6658): 413–7. (November 1997). Bibcode: 1997Natur.390..413I. doi:10.1038/37144. PMID 9389483.
^ “PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition”. Oncogene 19 (46): 5291–7. (November 2000). doi:10.1038/sj.onc.1203901. PMID 11077446.
^ “Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members”. Cell Death Differ. 6 (6): 525–32. (June 1999). doi:10.1038/sj.cdd.4400519. PMID 10381646.
^ ^a ^b “Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11”. Mol. Endocrinol. 11 (12): 1858–67. (November 1997). doi:10.1210/me.11.12.1858. PMID 9369453.
^ “The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta”. Biochim. Biophys. Acta 1547 (2): 313–9. (June 2001). doi:10.1016/S0167-4838(01)00202-3. PMID 11410287.

外部リンク

bcl-Associated Death Protein - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
Human BAD genome location and BAD gene details page in the UCSC Genome Browser.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000002330 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000024959 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[:0-5] “BAD BCL2 associated agonist of cell death [Homo sapiens (Human)] - Gene - NCBI”. 2021年10月18日閲覧。

[adachi-6] “The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2”. Cell Death Differ. 9 (11): 1240–7. (2002). doi:10.1038/sj.cdd.4401097. PMID 12404123.

[sheau-7] “Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11”. Mol. Endocrinol. 11 (12): 1858–67. (1997). doi:10.1210/me.11.12.1858. PMID 9369453.

[:1-8] Helmreich, E. J. M. (2001). The biochemistry of cell signalling. Oxford: Oxford University Press. pp. 238-243. ISBN 0-19-850820-4. OCLC 45743304

[9] Foster, T. C.; Sharrow, K. M.; Masse, J. R.; Norris, C. M.; Kumar, A. (2001-06-01). “Calcineurin links Ca2+ dysregulation with brain aging”. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 21 (11): 4066–4073. doi:10.1523/JNEUROSCI.21-11-04066.2001. ISSN 1529-2401. PMC 1201477. PMID 11356894.

[pmid15694340-10] ^ ^a ^b ^c ^d ^e ^f “Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function”. Mol. Cell 17 (3): 393–403. (February 2005). doi:10.1016/j.molcel.2004.12.030. PMID 15694340.

[pmid7834748-11] “Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death”. Cell 80 (2): 285–91. (January 1995). doi:10.1016/0092-8674(95)90411-5. PMID 7834748.

[pmid11483855-12] “Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis”. Apoptosis 6 (5): 319–30. (October 2001). doi:10.1023/A:1011319901057. PMID 11483855.

[pmid15705582-13] “Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase”. J. Biol. Chem. 280 (16): 16045–52. (April 2005). doi:10.1074/jbc.M413488200. PMID 15705582.

[pmid9824152-14] “BAD partly reverses paclitaxel resistance in human ovarian cancer cells”. Oncogene 17 (19): 2419–27. (November 1998). doi:10.1038/sj.onc.1202180. PMID 9824152.

[pmid12137781-15] “Development of a high-throughput fluorescence polarization assay for Bcl-x(L)”. Anal. Biochem. 307 (1): 70–5. (August 2002). doi:10.1016/S0003-2697(02)00028-3. PMID 12137781.

[pmid12115603-16] “The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad”. Eur. J. Immunol. 32 (7): 1847–55. (July 2002). doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.

[pmid10620799-17] “Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis”. Nat. Cell Biol. 2 (1): 1–6. (January 2000). doi:10.1038/71316. PMID 10620799.

[pmid11206074-18] “Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies”. Protein Sci. 9 (12): 2528–34. (Dec 2000). doi:10.1110/ps.9.12.2528. PMC 2144516. PMID 11206074.

[pmid11494146-19] “BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest”. Oncogene 20 (33): 4507–18. (July 2001). doi:10.1038/sj.onc.1204584. PMID 11494146.

[pmid9389483-20] “Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy”. Nature 390 (6658): 413–7. (November 1997). Bibcode: 1997Natur.390..413I. doi:10.1038/37144. PMID 9389483.

[pmid11077446-21] “PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition”. Oncogene 19 (46): 5291–7. (November 2000). doi:10.1038/sj.onc.1203901. PMID 11077446.

[pmid10381646-22] “Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members”. Cell Death Differ. 6 (6): 525–32. (June 1999). doi:10.1038/sj.cdd.4400519. PMID 10381646.

[pmid9369453-23] “Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11”. Mol. Endocrinol. 11 (12): 1858–67. (November 1997). doi:10.1210/me.11.12.1858. PMID 9369453.

[pmid11410287-24] “The proapoptotic protein Bad binds the amphipathic groove of 14-3-3zeta”. Biochim. Biophys. Acta 1547 (2): 313–9. (June 2001). doi:10.1016/S0167-4838(01)00202-3. PMID 11410287.

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BAD (タンパク質)

作用機序

相互作用

出典

関連文献

関連項目

外部リンク