BCL2L11

BCL2L11（BCL2 like 11）またはBim（Bcl-2 interacting mediator of cell death）は、ヒトではBCL2L11遺伝子によってコードされているタンパク質である^[5][6]。

BCL2L11
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 1F95, 2K7W, 2NL9, 2V6Q, 2VM6, 2WH6, 2YQ6, 2YQ7, 3D7V, 3FDL, 3IO8, 3IO9, 3KJ0, 3KJ1, 3KJ2, 4A1U, 4A1W, 4B4S, 4D2M, 4QVF, 4UF3, 4YJ4, 4ZIF, 4ZIH, 5AGW, 5AGX, 5C3G
識別子
記号	BCL2L11, BAM, BIM, BOD, BCL2 like 11
外部ID	OMIM: 603827 MGI: 1197519 HomoloGene: 7643 GeneCards: BCL2L11
遺伝子の位置 (ヒト) 染色体 2番染色体 (ヒト)[1] バンド データ無し 開始点 111,119,378 bp[1] 終点 111,168,445 bp[1]
遺伝子の位置 (マウス) 染色体 2番染色体 (マウス)[2] バンド データ無し 開始点 127,967,958 bp[2] 終点 128,004,467 bp[2]
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 • 血漿タンパク結合 • microtubule binding • dynein complex binding • protein heterodimerization activity • プロテインキナーゼ結合 細胞の構成要素 • 細胞質 • 細胞質基質 • 膜 • intracellular membrane-bounded organelle • BIM-BCL-2 complex • ミトコンドリア外膜 • BIM-BCL-xl complex • cytoplasmic dynein complex • ミトコンドリア • 微小管 • 細胞内膜系 • extrinsic component of membrane • Bcl-2 family protein complex 生物学的プロセス • leukocyte homeostasis • regulation of apoptotic process • positive regulation of protein homooligomerization • 男性生殖腺発生 • positive regulation of cell death • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • B cell apoptotic process • 腎臓発生 • 胸腺発生 • lymphocyte homeostasis • positive regulation of apoptotic process by virus • myeloid cell homeostasis • post-embryonic animal organ morphogenesis • ear development • in utero embryonic development • B cell homeostasis • 脾臓発生 • thymocyte apoptotic process • post-embryonic development • response to endoplasmic reticulum stress • 乳房発達 • T cell homeostasis • odontogenesis of dentin-containing tooth • positive regulation of IRE1-mediated unfolded protein response • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • tube formation • 脳発生 • positive regulation of neuron apoptotic process • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • positive regulation of cell cycle • positive regulation of mitochondrial membrane permeability involved in apoptotic process • meiosis I • 精子形成 • intrinsic apoptotic signaling pathway in response to DNA damage • extrinsic apoptotic signaling pathway in absence of ligand • positive regulation of apoptotic process • positive regulation of fibroblast apoptotic process • 発生中の色素沈着 • positive regulation of release of cytochrome c from mitochondria • regulation of developmental pigmentation • cell-matrix adhesion • regulation of organ growth • activation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of intrinsic apoptotic signaling pathway • apoptotic process involved in embryonic digit morphogenesis • アポトーシス • protein insertion into mitochondrial membrane involved in apoptotic signaling pathway • positive regulation of autophagy in response to ER overload • 糖質コルチコイド刺激に対する細胞応答 • cellular response to estradiol stimulus • cellular response to amyloid-beta 出典:Amigo / QuickGO
オルソログ
種	ヒト	マウス
Entrez	10018	12125
Ensembl	ENSG00000153094	ENSMUSG00000027381
UniProt	O43521,E9PAM9	O54918
RefSeq (mRNA)	NM_001204106 NM_001204107 NM_001204108 NM_001204109 NM_001204110 NM_001204111 NM_001204112 NM_001204113 NM_006538 NM_138621 NM_138622 NM_138623 NM_138624 NM_138625 NM_138626 NM_138627 NM_207002 NM_207003	NM_001284410 NM_001291016 NM_009754 NM_207680 NM_207681
RefSeq (タンパク質)	NP_001191035 NP_001191036 NP_001191037 NP_001191038 NP_001191039 NP_001191040 NP_001191041 NP_001191042 NP_006529 NP_619527 NP_619528 NP_619529 NP_619530 NP_619531 NP_619532 NP_619533 NP_996885 NP_996886	NP_001271339 NP_001277945 NP_033884 NP_997563 NP_997564 NP_001392986 NP_001392987 NP_001392988 NP_001392989 NP_001392990
場所 (UCSC)	Chr 2: 111.12 – 111.17 Mb	Chr 2: 127.97 – 128 Mb
PubMed検索	[3]	[4]
ウィキデータ
閲覧/編集 ヒト 閲覧/編集 マウス

機能

BCL2L11はBcl-2ファミリーに属する。Bcl-2ファミリーのメンバーはヘテロ二量体またはホモ二量体を形成し、抗アポトーシスまたはアポトーシス促進性の調節因子として作用して広範囲の細胞活動と関係している。BCL2L11にはBH3ドメイン（Bcl-2 homology domain 3）が含まれており、他のBcl-2ファミリーのメンバーと相互作用してアポトーシスの活性化因子として作用する。BCL2L11遺伝子の発現は神経成長因子（NGF）やFKHR-L1（FOXO3a）によって誘導され、この遺伝子の神経細胞やリンパ球のアポトーシスにおける役割が示唆される。トランスジェニックマウスを用いた研究からは、胸腺における負の選択時のアポトーシスの開始因子として必須の機能を果たしていることが示唆されている^[7]。

調節

BCL2L11の発現と活性は、転写、翻訳、翻訳後の段階で調節されている。BCL2L11の協調的な発現と活性は免疫応答を形づくり、組織の完全性を保証している。がん細胞ではBCL2L11の発現を抑制する機構が形成されており、それによって腫瘍のプログレッションと転移が可能となっている^[8]。

相互作用

BCL2L11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^[5][6][9]
• BCL2L1（英語版）^{[5][6][9][10]}
• BCL2L2（英語版）^[5][6]
• DYNLL1（英語版）^[11][12]
• MCL1（英語版）^{[5][9][13][14]}

出典

1. GRCh38: Ensembl release 89: ENSG00000153094 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027381 - Ensembl, May 2017
3. Human PubMed Reference:
4. Mouse PubMed Reference:
5. “BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members”. Mol Endocrinol 12 (9): 1432–40. (November 1998). doi:10.1210/mend.12.9.0166. PMID 9731710.
6. “Bim: a novel member of the Bcl-2 family that promotes apoptosis”. EMBO J 17 (2): 384–95. (February 1998). doi:10.1093/emboj/17.2.384. PMC 1170389. PMID 9430630. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170389/.
7. “Entrez Gene: BCL2L11 BCL2-like 11 (apoptosis facilitator)”. 2024年11月16日閲覧。
8. “Regulation of Bim in Health and Disease”. Oncotarget 6 (27): 23058–134. (2015). doi:10.18632/oncotarget.5492. PMC 4695108. PMID 26405162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695108/.
9. “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.
10. “High-throughput methods to detect dimerization of Bcl-2 family proteins”. Anal. Biochem. 322 (2): 170–8. (November 2003). doi:10.1016/j.ab.2003.07.014. PMID 14596824.
11. “Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands”. Biochem. J. 377 (Pt 3): 597–605. (February 2004). doi:10.1042/BJ20031251. PMC 1223895. PMID 14561217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223895/.
12. “Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes”. Cancer Cell 5 (6): 575–85. (June 2004). doi:10.1016/j.ccr.2004.05.022. PMID 15193260.
13. “MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain”. J. Biol. Chem. 275 (33): 25255–61. (August 2000). doi:10.1074/jbc.M909826199. PMID 10837489.
14. Heckmeier, Philipp J.; Ruf, Jeannette; Buhrke, David; Janković, Brankica G.; Hamm, Peter (September 2022). “Signal Propagation Within the MCL-1/BIM Protein Complex”. Journal of Molecular Biology 434 (17): 167499. doi:10.1016/j.jmb.2022.167499. PMID 35189130.

関連文献

• “BID: a novel BH3 domain-only death agonist”. Genes Dev. 10 (22): 2859–69. (1996). doi:10.1101/gad.10.22.2859. PMID 8918887.
• “Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)”. Cell 87 (4): 619–28. (1997). doi:10.1016/S0092-8674(00)81382-3. PMID 8929531.
• “The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4”. EMBO J. 17 (4): 1029–39. (1998). doi:10.1093/emboj/17.4.1029. PMC 1170452. PMID 9463381. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1170452/.
• “The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex”. Mol. Cell 3 (3): 287–96. (1999). doi:10.1016/S1097-2765(00)80456-6. PMID 10198631.
• “A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region”. Cell Death Differ. 6 (4): 314–25. (1999). doi:10.1038/sj.cdd.4400493. PMID 10381623.
• “Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity”. Science 286 (5445): 1735–8. (1999). doi:10.1126/science.286.5445.1735. PMID 10576740.
• “Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1”. Curr. Biol. 10 (19): 1201–4. (2000). Bibcode: 2000CBio...10.1201D. doi:10.1016/S0960-9822(00)00728-4. PMID 11050388.
• “Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim”. Mamm. Genome 12 (2): 163–8. (2001). doi:10.1007/s003350010242. PMID 11210187.
• “Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis”. Neuron 29 (3): 615–28. (2001). doi:10.1016/S0896-6273(01)00238-0. PMID 11301022.
• “Assignment of BCL2L11 to human chromosome band 2p13 with somatic cell and radiation hybrids”. Cytogenet. Cell Genet. 92 (3–4): 353. (2001). doi:10.1159/000056930. PMID 11435715.
• “BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis”. Mol. Cell 8 (3): 705–11. (2001). doi:10.1016/S1097-2765(01)00320-3. PMID 11583631.
• “Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family”. FEBS Lett. 509 (1): 135–41. (2002). doi:10.1016/S0014-5793(01)03145-3. PMID 11734221.
• “BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes”. Nature 415 (6874): 922–6. (2002). doi:10.1038/415922a. PMID 11859372.
• “Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis”. Mol. Cell. Biol. 22 (11): 3577–89. (2002). doi:10.1128/MCB.22.11.3577-3589.2002. PMC 133811. PMID 11997495. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133811/.
• “Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim”. Cancer Res. 62 (10): 2976–81. (2002). PMID 12019181.
• “Direct addition of BimL to mitochondria does not lead to cytochrome c release”. FEBS Lett. 522 (1–3): 29–34. (2002). doi:10.1016/S0014-5793(02)02871-5. PMID 12095614.
• “Activation of mitochondrial voltage-dependent anion channel by apro-apoptotic BH3-only protein Bim”. Oncogene 21 (32): 4944–56. (2002). doi:10.1038/sj.onc.1205621. PMID 12118373.

関連項目

• Bcl-2