BAK1

کُشنده/آنتاگونیست همولوگ لنفوم ۲ لنفوسیت‌های بی (انگلیسی: Bcl-2 homologous antagonist killer‎) یک پروتئین است که در انسان توسط ژن «BAK1» واقع بر کروموزوم ۶ کُدگذاری می‌شود.[3][4]

BAK1
ساختارهای موجود PDB Ortholog search: PDBe RCSB List of PDB id codes 5AJK, 1BXL, 2IMS, 2IMT, 2JBY, 2JCN, 2LP8, 2M5B, 2XPX, 3I1H, 3QBR, 4D2L, 4U2U, 4U2V, 4UF1, 5FMK, 5FMI
معین‌کننده‌ها
نام‌های دیگر	BAK1, BAK, BAK-LIKE, BCL2L7, CDN1, BCL2 antagonist/killer 1
شناسه‌های بیرونی	OMIM: 600516 MGI: 1097161 HomoloGene: 917 GeneCards: BAK1
الگوی گسترش RNA More reference expression data
هستی‌شناسی ژن عملکرد ملکولی • ion channel binding • metal ion binding • GO:0001948 پیوند پروتئینی • identical protein binding • protein homodimerization activity • molecular function • heat shock protein binding • protein heterodimerization activity • chaperone binding • BH domain binding ترکیبات سلولی • integral component of membrane • سیتوزول • membrane • mitochondrial membrane • integral component of mitochondrial outer membrane • intracellular anatomical structure • شبکه آندوپلاسمی • میتوکندری • pore complex • mitochondrial outer membrane • BAK complex فرایند زیستی • mitochondrial fusion • leukocyte homeostasis • regulation of apoptotic process • positive regulation of endoplasmic reticulum unfolded protein response • establishment or maintenance of transmembrane electrochemical gradient • limb morphogenesis • positive regulation of calcium ion transport into cytosol • response to organic cyclic compound • B cell apoptotic process • regulation of protein heterodimerization activity • positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway • vagina development • homeostasis of number of cells • cellular response to UV • myeloid cell homeostasis • پیرش • post-embryonic camera-type eye morphogenesis • B cell homeostasis • thymocyte apoptotic process • endoplasmic reticulum calcium ion homeostasis • negative regulation of gene expression • regulation of cell cycle • regulation of mitochondrial membrane potential • positive regulation of IRE1-mediated unfolded protein response • blood vessel remodeling • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • brain development • response to fungus • regulation of mitochondrial membrane permeability • cellular response to mechanical stimulus • fibroblast apoptotic process • activation of cysteine-type endopeptidase activity • apoptotic process involved in blood vessel morphogenesis • activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c • animal organ regeneration • negative regulation of peptidyl-serine phosphorylation • positive regulation of proteolysis • positive regulation of release of cytochrome c from mitochondria • apoptotic signaling pathway • negative regulation of endoplasmic reticulum calcium ion concentration • cell population proliferation • response to ethanol • activation of cysteine-type endopeptidase activity involved in apoptotic process • response to gamma radiation • regulation of protein homodimerization activity • response to UV-C • response to hydrogen peroxide • response to drug • endocrine pancreas development • release of cytochrome c from mitochondria • B cell negative selection • negative regulation of cell population proliferation • response to mycotoxin • positive regulation of apoptotic process • intrinsic apoptotic signaling pathway in response to DNA damage • extrinsic apoptotic signaling pathway in absence of ligand • مرگ برنامه‌ریزی‌شده یاخته • cellular response to unfolded protein Sources:آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
گونه‌ها	انسان	موش
Entrez	578	12018
آنسامبل	ENSG00000030110	ENSMUSG00000057789
یونی‌پروت	Q16611	O08734
RefSeq (mRNA)	NM_001188، XM_011514779 XM_011514780، NM_001188، XM_011514779	NR_149749 NM_007523، NR_149749
RefSeq (پروتئین)	XP_011513081، XP_011513082 NP_001179، XP_011513081، XP_011513082	NP_031549
موقعیت (UCSC)	n/a	n/a
جستجوی PubMed	[1]	[2]
ویکی‌داده
مشاهده/ویرایش Human View/Edit Mouse

این پروتئین در میتوکندری واقع شده و در آغاز فرایند آپوپتوز نقش دارد.

اهمیت بالینی

تولید زیاد این پروتئین در بروز بیماری‌های تخریبی اعصاب و بیماری‌های خودایمنی و کاهش تولید آن در بروز سرطان نقش دارد.[5] به‌عنوان مثال، عدم تنظیم صحیح ژن «BAK1» در بروز سرطان لوله گوارش دخالت دارد و این موضوع نشان می‌دهد که این ژن در بیماری‌زایی برخی سرطان‌ها نقش دارد.[6][7]

این پروتئین همچنین در تزاید ویروس اچ‌آی‌وی مؤثر است[8] و داروهایی که بتوانند آنرا کنترل کنند، در درمان‌های آتی بیماری ایدز نویدبخش خواهند بود.[9]

تعامل شیمیایی

این پروتئین با مولکول پی۵۳[10][11] تعامل پروتئین-پروتئین دارد.

منابع

1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
2. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Chittenden T, Harrington EA, O'Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC (April 1995). "Induction of apoptosis by the Bcl-2 homologue Bak". Nature. 374 (6524): 733–6. Bibcode:1995Natur.374..733C. doi:10.1038/374733a0. PMID 7715730. S2CID 4315947.
4. Kiefer MC, Brauer MJ, Powers VC, Wu JJ, Umansky SR, Tomei LD, Barr PJ (April 1995). "Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak". Nature. 374 (6524): 736–9. Bibcode:1995Natur.374..736K. doi:10.1038/374736a0. PMID 7715731. S2CID 4087773.
5. Cartron PF, Petit E, Bellot G, Oliver L, Vallette FM (September 2014). "Metaxins 1 and 2, two proteins of the mitochondrial protein sorting and assembly machinery, are essential for Bak activation during TNF alpha triggered apoptosis". Cellular Signalling. 26 (9): 1928–34. doi:10.1016/j.cellsig.2014.04.021. PMID 24794530.
6. Tong QS, Zheng LD, Wang L, Liu J, Qian W (July 2004). "BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells". BMC Cancer. 4: 33. doi:10.1186/1471-2407-4-33. PMC 481072. PMID 15248898.
7. Duckworth CA, Pritchard DM (March 2009). "Suppression of apoptosis, crypt hyperplasia, and altered differentiation in the colonic epithelia of bak-null mice". Gastroenterology. 136 (3): 943–52. doi:10.1053/j.gastro.2008.11.036. PMID 19185578.
8. Sainski AM, Dai H, Natesampillai S, Pang YP, Bren GD, Cummins NW, Correia C, Meng XW, Tarara JE, Ramirez-Alvarado M, Katzmann DJ, Ochsenbauer C, Kappes JC, Kaufmann SH, Badley AD (September 2014). "Casp8p41 generated by HIV protease kills CD4 T cells through direct Bak activation". The Journal of Cell Biology. 206 (7): 867–76. doi:10.1083/jcb.201405051. PMC 4178959. PMID 25246614.
9. Westphal D, Kluck RM, Dewson G (February 2014). "Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis". Cell Death and Differentiation. 21 (2): 196–205. doi:10.1038/cdd.2013.139. PMC 3890949. PMID 24162660.
10. "Entrez Gene: BAK1 BCL2-antagonist/killer 1".
11. Perfettini JL, Kroemer RT, Kroemer G (May 2004). "Fatal liaisons of p53 with Bax and Bak". Nature Cell Biology. 6 (5): 386–8. doi:10.1038/ncb0504-386. PMID 15122264. S2CID 21913599.

• مشارکت‌کنندگان ویکی‌پدیا. «Bcl-2 homologous antagonist killer». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۲۴ اکتبر ۲۰۲۰.

برای مطالعهٔ بیشتر

• Buytaert E, Callewaert G, Vandenheede JR, Agostinis P (2007). "Deficiency in apoptotic effectors Bax and Bak reveals an autophagic cell death pathway initiated by photodamage to the endoplasmic reticulum". Autophagy. 2 (3): 238–40. doi:10.4161/auto.2730. PMID 16874066.
• Farrow SN, White JH, Martinou I, Raven T, Pun KT, Grinham CJ, Martinou JC, Brown R (April 1995). "Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K". Nature. 374 (6524): 731–3. Bibcode:1995Natur.374..731F. doi:10.1038/374731a0. PMID 7715729. S2CID 4338100.
• Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ (November 1995). "A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions". The EMBO Journal. 14 (22): 5589–96. doi:10.1002/j.1460-2075.1995.tb00246.x. PMC 394673. PMID 8521816.
• Sattler M, Liang H, Nettesheim D, Meadows RP, Harlan JE, Eberstadt M, Yoon HS, Shuker SB, Chang BS, Minn AJ, Thompson CB, Fesik SW (February 1997). "Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis". Science. 275 (5302): 983–6. doi:10.1126/science.275.5302.983. PMID 9020082. S2CID 22667419.
• Diaz JL, Oltersdorf T, Horne W, McConnell M, Wilson G, Weeks S, Garcia T, Fritz LC (April 1997). "A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members". The Journal of Biological Chemistry. 272 (17): 11350–5. doi:10.1074/jbc.272.17.11350. PMID 9111042.
• Huang DC, Adams JM, Cory S (February 1998). "The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4". The EMBO Journal. 17 (4): 1029–39. doi:10.1093/emboj/17.4.1029. PMC 1170452. PMID 9463381.
• Herberg JA, Phillips S, Beck S, Jones T, Sheer D, Wu JJ, Prochazka V, Barr PJ, Kiefer MC, Trowsdale J (April 1998). "Genomic structure and domain organisation of the human Bak gene". Gene. 211 (1): 87–94. doi:10.1016/S0378-1119(98)00101-2. PMID 9573342.
• Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (December 1998). "Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria". Proceedings of the National Academy of Sciences of the United States of America. 95 (25): 14681–6. Bibcode:1998PNAS...9514681N. doi:10.1073/pnas.95.25.14681. PMC 24509. PMID 9843949.
• Song Q, Kuang Y, Dixit VM, Vincenz C (January 1999). "Boo, a novel negative regulator of cell death, interacts with Apaf-1". The EMBO Journal. 18 (1): 167–78. doi:10.1093/emboj/18.1.167. PMC 1171112. PMID 9878060.
• Griffiths GJ, Dubrez L, Morgan CP, Jones NA, Whitehouse J, Corfe BM, Dive C, Hickman JA (March 1999). "Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis". The Journal of Cell Biology. 144 (5): 903–14. doi:10.1083/jcb.144.5.903. PMC 2148192. PMID 10085290.
• Shimizu S, Narita M, Tsujimoto Y (June 1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature. 399 (6735): 483–7. Bibcode:1999Natur.399..483S. doi:10.1038/20959. PMID 10365962. S2CID 4423304.
• Ohi N, Tokunaga A, Tsunoda H, Nakano K, Haraguchi K, Oda K, Motoyama N, Nakajima T (April 1999). "A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region". Cell Death and Differentiation. 6 (4): 314–25. doi:10.1038/sj.cdd.4400493. PMID 10381623.
• Holmgreen SP, Huang DC, Adams JM, Cory S (June 1999). "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members". Cell Death and Differentiation. 6 (6): 525–32. doi:10.1038/sj.cdd.4400519. PMID 10381646.
• Leo CP, Hsu SY, Chun SY, Bae HW, Hsueh AJ (December 1999). "Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary". Endocrinology. 140 (12): 5469–77. doi:10.1210/en.140.12.5469. PMID 10579309.
• Shimizu S, Tsujimoto Y (January 2000). "Proapoptotic BH3-only Bcl-2 family members induce cytochrome c release, but not mitochondrial membrane potential loss, and do not directly modulate voltage-dependent anion channel activity". Proceedings of the National Academy of Sciences of the United States of America. 97 (2): 577–82. Bibcode:2000PNAS...97..577S. doi:10.1073/pnas.97.2.577. PMC 15372. PMID 10639121.
• Bae J, Leo CP, Hsu SY, Hsueh AJ (August 2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain". The Journal of Biological Chemistry. 275 (33): 25255–61. doi:10.1074/jbc.M909826199. PMID 10837489.
• Wei MC, Lindsten T, Mootha VK, Weiler S, Gross A, Ashiya M, Thompson CB, Korsmeyer SJ (August 2000). "tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c". Genes & Development. 14 (16): 2060–71. PMC 316859. PMID 10950869.
• Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan J (February 2001). "Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL". Nature Cell Biology. 3 (2): 173–82. doi:10.1038/35055085. PMID 11175750. S2CID 32934759.
• Duckworth CA, Pritchard DM (March 2009). "Suppression of apoptosis, crypt hyperplasia, and altered differentiation in the colonic epithelia of bak-null mice". Gastroenterology. 136 (3): 943–52. doi:10.1053/j.gastro.2008.11.036. PMID 19185578.

پیوند به بیرون

• مکان ژنوم BAK1 انسانی و صفحهٔ جزئیات ژنی BAK1 در سامانه جستجوی بانک ژنی دانشگاه کالیفرنیا، سانتا کروز.