胱天蛋白酶6

胱天蛋白酶6（英语：Caspase 6）是人类中由CASP6基因编码的一种酶。^[5][6]许多可获得完整基因组数据的哺乳动物中都已鉴定出CASP6直向同源物。^[7]鸟类、蜥蜴、滑体动物和真骨类中也存在独特的直系同源物。胱天蛋白酶6在亨廷顿舞蹈症和阿尔茨海默病的细胞凋亡、^[8]早期免疫反应^[9][10]和神经变性中具有重要功能。^[11]

胱天蛋白酶6
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 2WDP、​3K7E、​3NKF、​3NR2、​3OD5、​3P45、​3P4U、​3QNW、​3S70、​3S8E、​3V6L、​3V6M、​4EJF、​4FXO、​4HVA、​4IYR、​4N5D、​4N6G、​4N7J、​4N7M、​4NBK、​4NBL、​4NBN
识别号
别名	CASP6；, MCH2, Caspase 6, CSP-6
外部ID	OMIM：601532 MGI：1312921 HomoloGene：37455 GeneCards：CASP6
基因位置（人类） 染色体 4号染色体[1] 基因座 4q25 起始 109,688,622 bp[1] 终止 109,703,583 bp[1]
基因位置（小鼠） 染色体 小鼠3号染色体[2] 基因座 3|3 G3 起始 129,695,074 bp[2] 终止 129,707,752 bp[2]
RNA表达模式
查阅更多表达数据
基因本体 分子功能 • 肽酶活性 • cysteine-type endopeptidase activity • 半胱氨酸型肽酶活性 • endopeptidase activity • 血浆蛋白结合 • 水解酶活性 • 相同蛋白质结合 • cysteine-type endopeptidase activity involved in execution phase of apoptosis • cysteine-type endopeptidase activity involved in apoptotic process 细胞组分 • 细胞质基质 • 核质 • 细胞质 生物学过程 • epithelial cell differentiation • 蛋白酶解 • 细胞凋亡 • regulation of apoptotic process • execution phase of apoptosis • cellular response to staurosporine Sources:Amigo / QuickGO
直系同源
物种	人类	小鼠
Entrez	839	12368
Ensembl	ENSG00000138794	ENSMUSG00000027997
UniProt	P55212	O08738
mRNA​序列	NM_001226 ​NM_032992	NM_009811
蛋白序列	NP_001217 ​NP_116787	NP_033941
基因位置​（UCSC）	Chr 4: 109.69 – 109.7 Mb	Chr 3: 129.7 – 129.71 Mb
PubMed​查找	[3]	[4]
维基数据
查看/编辑人类 查看/编辑小鼠

作用

该基因编码的蛋白质是胱天蛋白酶家族的成员。胱天蛋白酶的连续激活在细胞凋亡的执行阶段发挥着核心作用。^[8]胱天蛋白酶以无活性的酶原形式存在，在保守的天冬氨酸残基处经历蛋白水解加工，产生一大一小两个亚基，然后二聚化形成活性酶。该蛋白由胱天蛋白酶7、8和10加工，被认为是胱天蛋白酶激活级联中的下游酶。胱天蛋白酶6也可以在没有胱天蛋白酶家族其他成员的情况下进行自我加工。^[12]该基因的选择性剪接产生了编码不同亚型的两个转录变体。^[13]

胱天蛋白酶6通过去抑制在早期免疫反应中发挥作用。它降低免疫抑制剂细胞因子白细胞介素10^[9]的表达，并裂解巨噬细胞上表达的IRAK-M来抑制巨噬细胞。^[10]

对于神经变性，胱天蛋白酶6可以裂解亨廷顿舞蹈症中的亨廷顿蛋白（HTT）和阿尔茨海默病中的前类淀粉蛋白质（APP）。这两种情况都会导致片段的蛋白质聚集。^[11]

相互作用

胱天蛋白酶6已被证明与胱天蛋白酶8发生相互作用。^[14][15][16]

参见

• 蛋白酶解图谱
• 胱天蛋白酶

参考文献

1. GRCh38: Ensembl release 89: ENSG00000138794 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027997 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA. Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. Biochem Biophys Res Commun. Oct 1996, 225 (3): 983–9. PMID 8780721. doi:10.1006/bbrc.1996.1282.
6. Fernandes-Alnemri T, Litwack G, Alnemri ES. Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. Cancer Res. Aug 1995, 55 (13): 2737–42. PMID 7796396.
7. OrthoMaM phylogenetic marker: CASP6 coding sequence. [2009-12-20]. （原始内容存档于2016-03-03）.
8. Cohen, Gerald M. Caspases: the executioners of apoptosis. Biochemical Journal. 1997-08-15, 326 (1): 1–16. ISSN 0264-6021. PMC 1218630 . PMID 9337844. doi:10.1042/bj3260001 （英语）.
9. Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin. Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines. PLOS ONE. 2017-07-07, 12 (7): e0180203. Bibcode:2017PLoSO..1280203B. ISSN 1932-6203. PMC 5501493 . PMID 28686630. doi:10.1371/journal.pone.0180203 .
10. Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M. The Journal of Immunology. 2011-01-01, 186 (1): 403–410. ISSN 0022-1767. PMC 3151149 . PMID 21098228. doi:10.4049/jimmunol.1001906 （英语）.
11. Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. Caspase-6 and neurodegeneration. Trends in Neurosciences. 2011-12-01, 34 (12): 646–656 [2024-02-02]. ISSN 0166-2236. PMID 22018804. S2CID 1603684. doi:10.1016/j.tins.2011.09.001. （原始内容存档于2013-10-16） （英语）.
12. Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD. Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation. EMBO Rep. Nov 2010, 11 (11): 841–7. PMC 2966951 . PMID 20890311. doi:10.1038/embor.2010.141.
13. Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase.
14. Cowling V, Downward J. Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain. Cell Death Differ. Oct 2002, 9 (10): 1046–56. PMID 12232792. doi:10.1038/sj.cdd.4401065 .
15. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem. Apr 2002, 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200 .
16. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES. Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc. Natl. Acad. Sci. U.S.A. Dec 1996, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159 . PMID 8962078. doi:10.1073/pnas.93.25.14486 .

拓展阅读

• Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J. Biol. Chem. 1995, 269 (49): 30761–4. PMID 7983002. doi:10.1016/S0021-9258(18)47344-9 .
• Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC. Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis. Proc. Natl. Acad. Sci. U.S.A. 1996, 93 (16): 8395–400. Bibcode:1996PNAS...93.8395T. PMC 38682 . PMID 8710882. doi:10.1073/pnas.93.16.8395 .
• Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM. Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3. Genomics. 1997, 36 (2): 362–5. PMID 8812467. doi:10.1006/geno.1996.0476.
• Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES. The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32. J. Biol. Chem. 1996, 271 (43): 27099–106. PMID 8900201. doi:10.1074/jbc.271.43.27099 .
• Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES. Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc. Natl. Acad. Sci. U.S.A. 1997, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159 . PMID 8962078. doi:10.1073/pnas.93.25.14486 .
• Rao L, Perez D, White E. Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell Biol. 1997, 135 (6 Pt 1): 1441–55. PMC 2133948 . PMID 8978814. doi:10.1083/jcb.135.6.1441.
• Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science. 1998, 277 (5324): 373–6. CiteSeerX 10.1.1.1025.8052 . PMID 9219695. doi:10.1126/science.277.5324.373.
• Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. J. Biol. Chem. 1997, 272 (30): 18542–5. PMID 9228018. doi:10.1074/jbc.272.30.18542 .
• Caulín C, Salvesen GS, Oshima RG. Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis. J. Cell Biol. 1997, 138 (6): 1379–94. PMC 2132555 . PMID 9298992. doi:10.1083/jcb.138.6.1379.
• Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M. Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis. J. Exp. Med. 1998, 187 (4): 587–600. PMC 2212161 . PMID 9463409. doi:10.1084/jem.187.4.587.
• Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S. Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis. J. Biol. Chem. 1998, 273 (22): 13524–30. PMID 9593687. doi:10.1074/jbc.273.22.13524 .
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• Samejima K, Svingen PA, Basi GS, Kottke T, Mesner PW, Stewart L, Durrieu F, Poirier GG, Alnemri ES, Champoux JJ, Kaufmann SH, Earnshaw WC. Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis. J. Biol. Chem. 1999, 274 (7): 4335–40. PMID 9933635. doi:10.1074/jbc.274.7.4335 .
• Walter J, Schindzielorz A, Grünberg J, Haass C. Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis. Proc. Natl. Acad. Sci. U.S.A. 1999, 96 (4): 1391–6. Bibcode:1999PNAS...96.1391W. PMC 15473 . PMID 9990034. doi:10.1073/pnas.96.4.1391 .
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外部链接

• 肽酶及其抑制剂的MEROPS在线数据库：C14.005 （页面存档备份，存于互联网档案馆）
• PDB中UniProt可用的所有结构信息之概述：P55212 (Human Caspase-6) 在PDBe-KB（英语：PDBe-KB）。