胱天蛋白酶2

胱天蛋白酶2
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1PYO、2P2C、3R5J、3R6G、3R6L、3R7B、3R7N、3R7S、3RJM
识别号
别名	CASP2；, CASP-2, ICH1, NEDD-2, NEDD2, PPP1R57, caspase 2
外部ID	OMIM：600639 MGI：97295 HomoloGene：7254 GeneCards：CASP2
为以下药物的标靶
	emricasan
基因位置（人类）
染色体	7号染色体
终止	143,307,696 bp
基因位置（小鼠）
染色体	小鼠6号染色体
终止	42,259,442 bp
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本体
分子功能	• 半胱氨酸型肽酶活性; • protein domain specific binding; • 肽酶活性; • 血浆蛋白结合; • 酶结合; • 水解酶活性; • 相同蛋白质结合; • cysteine-type endopeptidase activity involved in apoptotic process; • cysteine-type endopeptidase activity; • cysteine-type endopeptidase activity involved in execution phase of apoptosis;
细胞组分	• 细胞质; • 细胞质基质; • 膜; • 线粒体; • 细胞核;
生物学过程	• DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; • execution phase of apoptosis; • protein processing; • 老化; • positive regulation of apoptotic signaling pathway; • 黄体溶解; • cellular response to mechanical stimulus; • positive regulation of neuron apoptotic process; • brain development; • intrinsic apoptotic signaling pathway in response to DNA damage; • extrinsic apoptotic signaling pathway in absence of ligand; • positive regulation of apoptotic process; • ectopic germ cell programmed cell death; • apoptotic signaling pathway; • neural retina development; • 细胞凋亡; • regulation of apoptotic process; • 蛋白酶解; • negative regulation of apoptotic process;
	Sources:Amigo / QuickGO
直系同源
	835
	12366
	ENSG00000106144
	ENSMUSG00000029863
	P42575
	P29594
	NM_032983; NM_001224; NM_032982; NM_032984
	NM_007610
	NP_001215; NP_116764; NP_116765
	NP_031636
	维基数据
查看/编辑人类	查看/编辑小鼠

胱天蛋白酶2是一种在人类中由CASP2基因编码的酶。^[6]几乎所有可获得完整基因组数据的哺乳动物中都已鉴定出CASP2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。

功能

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。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上进行蛋白酶解加工，产生两个亚基，分别为大的和小的，它们二聚化形成活性酶。该蛋白质的蛋白酶解裂解是由多种细胞凋亡刺激诱导的。^[8]

胱天蛋白酶2通过蛋白酶解裂解其他蛋白质。它属于称为胱天蛋白酶的半胱氨酸蛋白酶家族，仅在天冬氨酸残基后的氨基酸处切割蛋白质。在该家族中，胱天蛋白酶2属于Ich-1亚家族。它是不同物种动物中最保守的胱天蛋白酶之一。胱天蛋白酶2与起始胱天蛋白酶具有相似的氨基酸序列，包括胱天蛋白酶1、胱天蛋白酶4、胱天蛋白酶5和胱天蛋白酶9。它作为酶原产生，包含一个与胱天蛋白酶9相似的长前结构域，并包含称为CARD结构域的蛋白质相互作用结构域。胱天蛋白酶原2包含两个亚基：p19和p12。

它已被证明与使用其CARD结构域参与细胞凋亡的多种蛋白质相关，包括具有死亡结构域的RIP相关Ich-1/Ced-3同源蛋白（RAIDD）、具有胱天蛋白酶募集结构域（ARC）的细胞凋亡抑制蛋白，以及死亡效应丝形成 Ced-4 样凋亡蛋白（DEFCAP）。^[9]胱天蛋白酶2与RAIDD和带有死亡结构域（PIDD或LRDD）的p53诱导蛋白一起形成所谓的PIDDosome，^[10]它可以作为蛋白酶的激活平台，尽管它也可能是在没有PIDD的情况下激活。^[11]总体而言，胱天蛋白酶2似乎是一种用途广泛的胱天蛋白酶，除了诱导细胞死亡外还具有多种功能。^[12]^[13]

相互作用

胱天蛋白酶2已被证明可以与以下物质相互作用：

BH3相互作用域死亡激动剂（英语：BH3 interacting-domain death agonist）^[14]^[15]
CRADD^[10]^[16]^[17]
胱天蛋白酶8^[14]^[18]

参见

蛋白酶解图谱（英语：The Proteolysis Map）
胱天蛋白酶

参考资料

^ 對Caspase 2起作用的藥物；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000106144 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000029863 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Kumar S, White DL, Takai S, Turczynowicz S, Juttner CA, Hughes TP. Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms. Hum. Genet. June 1995, 95 (6): 641–4. PMID 7789948. S2CID 22813779. doi:10.1007/bf00209480.
^ OrthoMaM phylogenetic marker: CASP2 coding sequence. [20 December 2009]. （原始内容存档于24 September 2015）.
^ Entrez Gene: CASP2.
^ Zhivotovsky B, Orrenius S. Caspase-2 function in response to DNA damage. Biochem. Biophys. Res. Commun. 2005, 331 (3): 859–67. PMID 15865942. doi:10.1016/j.bbrc.2005.03.191  .
^ ^10.0 ^10.1 Tinel A, Tschopp J. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science. May 2004, 304 (5672): 843–6. Bibcode:2004Sci...304..843T. PMID 15073321. S2CID 6583298. doi:10.1126/science.1095432.
^ Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A. Caspase-2 activation in the absence of PIDDosome formation. J. Cell Biol. April 2009, 185 (2): 291–303 [2024-01-20]. PMC 2700374  . PMID 19364921. doi:10.1083/jcb.200811105. （原始内容存档于2023-03-28）.
^ Krumschnabel G, Manzl C, Villunger A. Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase. Oncogene. September 2009, 28 (35): 3093–6. PMC 3272399  . PMID 19581929. doi:10.1038/onc.2009.173.
^ Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A. The enigma of caspase-2: the laymen's view. Cell Death Differ. February 2009, 16 (2): 195–207. PMC 3272397  . PMID 19023332. doi:10.1038/cdd.2008.170.
^ ^14.0 ^14.1 Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem. April 2002, 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200  .
^ Paroni G, Henderson C, Schneider C, Brancolini C. Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3. J. Biol. Chem. June 2001, 276 (24): 21907–15. PMID 11399776. doi:10.1074/jbc.M011565200  .
^ Droin N, Beauchemin M, Solary E, Bertrand R. Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade. Cancer Res. December 2000, 60 (24): 7039–47. PMID 11156409.
^ Duan H, Dixit VM. RAIDD is a new 'death' adaptor molecule (PDF). Nature. January 1997, 385 (6611): 86–9. Bibcode:1997Natur.385...86D. PMID 8985253. S2CID 4317538. doi:10.1038/385086a0. hdl:2027.42/62739  .
^ 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. December 1996, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159  . PMID 8962078. doi:10.1073/pnas.93.25.14486  .

外部链接

The MEROPS online database for peptidases and their inhibitors: C14.006^{[失效链接]}
PDB中UniProt可用的所有结构信息之概述：P42575 (Human Caspase-2) 在PDBe-KB（英语：PDBe-KB）。

胱天蛋白酶2引用了美国国家医学图书馆提供的数据，这些数据属于公共领域。

[1] 對Caspase 2起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000106144 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000029863 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7789948-6] Kumar S, White DL, Takai S, Turczynowicz S, Juttner CA, Hughes TP. Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms. Hum. Genet. June 1995, 95 (6): 641–4. PMID 7789948. S2CID 22813779. doi:10.1007/bf00209480.

[OrthoMaM-7] OrthoMaM phylogenetic marker: CASP2 coding sequence. [20 December 2009]. （原始内容存档于24 September 2015）.

[entrez-8] Entrez Gene: CASP2.

[9] Zhivotovsky B, Orrenius S. Caspase-2 function in response to DNA damage. Biochem. Biophys. Res. Commun. 2005, 331 (3): 859–67. PMID 15865942. doi:10.1016/j.bbrc.2005.03.191  .

[pmid15073321-10] 10.0 ^10.1 Tinel A, Tschopp J. The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science. May 2004, 304 (5672): 843–6. Bibcode:2004Sci...304..843T. PMID 15073321. S2CID 6583298. doi:10.1126/science.1095432.

[pmid19364921-11] Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A. Caspase-2 activation in the absence of PIDDosome formation. J. Cell Biol. April 2009, 185 (2): 291–303 [2024-01-20]. PMC 2700374  . PMID 19364921. doi:10.1083/jcb.200811105. （原始内容存档于2023-03-28）.

[pmid19581929-12] Krumschnabel G, Manzl C, Villunger A. Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase. Oncogene. September 2009, 28 (35): 3093–6. PMC 3272399  . PMID 19581929. doi:10.1038/onc.2009.173.

[pmid19023332-13] Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A. The enigma of caspase-2: the laymen's view. Cell Death Differ. February 2009, 16 (2): 195–207. PMC 3272397  . PMID 19023332. doi:10.1038/cdd.2008.170.

[pmid11832478-14] 14.0 ^14.1 Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem. April 2002, 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200  .

[pmid11399776-15] Paroni G, Henderson C, Schneider C, Brancolini C. Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3. J. Biol. Chem. June 2001, 276 (24): 21907–15. PMID 11399776. doi:10.1074/jbc.M011565200  .

[pmid11156409-16] Droin N, Beauchemin M, Solary E, Bertrand R. Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade. Cancer Res. December 2000, 60 (24): 7039–47. PMID 11156409.

[pmid8985253-17] Duan H, Dixit VM. RAIDD is a new 'death' adaptor molecule (PDF). Nature. January 1997, 385 (6611): 86–9. Bibcode:1997Natur.385...86D. PMID 8985253. S2CID 4317538. doi:10.1038/385086a0. hdl:2027.42/62739  .

[pmid8962078-18] 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. December 1996, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159  . PMID 8962078. doi:10.1073/pnas.93.25.14486  .

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