组织蛋白酶Z

组织蛋白酶Z
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1DEU、1EF7
識別號
别名	CTSZ；, CTSX, cathepsin Z
外部ID	OMIM：603169 MGI：1891190 HomoloGene：1022 GeneCards：CTSZ
為以下藥物的標靶
	odanacatib[1]
基因位置（人类）
染色体	20號染色體[2]
终止	59,008,238 bp[2]
基因位置（小鼠）
染色体	小鼠2号染色体[3]
终止	174,280,832 bp[3]
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• 血浆蛋白结合; • 肽酶活性; • 水解酶活性; • cysteine-type endopeptidase activity; • 半胱氨酸型肽酶活性; • carboxypeptidase activity;
細胞組分	• endoplasmic reticulum lumen; • COPII-coated ER to Golgi transport vesicle; • 細胞內膜結合細胞器; • 内质网; • 细胞膜; • endoplasmic reticulum-Golgi intermediate compartment membrane; • 外排體; • Golgi membrane; • 細胞外區域; • specific granule lumen; • ficolin-1-rich granule lumen; • 細胞外空間; • 溶酶体; • cell surface; • 生长锥; • cytoplasmic vesicle; • cell cortex region; • collagen-containing extracellular matrix;
生物學過程	• proteolysis involved in cellular protein catabolic process; • COPII vesicle coating; • endoplasmic reticulum to Golgi vesicle-mediated transport; • epithelial tube branching involved in lung morphogenesis; • angiotensin maturation; • neutrophil degranulation; • 蛋白酶解; • negative regulation of plasminogen activation; • negative regulation of neuron projection development; • negative regulation of protein binding; • positive regulation of neuron apoptotic process; • regulation of neuron death; • positive regulation of neural precursor cell proliferation;
	Sources:Amigo / QuickGO
直系同源
	1522
	64138
	ENSG00000101160
	ENSMUSG00000016256
	Q9UBR2
	Q9WUU7
	NM_001336
	NM_022325
	NP_001327
	NP_071720
	維基數據

组织蛋白酶Z，也称为组织蛋白酶X或组织蛋白酶P，是一种在人体中由CTSZ基因编码的蛋白质。[6][7]它是半胱氨酸蛋白酶的半胱氨酸组织蛋白酶家族的成员，该家族有11个成员。[8]作为11种组织蛋白酶之一，组织蛋白酶Z具有与众不同的特征。据报道，组织蛋白酶Z与恶性肿瘤和炎症有关。

结构

基因

CTSZ基因位于20号染色体的20q13.32，由6个外显子组成。已发现该基因的至少两种转录变体，但仅确定了其中一种的全长性质。[7]

蛋白质

组织蛋白酶Z的特点是在假定的氧离子孔的谷氨酰胺和活性位点半胱氨酸之间的高度保守区域中插入了不寻常且独特的3个氨基酸。组织蛋白酶Z的前区与其他组织蛋白酶家族序列没有显着相似性。[9]它仅包含41个氨基酸残基，没有在其他半胱氨酸蛋白酶中发现的ERFNIN或GNFD的保守基序。此外，前区序列不含赖氨酸残基。

功能

该基因编码的蛋白质是一种溶酶体半胱氨酸蛋白酶，是肽酶C1家族的成员。它表现出羧单肽酶和羧二肽酶活性。迄今为止，已鉴定出11种人类半胱氨酸蛋白酶，包括组织蛋白酶B、组织蛋白酶C、组织蛋白酶F、组织蛋白酶H、组织蛋白酶K、组织蛋白酶L1、组织蛋白酶L2或V、组织蛋白酶O、组织蛋白酶S、组织蛋白酶Z和组织蛋白酶W。这些半胱氨酸蛋白酶属于木瓜蛋白酶家族，是溶酶体蛋白酶解系统的主要成分。除了在蛋白质降解和转换中发挥关键作用外，这些蛋白酶似乎在许多正常和病理条件下发挥细胞外作用。人类组织蛋白酶Z包含与其他人类半胱氨酸蛋白酶不同的特征。[10]它是一种具有严格羧肽酶活性的外肽酶，而大多数其他组织蛋白酶是内肽酶。[8]组织蛋白酶Z在酶的前肽内具有暴露的整合素结合Arg-Gly-Asp基序，已显示组织蛋白酶Z在正常体内平衡、免疫过程和癌症期间通过该基序与几种整合素相互作用。[11][12][13][14]它还显示与细胞表面的硫酸肝素蛋白聚糖结合，表明可能在细胞黏附和吞噬作用中发挥作用。[15]

临床意义

该基因在癌细胞系和原发性肿瘤中普遍表达，并且与该家族的其他成员一样，可能参与肿瘤发生。例如，组织蛋白酶Z通过非催化机制促进侵袭和迁移，这表明多种细胞侵袭模式可能与恶性肿瘤有关。[14]组织蛋白酶Z在炎症性胃病中也具有保护作用，但不是蛋白酶解作用。[16]在另一项研究中显示，组织蛋白酶Z可能是导致多巴胺神经元死亡的原因，因此参与了致病级联事件。[17]组织蛋白酶Z中的单核苷酸多态性被发现与结核病易感性有关，表明涉及该蛋白质的途径可以产生结核病的新疗法。[18]

相互作用

组织蛋白酶Z已被证明与以下蛋白质相互作用：CEP55, FBXO6, KIFC1, KRT40, KRTAP5-9, KRTAP5-9, LYPLAL1, MID2, MSN, MTUS2, NOTCH2NL, PLK2, PLSCR1, SGOL2, and SPRED2.[19]

还发现组织蛋白酶Z与以下物质相互作用：

参考文献

.
GRCh38: Ensembl release 89: ENSG00000101160 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000016256 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
Santamaría I, Velasco G, Pendás AM, Fueyo A, López-Otín C. . The Journal of Biological Chemistry. July 1998, 273 (27): 16816–23. PMID 9642240. doi:10.1074/jbc.273.27.16816 .
. [2022-11-01]. （原始内容存档于2010-03-08）.
Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, Turk D. . Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. January 2012, 1824 (1): 68–88. PMC 7105208 . PMID 22024571. doi:10.1016/j.bbapap.2011.10.002 .
Nägler DK, Zhang R, Tam W, Sulea T, Purisima EO, Ménard R. . Biochemistry. September 1999, 38 (39): 12648–54. PMID 10504234. doi:10.1021/bi991371z.
Nägler DK, Ménard R. . FEBS Letters. August 1998, 434 (1–2): 135–9. PMID 9738465. S2CID 22899822. doi:10.1016/s0014-5793(98)00964-8 .
Lechner AM, Assfalg-Machleidt I, Zahler S, Stoeckelhuber M, Machleidt W, Jochum M, Nägler DK. . The Journal of Biological Chemistry. December 2006, 281 (51): 39588–97. PMID 17065156. doi:10.1074/jbc.M513439200 .
Kos J, Jevnikar Z, Obermajer N. . Cell Adhesion & Migration. April–June 2009, 3 (2): 164–6. PMC 2679876 . PMID 19262176. doi:10.4161/cam.3.2.7403.
Obermajer N, Svajger U, Bogyo M, Jeras M, Kos J. . Journal of Leukocyte Biology. November 2008, 84 (5): 1306–15. PMC 3252843 . PMID 18701767. doi:10.1189/jlb.0508285.
Akkari L, Gocheva V, Kester JC, Hunter KE, Quick ML, Sevenich L, Wang HW, Peters C, Tang LH, Klimstra DS, Reinheckel T, Joyce JA. . Genes & Development. October 2014, 28 (19): 2134–50. PMC 4180975 . PMID 25274726. doi:10.1101/gad.249599.114.
Teller A, Jechorek D, Hartig R, Adolf D, Reißig K, Roessner A, Franke S. . Pathology, Research and Practice. January 2015, 211 (1): 62–70. PMID 25433997. doi:10.1016/j.prp.2014.09.005.
Krueger S, Bernhardt A, Kalinski T, Baldensperger M, Zeh M, Teller A, Adolf D, Reinheckel T, Roessner A, Kuester D. . PLOS ONE. 2013, 8 (7): e70242. PMC 3728094 . PMID 23936173. doi:10.1371/journal.pone.0070242 .
Pišlar AH, Zidar N, Kikelj D, Kos J. . Neuropharmacology. July 2014, 82: 121–31. PMID 23958447. S2CID 22499368. doi:10.1016/j.neuropharm.2013.07.040.
Adams LA, Möller M, Nebel A, Schreiber S, van der Merwe L, van Helden PD, Hoal EG. . European Journal of Human Genetics. June 2011, 19 (6): 676–81. PMC 3110050 . PMID 21368909. doi:10.1038/ejhg.2011.1.
. BioGRID. [6 August 2016]. （原始内容存档于2022-11-01）.
Hafner A, Glavan G, Obermajer N, Živin M, Schliebs R, Kos J. . Aging Cell. August 2013, 12 (4): 604–14. PMID 23621429. S2CID 23835547. doi:10.1111/acel.12093 .

阅读

Nägler DK, Ménard R. . FEBS Letters. August 1998, 434 (1–2): 135–9. PMID 9738465. S2CID 22899822. doi:10.1016/S0014-5793(98)00964-8 .
Pungercar J, Ivanovski G. . Pflügers Archiv. 2000, 439 (3 Suppl): R116–8. PMID 10653162. S2CID 22775842. doi:10.1007/s004240000112.
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Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A. . Genome Research. October 2004, 14 (10B): 2136–44. PMC 528930 . PMID 15489336. doi:10.1101/gr.2576704.
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Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S. . Nucleic Acids Research. January 2006, 34 (Database issue): D415–8. PMC 1347501 . PMID 16381901. doi:10.1093/nar/gkj139.
Lechner AM, Assfalg-Machleidt I, Zahler S, Stoeckelhuber M, Machleidt W, Jochum M, Nägler DK. . The Journal of Biological Chemistry. December 2006, 281 (51): 39588–97. PMID 17065156. doi:10.1074/jbc.M513439200 .

外部链接

The MEROPS online database for peptidases and their inhibitors: C01.013
PDB中UniProt可用的所有結構信息之概述：Q9UBR2 (Cathepsin Z) 在PDBe-KB。

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[1] .

[refGRCh38Ensembl-2] GRCh38: Ensembl release 89: ENSG00000101160 - Ensembl, May 2017

[refGRCm38Ensembl-3] GRCm38: Ensembl release 89: ENSMUSG00000016256 - Ensembl, May 2017

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9642240-6] Santamaría I, Velasco G, Pendás AM, Fueyo A, López-Otín C. . The Journal of Biological Chemistry. July 1998, 273 (27): 16816–23. PMID 9642240. doi:10.1074/jbc.273.27.16816 .

[entrez-7] . [2022-11-01]. （原始内容存档于2010-03-08）.

[pmid22024571-8] Turk V, Stoka V, Vasiljeva O, Renko M, Sun T, Turk B, Turk D. . Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. January 2012, 1824 (1): 68–88. PMC 7105208 . PMID 22024571. doi:10.1016/j.bbapap.2011.10.002 .

[pmid10504234-9] Nägler DK, Zhang R, Tam W, Sulea T, Purisima EO, Ménard R. . Biochemistry. September 1999, 38 (39): 12648–54. PMID 10504234. doi:10.1021/bi991371z.

[pmid9738465-10] Nägler DK, Ménard R. . FEBS Letters. August 1998, 434 (1–2): 135–9. PMID 9738465. S2CID 22899822. doi:10.1016/s0014-5793(98)00964-8 .

[pmid17065156-11] Lechner AM, Assfalg-Machleidt I, Zahler S, Stoeckelhuber M, Machleidt W, Jochum M, Nägler DK. . The Journal of Biological Chemistry. December 2006, 281 (51): 39588–97. PMID 17065156. doi:10.1074/jbc.M513439200 .

[pmid19262176-12] Kos J, Jevnikar Z, Obermajer N. . Cell Adhesion & Migration. April–June 2009, 3 (2): 164–6. PMC 2679876 . PMID 19262176. doi:10.4161/cam.3.2.7403.

[pmid18701767-13] Obermajer N, Svajger U, Bogyo M, Jeras M, Kos J. . Journal of Leukocyte Biology. November 2008, 84 (5): 1306–15. PMC 3252843 . PMID 18701767. doi:10.1189/jlb.0508285.

[pmid25274726-14] Akkari L, Gocheva V, Kester JC, Hunter KE, Quick ML, Sevenich L, Wang HW, Peters C, Tang LH, Klimstra DS, Reinheckel T, Joyce JA. . Genes & Development. October 2014, 28 (19): 2134–50. PMC 4180975 . PMID 25274726. doi:10.1101/gad.249599.114.

[pmid25433997-15] Teller A, Jechorek D, Hartig R, Adolf D, Reißig K, Roessner A, Franke S. . Pathology, Research and Practice. January 2015, 211 (1): 62–70. PMID 25433997. doi:10.1016/j.prp.2014.09.005.

[pmid23936173-16] Krueger S, Bernhardt A, Kalinski T, Baldensperger M, Zeh M, Teller A, Adolf D, Reinheckel T, Roessner A, Kuester D. . PLOS ONE. 2013, 8 (7): e70242. PMC 3728094 . PMID 23936173. doi:10.1371/journal.pone.0070242 .

[pmid23958447-17] Pišlar AH, Zidar N, Kikelj D, Kos J. . Neuropharmacology. July 2014, 82: 121–31. PMID 23958447. S2CID 22499368. doi:10.1016/j.neuropharm.2013.07.040.

[pmid21368909-18] Adams LA, Möller M, Nebel A, Schreiber S, van der Merwe L, van Helden PD, Hoal EG. . European Journal of Human Genetics. June 2011, 19 (6): 676–81. PMC 3110050 . PMID 21368909. doi:10.1038/ejhg.2011.1.

[19] . BioGRID. [6 August 2016]. （原始内容存档于2022-11-01）.

[pmid23621429-20] Hafner A, Glavan G, Obermajer N, Živin M, Schliebs R, Kos J. . Aging Cell. August 2013, 12 (4): 604–14. PMID 23621429. S2CID 23835547. doi:10.1111/acel.12093 .