组织蛋白酶K

组织蛋白酶K
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1MEM、3KWB、3KX1、4X6J、1AYW、3KW9、1YT7、1AU2、4X6H、1Q6K、1YK7、1ATK、3C9E、1AYV、1BGO、4N8W、7PCK、4DMX、4X6I、1NL6、1TU6、3O0U、1AU4、3OVZ、3KWZ、2ATO、3O1G、1AU0、1BY8、1SNK、2AUZ、4DMY、4N79、1AYU、1U9X、1YK8、1AU3、1U9V、2BDL、1VSN、1U9W、2AUX、2R6N、3H7D、1NLJ、5J94、4YVA、4YV8
識別號
别名	CTSK；, CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD, cathepsin K
外部ID	OMIM：601105 MGI：107823 HomoloGene：68053 GeneCards：CTSK
相關疾病
	pycnodysostosis[1]
為以下藥物的標靶
	odanacatib、odanacatib、balicatib[2]
基因位置（人类）
染色体	1號染色體[3]
终止	150,809,577 bp[3]
基因位置（小鼠）
染色体	小鼠3号染色体[4]
终止	95,416,673 bp[4]
RNA表达模式
	查阅更多表达数据
基因本體
分子功能	• fibronectin binding; • 半胱氨酸型肽酶活性; • collagen binding; • 肽酶活性; • 血浆蛋白结合; • cysteine-type endopeptidase activity; • 水解酶活性; • proteoglycan binding; • serine-type endopeptidase activity;
細胞組分	• 細胞質; • 細胞外區域; • endolysosome lumen; • 溶酶体; • 細胞外空間; • 核质; • 細胞內膜結合細胞器; • lysosomal lumen;
生物學過程	• 膜内成骨; • positive regulation of protein targeting to mitochondrion; • extracellular matrix disassembly; • 骨质吸收; • 蛋白酶解; • toll-like receptor signaling pathway; • regulation of autophagy of mitochondrion; • collagen catabolic process; • proteolysis involved in cellular protein catabolic process; • regulation of keratinocyte differentiation;
	Sources:Amigo / QuickGO
直系同源
	1513
	13038
	ENSG00000143387
	ENSMUSG00000028111
	P43235
	P55097
	NM_000396
	NM_007802
	NP_000387
	NP_031828
	維基數據

组织蛋白酶K（英语：Cathepsin K），是一种在人体中由CTSK基因编码的酶。[7][8]

功能

该基因编码的蛋白质是半胱氨酸组织蛋白酶，一种参与骨重塑和再吸收的溶酶体半胱氨酸蛋白酶。这种蛋白质是肽酶C1蛋白质家族的成员，主要在破骨细胞中表达。

组织蛋白酶K是一种蛋白酶，其特征在于其对激肽的高度特异性，与骨吸收有关。该酶分解代谢弹性蛋白、胶原蛋白和明胶的能力使其能够分解骨骼和软骨。这种分解代谢活动也是肺弹性丧失和肺气肿反冲的部分原因。组织蛋白酶K抑制剂在骨质疏松症的治疗中显示出巨大的潜力。在被称为受控组织蛋白酶同类相食的过程中，组织蛋白酶K被组织蛋白酶S降解。

组织蛋白酶K的表达受到组织损伤后释放的炎性细胞因子的刺激。

临床意义

组织蛋白酶K在很大一部分人类乳癌中表达，它可能有助于肿瘤侵袭性。[9]该基因的突变是致密性成骨不全症的原因，这是一种以骨质硬化和身材矮小为特征的常染色体隐性遗传病。[10]组织蛋白酶K也被发现在胶质母细胞瘤中过度表达。[11]

组织蛋白酶K的表达是某些癌症的特征，而其他癌症则没有。[12]组织蛋白酶K抗体已上市销售，用于研究该酶在各种细胞中的表达。[13][14][15]

默克公司在骨质疏松症的III期临床试验中使用了一种组织蛋白酶K抑制剂，奥达那替尼。2016年9月，默克公司在自行评估不良事件后宣布停止开发奥达那替尼，独立评估显示中风风险增加。[16][17]其他组织蛋白酶K抑制剂处于不同的发展阶段。[18][19]截至2017年10月，Medivir公司有一种组织蛋白酶K抑制剂MIV-711（L-006235[20][21][22]），在IIa期临床试验中，作为一种改善骨关节炎的药物。

参考文献

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图集

Osteoclast

外部链接

The MEROPS online database for peptidases and their inhibitors: C01.036
醫學主題詞表（MeSH）：Cathepsin+K

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[1] .

[2] .

[refGRCh38Ensembl-3] GRCh38: Ensembl release 89: ENSG00000143387 - Ensembl, May 2017

[refGRCm38Ensembl-4] GRCm38: Ensembl release 89: ENSMUSG00000028111 - Ensembl, May 2017

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

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

[entrez-7] .

[pmid7818555-8] Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T. . Biochemical and Biophysical Research Communications. January 1995, 206 (1): 89–96. PMID 7818555. doi:10.1006/bbrc.1995.1013.

[Duong_2014-9] Duong LT, Wesolowski GA, Leung P, Oballa R, Pickarski M. . Molecular Cancer Therapeutics. 23 September 2014, 13 (12): 2898–909 [2 October 2016]. PMID 25249554. doi:10.1158/1535-7163.MCT-14-0253 . （原始内容存档于2019-08-24）.

[NCBI_Gene_Card_cathepsin_K-10] . NCBI Gene. National Center for Biotechnology Information, U.S. National Library of Medicine. 4 September 2016 [2 October 2016]. （原始内容存档于2022-10-31）.

[van_Noorden_2014-11] Verbovšek U, Motaln H, Rotter A, Atai NA, Gruden K, Van Noorden CJ, Lah TT. . PLOS ONE. 30 October 2014, 9 (10): e111819. Bibcode:2014PLoSO...9k1819V. PMC 4214761 . PMID 25356585. doi:10.1371/journal.pone.0111819 .

[Argani_2013-12] Argani, Pedram; et al. . American Journal of Clinical Pathology. 1 February 2013, 139 (2): 151–159. PMC 3957187 . PMID 23355199. doi:10.1309/AJCPDTRTO2Z4UEXD.

[NovusBiologicals-13] . Novus Biologicals online catalog. Novus Biologicals, LLC. 2016 [2 October 2016]. （原始内容存档于2022-10-31）.

[Abcam_Catalog-14] . Abcam plc online catalog. Abcam plc. 2016 [2 October 2016]. （原始内容存档于2022-10-31）.

[Antibodies.com-15] . Antibodies.com online catalog. Antibodies.com Ltd. 2018 [16 January 2018]. （原始内容存档于2018-01-17）.

[Bromme2009-16] Brömme, Dieter; Lecaille, Fabien. . Expert Opinion on Investigational Drugs. 24 April 2009, 18 (5): 585–600. PMC 3110777 . PMID 19388876. doi:10.1517/13543780902832661.

[MerckFinancial-17] . Merck Sharp & Dohme Corp. 2 September 2016 [1 October 2016]. （原始内容存档于2016-11-09）.

[18] Asagiri M, Hirai T, Kunigami T, Kamano S, Gober HJ, Okamoto K, Nishikawa K, Latz E, Golenbock DT, Aoki K, Ohya K, Imai Y, Morishita Y, Miyazono K, Kato S, Saftig P, Takayanagi H,. (2008). Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science, 319(5863), 624-627.

[19] Hussein, H., Ishihara, A., Menendez, M., & Bertone, A. (2014). Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses. Journal of veterinary pharmacology and therapeutics.

[20] . www.medivir.se. [2017-10-06]. （原始内容存档于6 October 2017）（英语）.

[21] Burston JJ, Xu L, Mapp PI, Grabowska U, Tunblad K, Lindström E, Chapman V. (PDF). www.medivir.se. April 2016 [6 October 2017]. （原始内容 (PDF)存档于6 October 2017）.

[22] (PDF). mb.cision.com. 14 September 2017 [2022-10-31]. （原始内容存档 (PDF)于2022-08-21）.