組織蛋白酶K

組織蛋白酶K
已知的結構
PDB	直系同源搜尋: 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
別名	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
為以下藥物的標靶
	odanacatib、odanacatib、balicatib
基因位置（人類）
染色體	1號染色體
終止	150,809,577 bp
基因位置（小鼠）
染色體	小鼠3號染色體
終止	95,416,673 bp
RNA表達模式
	查閱更多表達數據
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; • 血漿蛋白結合; • 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; • 溶酶體; • 細胞外空間; • 核質; • 細胞內膜結合細胞器; • lysosomal lumen;
生物學過程	• 膜內成骨; • positive regulation of protein targeting to mitochondrion; • extracellular matrix disassembly; • 骨質吸收; • 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
檢視/編輯人類	檢視/編輯小鼠

組織蛋白酶K（英語：Cathepsin K），是一種在人體中由CTSK基因編碼的酶。^[7]^[8]

功能

該基因編碼的蛋白質是半胱氨酸組織蛋白酶，一種參與骨重塑和再吸收的溶酶體半胱氨酸蛋白酶。這種蛋白質是肽酶C1蛋白質家族的成員，主要在破骨細胞中表達。

組織蛋白酶K是一種蛋白酶，其特徵在於其對激肽的高度特異性，與骨吸收有關。該酶分解代謝彈性蛋白、膠原蛋白和明膠的能力使其能夠分解骨骼和軟骨。這種分解代謝活動也是肺彈性喪失和肺氣腫反衝的部分原因。組織蛋白酶K抑制劑在骨質疏鬆症的治療中顯示出巨大的潛力。在被稱為受控組織蛋白酶同類相食的過程中，組織蛋白酶K被組織蛋白酶S降解。

組織蛋白酶K的表達受到組織損傷後釋放的炎性細胞因子的刺激。

臨床意義

組織蛋白酶K在很大一部分人類乳癌中表達，它可能有助於腫瘤侵襲性。^[9]該基因的突變是緻密性成骨不全症的原因，這是一種以骨質硬化和身材矮小為特徵的常染色體隱性遺傳病。^[10]組織蛋白酶K也被發現在膠質母細胞瘤中過度表達。^[11]

組織蛋白酶K的表達是某些癌症的特徵，而其他癌症則沒有。^[12]組織蛋白酶K抗體已上市銷售，用於研究該酶在各種細胞中的表達。^[13]^[14]^[15]

默克公司在骨質疏鬆症的III期臨床試驗中使用了一種組織蛋白酶K抑制劑，奧達那替尼。2016年9月，默克公司在自行評估不良事件後宣佈停止開發奧達那替尼，獨立評估顯示中風風險增加。^[16]^[17]其他組織蛋白酶K抑制劑處於不同的發展階段。^[18]^[19]截至2017年10月，Medivir公司有一種組織蛋白酶K抑制劑MIV-711（L-006235^[20]^[21]^[22]），在IIa期臨床試驗中，作為一種改善骨關節炎的藥物。

參考文獻

^ 與组织蛋白酶K相關的疾病；在維基數據上查看/編輯參考.
^ 對Cathepsin K起作用的藥物；在維基數據上查看/編輯參考.
^ ^3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000143387 - Ensembl, May 2017
^ ^4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000028111 - 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.
^ Entrez Gene: CTSK cathepsin K.
^ Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T. Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone. Biochemical and Biophysical Research Communications. January 1995, 206 (1): 89–96. PMID 7818555. doi:10.1006/bbrc.1995.1013.
^ Duong LT, Wesolowski GA, Leung P, Oballa R, Pickarski M. Efficacy of a Cathepsin K Inhibitor in a Preclinical Model for Prevention and Treatment of Breast Cancer Bone Metastasis. Molecular Cancer Therapeutics. 23 September 2014, 13 (12): 2898–909 [2 October 2016]. PMID 25249554. doi:10.1158/1535-7163.MCT-14-0253 . （原始內容存檔於2019-08-24）.
^ CTSK cathepsin K [ Homo sapiens (human) ]. NCBI Gene. National Center for Biotechnology Information, U.S. National Library of Medicine. 4 September 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.
^ Verbovšek U, Motaln H, Rotter A, Atai NA, Gruden K, Van Noorden CJ, Lah TT. Expression Analysis of All Protease Genes Reveals Cathepsin K to Be Overexpressed in Glioblastoma. PLOS ONE. 30 October 2014, 9 (10): e111819. Bibcode:2014PLoSO...9k1819V. PMC 4214761 . PMID 25356585. doi:10.1371/journal.pone.0111819 .
^ Argani, Pedram; et al. A Broad Survey of Cathepsin K Immunoreactivity in Human Neoplasms. American Journal of Clinical Pathology. 1 February 2013, 139 (2): 151–159. PMC 3957187 . PMID 23355199. doi:10.1309/AJCPDTRTO2Z4UEXD.
^ Cathepsin K Antibodies. Novus Biologicals online catalog. Novus Biologicals, LLC. 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.
^ Anti-Cathepsin K antibody (ab19027). Abcam plc online catalog. Abcam plc. 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.
^ Anti-Cathepsin K Antibody (A5871). Antibodies.com online catalog. Antibodies.com Ltd. 2018 [16 January 2018]. （原始內容存檔於2018-01-17）.
^ Brömme, Dieter; Lecaille, Fabien. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opinion on Investigational Drugs. 24 April 2009, 18 (5): 585–600. PMC 3110777 . PMID 19388876. doi:10.1517/13543780902832661.
^ Merck Provides Update on Odanacatib Development Program. Merck Sharp & Dohme Corp. 2 September 2016 [1 October 2016]. （原始內容存檔於2016-11-09）.
^ 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.
^ 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.
^ MIV-711 for the treatment of ostheoarthritis. www.medivir.se. [2017-10-06]. （原始內容存檔於6 October 2017）（英語）.
^ Burston JJ, Xu L, Mapp PI, Grabowska U, Tunblad K, Lindström E, Chapman V. The Cathepsin K Inhibitor L-006235 Demonstrates Both Disease Modification and Attenuation of Pain Behaviour in the in the Mia Model of Osteoarthritis (PDF). www.medivir.se. April 2016 [6 October 2017]. （原始內容 (PDF)存檔於6 October 2017）.
^ Data monitoring committee gives "Go Ahead" in the MIV-711 osteoarthritis extension study (PDF). mb.cision.com. 14 September 2017 [2022-10-31]. （原始內容存檔 (PDF)於2022-08-21）.

閱讀

Motyckova G, Fisher DE. Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease.. Current Molecular Medicine. 2003, 2 (5): 407–21. PMID 12125807. doi:10.2174/1566524023362401.
Troen BR. The regulation of cathepsin K gene expression.. Annals of the New York Academy of Sciences. 2006, 1068 (1): 165–72. Bibcode:2006NYASA1068..165T. PMID 16831915. S2CID 8117602. doi:10.1196/annals.1346.018.
Del Nery E, Chagas JR, Juliano MA, et al. Evaluation of the extent of the binding site in human tissue kallikrein by synthetic substrates with sequences of human kininogen fragments.. The Biochemical Journal. 1996, 312 (1): 233–8. PMC 1136249 . PMID 7492318. doi:10.1042/bj3120233.
Brömme D, Okamoto K. Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution.. Biological Chemistry Hoppe-Seyler. 1995, 376 (6): 379–84. PMID 7576232. doi:10.1515/bchm3.1995.376.6.379.
Gelb BD, Edelson JG, Desnick RJ. Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping.. Nature Genetics. 1995, 10 (2): 235–7. PMID 7663521. S2CID 24297764. doi:10.1038/ng0695-235.
Polymeropoulos MH, Ortiz De Luna RI, Ide SE, et al. The gene for pycnodysostosis maps to human chromosome 1cen-q21.. Nature Genetics. 1995, 10 (2): 238–9 [2022-10-31]. PMID 7663522. S2CID 11723845. doi:10.1038/ng0695-238. （原始內容存檔於2022-10-31）.
Shi GP, Chapman HA, Bhairi SM, et al. Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2. (PDF). FEBS Letters. 1995, 357 (2): 129–34. PMID 7805878. S2CID 28099876. doi:10.1016/0014-5793(94)01349-6 .
Inaoka T, Bilbe G, Ishibashi O, et al. Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone.. Biochemical and Biophysical Research Communications. 1995, 206 (1): 89–96. PMID 7818555. doi:10.1006/bbrc.1995.1013.
Velasco G, Ferrando AA, Puente XS, et al. Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues.. The Journal of Biological Chemistry. 1994, 269 (43): 27136–42. PMID 7929457. doi:10.1016/S0021-9258(18)47135-9 .
Li YP, Alexander M, Wucherpfennig AL, et al. Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas.. Journal of Bone and Mineral Research. 1996, 10 (8): 1197–202. PMID 8585423. S2CID 41832979. doi:10.1002/jbmr.5650100809.
Bossard MJ, Tomaszek TA, Thompson SK, et al. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.. Journal of Biological Chemistry. 1996, 271 (21): 12517–24. PMID 8647860. doi:10.1074/jbc.271.21.12517 .
Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.. Science. 1996, 273 (5279): 1236–8. Bibcode:1996Sci...273.1236G. PMID 8703060. S2CID 7188076. doi:10.1126/science.273.5279.1236.
Johnson MR, Polymeropoulos MH, Vos HL, et al. A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis.. Genome Research. 1997, 6 (11): 1050–5. PMID 8938428. doi:10.1101/gr.6.11.1050 .
Littlewood-Evans A, Kokubo T, Ishibashi O, et al. Localization of cathepsin K in human osteoclasts by in situ hybridization and immunohistochemistry.. Bone. 1997, 20 (2): 81–6. PMID 9028530. doi:10.1016/S8756-3282(96)00351-1.
McGrath ME, Klaus JL, Barnes MG, Brömme D. Crystal structure of human cathepsin K complexed with a potent inhibitor.. Nature Structural Biology. 1997, 4 (2): 105–9. PMID 9033587. S2CID 22175354. doi:10.1038/nsb0297-105.
Rood JA, Van Horn S, Drake FH, et al. Genomic organization and chromosome localization of the human cathepsin K gene (CTSK).. Genomics. 1997, 41 (2): 169–76. PMID 9143491. doi:10.1006/geno.1997.4614.
Gelb BD, Shi GP, Heller M, et al. Structure and chromosomal assignment of the human cathepsin K gene.. Genomics. 1997, 41 (2): 258–62. PMID 9143502. doi:10.1006/geno.1997.4631.
Gomes RA, Juliano L, Chagas JR, Hial V. Characterization of kininogenase activity of an acidic proteinase isolated from human kidney.. Canadian Journal of Physiology and Pharmacology. 1997, 75 (6): 757–61. PMID 9276160. doi:10.1139/cjpp-75-6-757.
Thompson SK, Halbert SM, Bossard MJ, et al. Design of potent and selective human cathepsin K inhibitors that span the active site.. Proceedings of the National Academy of Sciences. 1998, 94 (26): 14249–54. PMC 24926 . PMID 9405598. doi:10.1073/pnas.94.26.14249 .
Gelb BD, Willner JP, Dunn TM, et al. Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis.. The American Journal of Human Genetics. 1998, 62 (4): 848–54. PMC 1377035 . PMID 9529353. doi:10.1086/301795.

圖集

Osteoclast

外部連結

The MEROPS online database for peptidases and their inhibitors: C01.036^{[失效連結]}
醫學主題詞表（MeSH）：Cathepsin+K

[1] 與组织蛋白酶K相關的疾病；在維基數據上查看/編輯參考.

[2] 對Cathepsin K起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000143387 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000028111 - Ensembl, May 2017

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

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

[entrez-7] Entrez Gene: CTSK cathepsin K.

[pmid7818555-8] Inaoka T, Bilbe G, Ishibashi O, Tezuka K, Kumegawa M, Kokubo T. Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone. 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. Efficacy of a Cathepsin K Inhibitor in a Preclinical Model for Prevention and Treatment of Breast Cancer Bone Metastasis. Molecular Cancer Therapeutics. 23 September 2014, 13 (12): 2898–909 [2 October 2016]. PMID 25249554. doi:10.1158/1535-7163.MCT-14-0253 . （原始內容存檔於2019-08-24）.

[NCBI_Gene_Card_cathepsin_K-10] CTSK cathepsin K [ Homo sapiens (human) ]. NCBI Gene. National Center for Biotechnology Information, U.S. National Library of Medicine. 4 September 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.

[van_Noorden_2014-11] Verbovšek U, Motaln H, Rotter A, Atai NA, Gruden K, Van Noorden CJ, Lah TT. Expression Analysis of All Protease Genes Reveals Cathepsin K to Be Overexpressed in Glioblastoma. 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. A Broad Survey of Cathepsin K Immunoreactivity in Human Neoplasms. American Journal of Clinical Pathology. 1 February 2013, 139 (2): 151–159. PMC 3957187 . PMID 23355199. doi:10.1309/AJCPDTRTO2Z4UEXD.

[NovusBiologicals-13] Cathepsin K Antibodies. Novus Biologicals online catalog. Novus Biologicals, LLC. 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.

[Abcam_Catalog-14] Anti-Cathepsin K antibody (ab19027). Abcam plc online catalog. Abcam plc. 2016 [2 October 2016]. （原始內容存檔於2022-10-31）.

[Antibodies.com-15] Anti-Cathepsin K Antibody (A5871). Antibodies.com online catalog. Antibodies.com Ltd. 2018 [16 January 2018]. （原始內容存檔於2018-01-17）.

[Bromme2009-16] Brömme, Dieter; Lecaille, Fabien. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opinion on Investigational Drugs. 24 April 2009, 18 (5): 585–600. PMC 3110777 . PMID 19388876. doi:10.1517/13543780902832661.

[MerckFinancial-17] Merck Provides Update on Odanacatib Development Program. Merck Sharp & Dohme Corp. 2 September 2016 [1 October 2016]. （原始內容存檔於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] MIV-711 for the treatment of ostheoarthritis. www.medivir.se. [2017-10-06]. （原始內容存檔於6 October 2017）（英語）.

[21] Burston JJ, Xu L, Mapp PI, Grabowska U, Tunblad K, Lindström E, Chapman V. The Cathepsin K Inhibitor L-006235 Demonstrates Both Disease Modification and Attenuation of Pain Behaviour in the in the Mia Model of Osteoarthritis (PDF). www.medivir.se. April 2016 [6 October 2017]. （原始內容 (PDF)存檔於6 October 2017）.

[22] Data monitoring committee gives "Go Ahead" in the MIV-711 osteoarthritis extension study (PDF). mb.cision.com. 14 September 2017 [2022-10-31]. （原始內容存檔 (PDF)於2022-08-21）.

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閱論編蛋白酶類：半胱氨酸蛋白酶類（EC 3.4.22)
胱天蛋白酶	胱天蛋白酶1 胱天蛋白酶2 胱天蛋白酶3 胱天蛋白酶4 胱天蛋白酶5 胱天蛋白酶6 胱天蛋白酶7 胱天蛋白酶8 胱天蛋白酶9 胱天蛋白酶10 胱天蛋白酶11 胱天蛋白酶12 胱天蛋白酶13 胱天蛋白酶14
來自果實	木瓜蛋白酶無花果蛋白酶（英語：Ficain）鳳梨蛋白酶獼猴桃蛋白酶
鈣蛋白酶	CAPN1 CAPN2 CAPN3 CAPN5 CAPN6 CAPN7 CAPN8 CAPN9 CAPN10 CAPN11 CAPN12 CAPN13 CAPN14 CAPNS1 CAPNS2
組織蛋白酶	B C F H K L1/L2 O S T W Z
其它	梭菌蛋白酶癌性促凝物質分離酶（英語：Separase） Autophagin Cruzipain 3C樣蛋白酶
EC 1.1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20/21/22 · 2.1/2/3/4/5/6/7(2.7.10/11-12)/8/9 · 3.1/2/3/4(3.4.21/22/23/24)/5/6/7/8/9/10/11/12/13 · 4.1/2/3/4/5/6 · 5.1/2/3/4/5/99 · 6.1-3（英語：Template:Ligases CO CS and CN）/4/5-6

閱論編酶
活性	活性位點結合位點催化三聯體負氧離子洞酶催化混雜（英語：Enzyme promiscuity）催化最適酶（英語：Catalytically perfect enzyme）輔因子輔酶酶促反應
調節	變構調節協同性（英語：Cooperativity）酶抑制劑酶活化劑
分類	EC編號蛋白質超家族蛋白質家族酶列表
動力學	酶動力學伊迪-霍夫斯蒂圖（英語：Eadie–Hofstee diagram）哈尼斯-伍爾夫圖（英語：Hanes–Woolf plot）雙倒數圖米氏動力學
類型	EC1 氧化還原酶（列表（英語：List of EC numbers (EC 1)）） EC2 轉移酶（列表（英語：List of EC numbers (EC 2)）） EC3 水解酶（列表（英語：List of EC numbers (EC 3)）） EC4 裂解酶（列表（英語：List of EC numbers (EC 4)）） EC5 異構酶（列表（英語：List of EC numbers (EC 5)）） EC6 連接酶（列表（英語：List of EC numbers (EC 6)）） EC7 移位酶（英語：Translocase）（列表（英語：List of EC numbers (EC 7)））