Cathepsin K
| Cathepsin K |
Ribbon diagram of cathepsin K, colored by secondary structure. From PDB 1TU6. |
| Available structures |
| PDB |
1ATK, 1AU0, 1AU2, 1AU3, 1AU4, 1AYU, 1AYV, 1AYW, 1BY8, 1MEM, 1NL6, 1NLJ, 1Q6K, 1SNK, 1TU6, 1U9V, 1U9W, 1U9X, 1VSN, 1YK7, 1YK8, 1YT7, 2ATO, 2AUX, 2AUZ, 2BDL, 2R6N, 3C9E, 3H7D, 3KW9, 3KWB, 3KWZ, 3KX1, 3O1G, 7PCK |
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| Identifiers |
| Symbols |
CTSK; CTS02; CTSO; CTSO1; CTSO2; MGC23107; PKND; PYCD |
| External IDs |
OMIM: 601105 MGI: 107823 HomoloGene: 68053 GeneCards: CTSK Gene |
| EC number |
3.4.22.38 |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
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| Entrez |
1513 |
13038 |
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| Ensembl |
ENSG00000143387 |
ENSMUSG00000028111 |
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| UniProt |
P43235 |
Q545T0 |
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| RefSeq (mRNA) |
NM_000396.3 |
NM_007802.3 |
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| RefSeq (protein) |
NP_000387.1 |
NP_031828.2 |
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| Location (UCSC) |
Chr 1:
150.77 – 150.78 Mb |
Chr 3:
95.3 – 95.31 Mb |
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| PubMed search |
[1] |
[2] |
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Cathepsin K, abbreviated CTSK, is an enzyme which in humans is encoded by the CTSK gene.[1][2]
Function
The protein encoded by this gene is a lysosomal cysteine protease involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts.
Cathepsin K is a protease, which is defined by its high specificity for kinins, that is involved in bone resorption. The enzyme's ability to catabolize elastin, collagen, and gelatin allow it to break down bone and cartilage. This catabolic activity is also partially responsible for the loss of lung elasticity and recoil in emphysema. Cathepsin K inhibitors, such as odanacatib, show great potential in the treatment of osteoporosis.
Cathepsin K expression is stimulated by inflammatory cytokines that are released after tissue injury.
Clinical significance
Cathepsin K is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature.
References
Further reading
- Motyckova G, Fisher DE (2003). "Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease.". Curr. Mol. Med. 2 (5): 407–21. doi:10.2174/1566524023362401. PMID 12125807.
- Troen BR (2006). "The regulation of cathepsin K gene expression.". Ann. N. Y. Acad. Sci. 1068: 165–72. doi:10.1196/annals.1346.018. PMID 16831915.
- Del Nery E, Chagas JR, Juliano MA, et al. (1996). "Evaluation of the extent of the binding site in human tissue kallikrein by synthetic substrates with sequences of human kininogen fragments.". Biochem. J. 312 ( Pt 1): 233–8. PMC 1136249. PMID 7492318. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1136249.
- Brömme D, Okamoto K (1995). "Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution.". Biol. Chem. Hoppe-Seyler 376 (6): 379–84. PMID 7576232.
- Gelb BD, Edelson JG, Desnick RJ (1995). "Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping.". Nat. Genet. 10 (2): 235–7. doi:10.1038/ng0695-235. PMID 7663521.
- Polymeropoulos MH, Ortiz De Luna RI, Ide SE, et al. (1995). "The gene for pycnodysostosis maps to human chromosome 1cen-q21.". Nat. Genet. 10 (2): 238–9. doi:10.1038/ng0695-238. PMID 7663522.
- Shi GP, Chapman HA, Bhairi SM, et al. (1995). "Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2.". FEBS Lett. 357 (2): 129–34. doi:10.1016/0014-5793(94)01349-6. PMID 7805878.
- Inaoka T, Bilbe G, Ishibashi O, et al. (1995). "Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone.". Biochem. Biophys. Res. Commun. 206 (1): 89–96. doi:10.1006/bbrc.1995.1013. PMID 7818555.
- Velasco G, Ferrando AA, Puente XS, et al. (1994). "Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues.". J. Biol. Chem. 269 (43): 27136–42. PMID 7929457.
- Li YP, Alexander M, Wucherpfennig AL, et al. (1996). "Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas.". J. Bone Miner. Res. 10 (8): 1197–202. doi:10.1002/jbmr.5650100809. PMID 8585423.
- Bossard MJ, Tomaszek TA, Thompson SK, et al. (1996). "Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.". J. Biol. Chem. 271 (21): 12517–24. doi:10.1074/jbc.271.21.12517. PMID 8647860.
- Gelb BD, Shi GP, Chapman HA, Desnick RJ (1996). "Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.". Science 273 (5279): 1236–8. doi:10.1126/science.273.5279.1236. PMID 8703060.
- Johnson MR, Polymeropoulos MH, Vos HL, et al. (1997). "A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis.". Genome Res. 6 (11): 1050–5. doi:10.1101/gr.6.11.1050. PMID 8938428.
- Littlewood-Evans A, Kokubo T, Ishibashi O, et al. (1997). "Localization of cathepsin K in human osteoclasts by in situ hybridization and immunohistochemistry.". Bone 20 (2): 81–6. doi:10.1016/S8756-3282(96)00351-1. PMID 9028530.
- McGrath ME, Klaus JL, Barnes MG, Brömme D (1997). "Crystal structure of human cathepsin K complexed with a potent inhibitor.". Nat. Struct. Biol. 4 (2): 105–9. doi:10.1038/nsb0297-105. PMID 9033587.
- Rood JA, Van Horn S, Drake FH, et al. (1997). "Genomic organization and chromosome localization of the human cathepsin K gene (CTSK).". Genomics 41 (2): 169–76. doi:10.1006/geno.1997.4614. PMID 9143491.
- Gelb BD, Shi GP, Heller M, et al. (1997). "Structure and chromosomal assignment of the human cathepsin K gene.". Genomics 41 (2): 258–62. doi:10.1006/geno.1997.4631. PMID 9143502.
- Gomes RA, Juliano L, Chagas JR, Hial V (1997). "Characterization of kininogenase activity of an acidic proteinase isolated from human kidney.". Can. J. Physiol. Pharmacol. 75 (6): 757–61. doi:10.1139/cjpp-75-6-757. PMID 9276160.
- Thompson SK, Halbert SM, Bossard MJ, et al. (1998). "Design of potent and selective human cathepsin K inhibitors that span the active site.". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14249–54. doi:10.1073/pnas.94.26.14249. PMC 24926. PMID 9405598. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24926.
- Gelb BD, Willner JP, Dunn TM, et al. (1998). "Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis.". Am. J. Hum. Genet. 62 (4): 848–54. doi:10.1086/301795. PMC 1377035. PMID 9529353. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1377035.
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PDB gallery
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1atk: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH THE COVALENT INHIBITOR E-64
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1au0: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC DIACYLAMINOMETHYL KETONE INHIBITOR
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1au2: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PROPANONE INHIBITOR
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1au3: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PYRROLIDINONE INHIBITOR
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1au4: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PYRROLIDINONE INHIBITOR
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1ayu: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC BISCARBOHYDRAZIDE INHIBITOR
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1ayv: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT THIAZOLHYDRAZIDE INHIBITOR
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1ayw: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT BENZYLOXYBENZOYLCARBOHYDRAZIDE INHIBITOR
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1bgo: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PEPTIDOMIMETIC INHIBITOR
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1by8: THE CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN K
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1mem: CRYSTAL STRUCTURE OF CATHEPSIN K COMPLEXED WITH A POTENT VINYL SULFONE INHIBITOR
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1nl6: Crystal Structure Of The Cysteine Protease Human Cathepsin K In Complex With A Covalent Azepanone Inhibitor
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1nlj: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT AZEPANONE INHIBITOR
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1q6k: Cathepsin K complexed with t-butyl(1S)-1-cyclohexyl-2-oxoethylcarbamate
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1snk: Cathepsin K complexed with carbamate derivatized norleucine aldehyde
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1tu6: Cathepsin K complexed with a ketoamide inhibitor
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1u9v: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABE854
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1u9w: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491
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1u9x: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABJ688
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1vsn: Crystal structure of a potent small molecule inhibitor bound to cathepsin K
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1yk7: Cathepsin K complexed with a cyanopyrrolidine inhibitor
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1yk8: Cathepsin K complexed with a cyanamide-based inhibitor
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1yt7: Cathepsin K complexed with a constrained ketoamide inhibitor
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2ato: Crystal structure of Human Cathepsin K in complex with myocrisin
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2aux: Cathepsin K complexed with a semicarbazone inhibitor
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2auz: Cathepsin K complexed with a semicarbazone inhibitor
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2bdl: Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor
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2f7d: A mutant rabbit cathepsin K with a nitrile inhibitor
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2ftd: Crystal structure of Cathepsin K complexed with 7-Methyl-Substituted Azepan-3-one compound
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7pck: CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K
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Additional images
External links
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| Caspase |
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| Fruit-derived |
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| Calpain |
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| Cathepsin |
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| Other |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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