Cathepsin K

CTSK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 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
Identifiers
Aliases	CTSK, CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD, cathepsin K
External IDs	OMIM: 601105 MGI: 107823 HomoloGene: 68053 GeneCards: CTSK
Targeted by Drug
odanacatib[1]
Gene ontology Molecular function • fibronectin binding • cysteine-type peptidase activity • collagen binding • peptidase activity • protein binding • cysteine-type endopeptidase activity • hydrolase activity • proteoglycan binding • serine-type endopeptidase activity Cellular component • cytoplasm • extracellular space • extracellular region • endolysosome lumen • lysosome Biological process • intramembranous ossification • positive regulation of protein targeting to mitochondrion • extracellular matrix disassembly • bone resorption • proteolysis • toll-like receptor signaling pathway • regulation of mitophagy • collagen catabolic process • proteolysis involved in cellular protein catabolic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1513	13038
Ensembl	ENSG00000143387	ENSMUSG00000028111
UniProt	P43235	P55097
RefSeq (mRNA)	NM_000396	NM_007802
RefSeq (protein)	NP_000387.1	NP_031828.2
Location (UCSC)	Chr 1: 150.8 – 150.81 Mb	Chr 3: 95.5 – 95.51 Mb
PubMed search	[2]	[3]
Wikidata

Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene.^[4][5]

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 expressed predominantly 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 show great potential in the treatment of osteoporosis. Cathepsin K is degraded by Cathepsin S, called Controlled Cathepsin Cannibalism.

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. ^[6] Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. ^[7] Cathepsin K has also been found to be over-expressed in glioblastoma. ^[8]

That the expression of Cathepsin K is characteristic for some cancers and not others has been documented. ^[9] Cathepsin K antibodies are marketed for research into expression of this enyzme by various cells. ^{[10] [11]}

Merck had a Cathepsin K inhibitor in Phase 3 clinical trials by the name of odanacatib for an expected indication of osteoporosis. On September 2, 2016, Merck announced they were discontinuing development of odanacatib after their own assessment of adverse events and an independent assessment showed increased risk of stroke in patients receiving odanacatib in Merck's Phase 3 clinical trials. ^{[12] [13]}

Velcura Therapeutics, Inc. has also developed a highly selective cathepsin K inhibitor named VEL-0230 and has been tested in human, rat, equine clinical trials. ^{[14] [15] [16]}

References

Further reading

Additional images

• 

  Osteoclast

External links

• The MEROPS online database for peptidases and their inhibitors: C01.036
• Cathepsin K at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1atk: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH THE COVALENT INHIBITOR E-64  1au0: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC DIACYLAMINOMETHYL KETONE INHIBITOR  1au2: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PROPANONE INHIBITOR  1au3: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PYRROLIDINONE INHIBITOR  1au4: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PYRROLIDINONE INHIBITOR  1ayu: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT SYMMETRIC BISCARBOHYDRAZIDE INHIBITOR  1ayv: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT THIAZOLHYDRAZIDE INHIBITOR  1ayw: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT BENZYLOXYBENZOYLCARBOHYDRAZIDE INHIBITOR  1bgo: CRYSTAL STRUCTURE OF CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT PEPTIDOMIMETIC INHIBITOR  1by8: THE CRYSTAL STRUCTURE OF HUMAN PROCATHEPSIN K  1mem: CRYSTAL STRUCTURE OF CATHEPSIN K COMPLEXED WITH A POTENT VINYL SULFONE INHIBITOR  1nl6: Crystal Structure Of The Cysteine Protease Human Cathepsin K In Complex With A Covalent Azepanone Inhibitor  1nlj: CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT AZEPANONE INHIBITOR  1q6k: Cathepsin K complexed with t-butyl(1S)-1-cyclohexyl-2-oxoethylcarbamate  1snk: Cathepsin K complexed with carbamate derivatized norleucine aldehyde  1tu6: Cathepsin K complexed with a ketoamide inhibitor  1u9v: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABE854  1u9w: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABI491  1u9x: Crystal Structure of the Cysteine Protease Human Cathepsin K in Complex with the Covalent Inhibitor NVP-ABJ688  1vsn: Crystal structure of a potent small molecule inhibitor bound to cathepsin K  1yk7: Cathepsin K complexed with a cyanopyrrolidine inhibitor  1yk8: Cathepsin K complexed with a cyanamide-based inhibitor  1yt7: Cathepsin K complexed with a constrained ketoamide inhibitor  2ato: Crystal structure of Human Cathepsin K in complex with myocrisin  2aux: Cathepsin K complexed with a semicarbazone inhibitor  2auz: Cathepsin K complexed with a semicarbazone inhibitor  2bdl: Cathepsin K complexed with a pyrrolidine ketoamide-based inhibitor  2f7d: A mutant rabbit cathepsin K with a nitrile inhibitor  2ftd: Crystal structure of Cathepsin K complexed with 7-Methyl-Substituted Azepan-3-one compound  7pck: CRYSTAL STRUCTURE OF WILD TYPE HUMAN PROCATHEPSIN K