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
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q21.3 Start 150,794,880 bp[1] End 150,809,577 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F2.1|3 40.74 cM Start 95,406,567 bp[2] End 95,416,673 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber stromal cell of endometrium gallbladder tibia gastric mucosa canal of the cervix Achilles tendon skin of abdomen vulva smooth muscle tissue Top expressed in body of femur calvaria ankle ankle joint molar dermis conjunctival fornix skin of abdomen lip cervix More reference expression data BioGPS More reference expression data
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 region endolysosome lumen lysosome extracellular space nucleoplasm intracellular membrane-bounded organelle lysosomal lumen Biological process intramembranous ossification positive regulation of protein targeting to mitochondrion extracellular matrix disassembly bone resorption proteolysis 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
Orthologs Species Human Mouse Entrez 1513 13038 Ensembl ENSG00000143387 ENSMUSG00000028111 UniProt P43235 P55097 RefSeq (mRNA) NM_000396 NM_007802 RefSeq (protein) NP_000387 NP_031828 Location (UCSC) Chr 1: 150.79 – 150.81 Mb Chr 3: 95.41 – 95.42 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene.^[5][6]

Function

The protein encoded by this gene is a cysteine cathepsin, 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 allows 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, in a process referred to as Controlled Cathepsin Cannibalism.

Cathepsin K expression is stimulated by inflammatory cytokines that are released after tissue injury.

Clinical significance

Cathepsin K is expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness.^[7] Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature.^[8] Cathepsin K has also been found to be over-expressed in glioblastoma.^[9]

That the expression of cathepsin K is characteristic for some cancers and not others has been documented.^[10] Cathepsin K antibodies are marketed for research into expression of this enzyme by various cells.^[11][12][13]

Merck had a cathepsin K inhibitor, odanacatib, in Phase III clinical trials for osteoporosis. In September, 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.^[14][15] Other cathepsin K inhibitors are in various stages of development.^[16][17][18] Medivir has a cathepsin K inhibitor, MIV-711 (L-006235^[19][20][21]), in Phase IIa clinical trial, as a disease modifying osteoarthritis drug, as of October 2017.

References

Further reading

Additional images

• 
  Osteoclast

External links

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