Cathepsin K

Function

Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen.

Classification

Family (Pfam)

PF08246 Inhibitor_I29, PF00112 Peptidase_C1

InterPro

Papain-like_cys_pep_sf, Pept_asp_AS, Pept_cys_AS, Pept_his_AS, Peptidase_C1A, Peptidase_C1A_C, Peptidase_C1A_papain-like, Prot_inhib_I29

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 70

• 1ATK X-ray 2.20A
• 1AU0 X-ray 2.60A
• 1AU2 X-ray 2.60A
• 1AU3 X-ray 2.50A
• 1AU4 X-ray 2.30A
• 1AYU X-ray 2.20A
• 1AYV X-ray 2.30A
• 1AYW X-ray 2.40A
• 1BGO X-ray 2.30A
• 1BY8 X-ray 2.60A
• 1MEM X-ray 1.80A
• 1NL6 X-ray 2.80A
• … and 58 more

A predicted model is available from AlphaFold.

Gene Ontology · 19

• GO:0016324 apical plasma membrane
• GO:0036021 endolysosome lumen
• GO:0009897 external side of plasma membrane
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0043202 lysosomal lumen
• GO:0005764 lysosome
• GO:0005518 collagen binding
• GO:0004197 cysteine-type endopeptidase activity
• GO:0008234 cysteine-type peptidase activity
• GO:0001968 fibronectin binding
• GO:0043394 proteoglycan binding
• GO:0004252 serine-type endopeptidase activity
• GO:0030574 collagen catabolic process
• GO:0022617 extracellular matrix disassembly
• GO:0000423 mitophagy
• GO:0006508 proteolysis
• GO:0051603 proteolysis involved in protein catabolic process
• GO:0006590 thyroid hormone generation

Disease associations

• pycnodysostosis MONDO:0009940

Drugs targeting this protein · 2

• BALICATIB inhibitor
• ODANACATIB inhibitor

Related proteins · sequence + function similarity

• Cathepsin K 1.00
• Cathepsin K 1.00
• Cathepsin K 1.00
• Cathepsin K 1.00
• Cathepsin K 0.99
• Cathepsin K 0.99
• Cathepsin K 0.98
• Cathepsin K 0.98
• Procathepsin L 0.94
• Procathepsin L 0.94
• Cathepsin L2 0.94
• Cathepsin 8 0.94

Co-cited proteins · studied together in the literature

• Cathepsin K 1 shared papers
• Thyroglobulin 1 shared papers
• Thyroglobulin 1 shared papers

Literature · 17 cited papers

• Dental Abnormalities Caused by Novel Compound Heterozygous CTSK Mutations. J. Dent. Res. · 2015
• Novel Compound Heterozygous Mutations in the Cathepsin K Gene in Japanese Female Siblings with Pyknodysostosis. Mol. Syndromol. · 2012
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J. Cell Sci. · 2000
• Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population. Eur. J. Hum. Genet. · 2000
• Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J. Bone Miner. Res. · 1999
• Crystal structure of wild-type human procathepsin K. Protein Sci. · 1999
• The crystal structure of human procathepsin K. Biochemistry · 1999
• Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis. Am. J. Hum. Genet. · 1998
• Design of potent and selective human cathepsin K inhibitors that span the active site. Proc. Natl. Acad. Sci. U.S.A. · 1997
• Crystal structure of human cathepsin K complexed with a potent inhibitor. Nat. Struct. Biol. · 1997
• … and 5 more in the literature graph