Summary for peptidase C01.036: cathepsin K

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Namecathepsin K
Other namescathepsin O [obs.], cathepsin O2 [obs.], cathepsin X [obs.]
Domain architecture
MEROPS Classification
Classification Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.036
Holotypecathepsin K (Homo sapiens), Uniprot accession P43235 (peptidase unit: 115-329), MERNUM MER0000644
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeCysteine
PeplistIncluded in the Peplist with identifier PL00063
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.38
EnzymologyBRENDA database
Proteolytic eventsCutDB database (11 cleavages)
Activity statushuman: active (Bromme, 2004)
mouse: active (Lecaille et al., 2003)
PhysiologyDegrades the organic matrix of bone in osteoclastic bone resorption.
KnockoutHereditary deficiency in human patients leads to pycnodysostosis, a rare, autosomal recessive skeletal dysplasia characterized by short stature, wide cranial sutures, and increased bone density and fragility (Gelb et al., 1996; Johnson et al., 1996; Hou et al., 1999). In cathepsin K-deficient mice, impaired osteoclastic bone resorption leads to osteopetrosis (Saftig et al., 1998).
Pharmaceutical relevancePotential drug target for control of osteoporosis (Troen, 2004) and perhaps emphysema.
Pathways KEGGLysosome
KEGGOsteoclast differentiation
KEGGRheumatoid arthritis
KEGGToll-like receptor signaling pathway
Other databases WIKIPEDIAhttp://en.wikipedia.org/wiki/Cathepsin_K
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/lpv/eaScissile bond-/-/-/- (based on 182 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 8 21 0 25 35 19 12 13
Pro 4 16 36 0 0 11 17 14
Ala 7 6 10 33 12 20 5 7
Val 11 1 25 2 5 12 9 9
Leu 21 8 60 1 5 9 8 17
Ile 3 13 13 1 22 5 12 15
Met 3 2 3 3 2 2 1 0
Phe 3 6 12 1 7 6 5 7
Tyr 8 12 5 0 0 1 5 0
Trp 3 2 0 1 2 3 3 0
Ser 7 14 2 16 14 13 7 8
Thr 3 2 14 11 7 4 5 4
Cys 0 8 0 2 0 0 0 0
Asn 3 7 0 4 2 11 16 8
Gln 9 16 0 19 5 5 9 7
Asp 10 6 0 4 8 12 25 36
Glu 7 5 0 40 29 8 12 10
Lys 0 6 0 1 8 11 3 11
Arg 3 3 0 15 1 15 5 1
His 15 1 0 3 6 2 10 3
Specificity from combinatorial peptides
 
Organism comment P4 P3 P2 P1 P1' P2' P3' P4' optimal substrate fluorophore or acceptor-donor pair Reference
Homo sapiens recombinant - K/R F/R R/G N/F R/S R/F/S/K - xKFR+NRRx Abz-EDDnp Alves et al., 2003
Homo sapiens recombinant R/H/K K/H/broad L/P/I R/K - - - - RKLR ACC Choe et al., 2006
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
CTSK 1q21 ENSG00000143387 1513 CTSK 601105
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Ctsk 3:F2.1 ENSMUSG00000028111 13038 MGI:107823