$VAR1 = undef;

Summary for peptidase C01.036: cathepsin K

Names
MEROPS Name	cathepsin K
Other names	cathepsin O [obs.], cathepsin O2 [obs.], cathepsin X [obs.], Ctsk g.p. (Homo sapiens)

Domain architecture

MEROPS Classification
Classification	Clan CA >> Subclan (none) >> Family C1 >> Subfamily A >> C01.036
Holotype	cathepsin 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 type	Cysteine
Peplist	Included in the Peplist with identifier PL00063
NC-IUBMB	Subclass 3.4 (Peptidases) >> Sub-subclass 3.4.22 (Cysteine endopeptidases) >> Peptidase 3.4.22.38
Enzymology	BRENDA database
Proteolytic events	CutDB database (11 cleavages)
Activity status	human: active (Bromme, 2004) mouse: active (Lecaille et al., 2003)
Physiology	Degrades the organic matrix of bone in osteoclastic bone resorption.
Knockout	Hereditary 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 relevance	Potential drug target for control of osteoporosis (Troen, 2004) and perhaps emphysema.
Pathways	KEGG	Lysosome
	KEGG	Osteoclast differentiation
	KEGG	Rheumatoid arthritis
	KEGG	Toll-like receptor signaling pathway
Other databases	WIKIPEDIA	http://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	-/-/l/--/-/-/- (based on 10608 cleavages)

Specificity matrix

Amino acid	P4	P3	P2	P1	P1'	P2'	P3'	P4'
Gly	692	940	128	1067	439	766	812	625
Pro	601	526	1243	15	5	439	593	694
Ala	912	901	791	1105	1067	1170	851	812
Val	697	537	1143	246	591	1009	791	726
Leu	984	699	3298	621	927	378	709	517
Ile	513	409	1284	105	582	617	522	501
Met	290	327	435	346	214	95	173	95
Phe	307	397	567	285	389	225	397	283
Tyr	248	272	118	201	324	228	326	236
Trp	102	95	18	71	34	74	56	41
Ser	648	645	399	848	750	859	596	579
Thr	492	542	304	844	476	570	422	608
Cys	180	160	189	207	85	84	91	73
Asn	344	395	54	320	444	456	593	469
Gln	577	516	215	769	525	474	480	450
Asp	366	295	37	164	614	809	901	1226
Glu	727	743	151	804	1326	1129	977	1258
Lys	919	1234	103	1429	1393	919	1023	1134
Arg	642	687	55	1019	300	136	136	100
His	228	203	74	142	111	158	146	169

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	-	xKFRNRRx	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