Cathepsins H (CTSH), L (CTSL), B (CTSB) and S (CTSS) are papain family cysteine
proteinases involved in a variety of physiologic processes such as proenzyme activation, enzyme inactivation, antigen
presentation, hormone maturation, tissue remodeling, and bone matrix resorption (Shi et al., 1995). In addition, cysteine
proteinases appear to be involved in a variety of pathologic processes, such as rheumatoid arthritis, glomerulonephritis,
Alzheimer disease, and cancer invasion and metastasis. All of them are glycoproteins and contain an essential cysteine
residue in their active site but differ in some enzymatic properties, including substrate specificities and pH stability.
NCBI Summary:
The protein encoded by this gene is a lysosomal cysteine proteinase involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. However, the encoded protein is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. This gene may be subject to RNA editing.
General function
Enzyme, Hydrolase, Peptidase/Protease
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Cellular localization
Secreted
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Ovarian function
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Expression regulated by
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Ovarian localization
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A 1.6-kilobase full-length cDNA of a novel human cysteine protease has been isolated and sequenced by Bromme D . The nucleotide
sequence encodes a polypeptide of 329 amino acids composed of a 15-residue N-terminal signal peptide, a 99-residue
propeptide, and a mature protein of 215 amino acids. The deduced amino acid sequence contains two potential
N-glycosylation sites, one located in the proregion and one in the mature enzyme. Comparison of the amino acid sequence of
cathepsin O2 with that of known human lysosomal cysteine proteases revealed a substantial degree of similarity to cathepsins
L and S. Northern blot analysis indicates predominant levels of expression in osteoclastomas and ovary and therefore the
enzyme was named cathepsin O2. This gene is also known as cathepsin K or CTSO2 whereas another gene cathepsin O, CTSO, has been symbolized CTSO1.
Follicle stages
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Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Lazner et al. (1999) reviewed their own work and that of others on the cathepsin K knockout mouse. Targeted mutation
of the Ctsk gene in mice resulted in many of the phenotypic features of pycnodysostosis, including increased bone
density and bone deformity. Radiographic analysis of these mice revealed that the phenotype also became progressively
pronounced with age, as does the osteopetrosis associated with pycnodysostosis. Both the human disease and the
cathepsin K knockout mouse display a bias towards abnormalities in bones that are rapidly remodeled during normal
bone development and homeostasis.
Species: human
Mutation name: None
type: naturally occurring fertility: unknown Comment:Gelb et al. (1996)
identified nonsense, missense, and stop codon mutations in the gene encoding cathepsin K in patients with pycnodysostosis.
Transient expression of complementary DNA containing the stop codon mutation resulted in mRNA but no immunologically
detectable protein. The findings suggested that cathepsin K is a major lysosomal protease in bone resorption, providing a
possible rationale for the treatment of disorders such as osteoporosis and certain forms of arthritis.