Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene. [5] [6]
Cathepsin K, abbreviated CTSK, is an enzyme that in humans is encoded by the CTSK gene. [5] [6]
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.
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.
An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium.
Cathepsins are proteases found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. Cathepsins have a vital role in mammalian cellular turnover.
Cathepsin S is a protein that in humans is encoded by the CTSS gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene.
Cathepsin O is an enzyme that in humans is encoded by the CTSO gene.
Tartrate-resistant acid phosphatase, also called acid phosphatase 5, tartrate resistant (ACP5), is a glycosylated monomeric metalloprotein enzyme expressed in mammals. It has a molecular weight of approximately 35kDa, a basic isoelectric point (7.6–9.5), and optimal activity in acidic conditions. TRAP is synthesized as latent proenzyme and activated by proteolytic cleavage and reduction. It is differentiated from other mammalian acid phosphatases by its resistance to inhibition by tartrate and by its molecular weight.
Cathepsin B belongs to a family of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis. In humans, cathepsin B is encoded by the CTSB gene. Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.
Cathepsin L1 is a protein that in humans is encoded by the CTSL1 gene. The protein is a cysteine cathepsin, a lysosomal cysteine protease that plays a major role in intracellular protein catabolism.
Cystatin-A is a protein that in humans is encoded by the CSTA gene.
Cathepsin H is a protein that in humans is encoded by the CTSH gene.
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the SPINK5 gene.
Cystatin-SN is a protein that in humans is encoded by the CST1 gene.
Transmembrane protease, serine 2 is an enzyme that in humans is encoded by the TMPRSS2 gene. It belongs to the TMPRSS family of proteins, whose members are transmembrane proteins which have a serine protease activity. The TMPRSS2 protein is found in high concentration in the cell membranes of epithelial cells of the lung and of the prostate, but also in the heart, liver and gastrointestinal tract.
Cystatin-SA is a protein that in humans is encoded by the CST2 gene.
Legumain is a protein that in humans is encoded by the LGMN gene.
Cathepsin L2 is a protein encoded in humans by the CTSV gene.
Cathepsin W is a protein that in humans is encoded by the CTSW gene.
Serpin B13 is a protein that in humans is encoded by the SERPINB13 gene.
Cathepsin F is a protein that in humans is encoded by the CTSF gene.
Pycnodysostosis, is a lysosomal storage disease of the bone caused by a mutation in the gene that codes the enzyme cathepsin K. It is also known as PKND and PYCD.
Papain-like proteases are a large protein family of cysteine protease enzymes that share structural and enzymatic properties with the group's namesake member, papain. They are found in all domains of life. In animals, the group is often known as cysteine cathepsins or, in older literature, lysosomal peptidases. In the MEROPS protease enzyme classification system, papain-like proteases form Clan CA. Papain-like proteases share a common catalytic dyad active site featuring a cysteine amino acid residue that acts as a nucleophile.
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