Closely 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.
Catalysis of the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile.
Cathepsin K is a recently identified lysosomal cysteine proteinase that is the major protease responsible for bone resorption and remodeling. Mutations in this gene cause the sclerosing osteochondrodysplasia pycnodysostosis. To assess its evolutionary relatedness to other cysteine proteases and to facilitate mutation identification in patients with pycnodysostosis, a genomic clone, 74e16, containing the cathepsin K gene was isolated from a human PAC library, and the cathepsin K genomic structure was determined. The cathepsin K gene contained eight exons and spanned approximately 9 kb. The transcription initiation site, determined by primer extension analysis, was 169 nucleotides upstream from the translation initiation site. The 5'-flanking region lacked a TATA box but contained two AP1 sites. Comparison of genomic and cDNA sequences suggested that this flanking sequence may be the major promoter in osteoclasts and macrophages. Cathepsin K was mapped to chromosome 1q21 by fluorescence in situ hybridization and found to reside within 150 kb of an evolutionarily related cysteine protease, cathepsin S. These findings expand our understanding of the papain family lysosomal cysteine proteases and should facilitate mutation analysis in pycnodysostosis.
Catalysis of the hydrolysis of peptide bonds in a polypeptide chain by a mechanism in which the sulfhydryl group of a cysteine residue at the active center acts as a nucleophile.
We have previously cloned a rabbit cDNA clone (OC-2) from an osteoclast cDNA library by the differential screening. OC-2 was found to encode a novel cysteine proteinase, tentatively called cathepsin K, which is predominantly expressed in osteoclasts. By use of a rabbit OC-2 fragment as a probe, its human counterpart was cloned from a cDNA library of osteoarthritic hip bone. The cloned human cDNA (hOC-2) encoded a protein of 329 amino acid residues and its deduced amino acid sequence showed 94% homology to rabbit cathepsin K. Multiple alignment of amino acid sequences of human cathepsins B, H, L, S and K showed the highest homology of cathepsin K to cathepsin S 48%. Northern blot analysis showed that cathepsin K mRNA is expressed at high levels in some osteoarthritic hip bones and at a very high level in osteoclastoma compared to very low levels in other tissues. These results suggest that cathepsin K is closely involved in human osteoclastic bone resorption.
The process in which specialized cells known as osteoclasts degrade the organic and inorganic portions of bone, and endocytose and transport the degradation products.
The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds.
IEAUniProtKB KW
Enzymatic activity
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.22.38: Broad proteolytic activity. With small-molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.
Enzyme which catalyzes hydrolysis reaction, i.e. the addition of the hydrogen and hydroxyl ions of water to a molecule with its consequent splitting into two or more simpler molecules.
Proteolytic enzyme with a cysteine residue (Cys) in its active site. There are many families of thiol proteases. The most well known one is the papain family (C1 in MEROPS classification) which is known to exist in most eukaryotes.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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