1. Gene Aliases

Cathepsin K, CTSO2, PKND, CTSO, Cathepsin O2, EC 3.4.22.38, Cathepsin O, Cathepsin X, PYCD, Cathepsin K (Pycnodysostosis), Cathepsin O1, EC 3.4.22, CTS02, CTSO1 [https://www.genecards.org/cgi-bin/carddisp.pl?gene=CTSK&keywords=Ctsk]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

apoptotic process [A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. GO:0006915]

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. GO:0045453]

cellular response to transforming growth factor beta stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus. GO:0071560]

cellular response to tumor necrosis factor [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus. GO:0071356]

cellular response to zinc ion starvation [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of zinc ions. GO:0034224]

collagen catabolic process [The proteolytic chemical reactions and pathways resulting in the breakdown of collagen in the extracellular matrix, usually carried out by proteases secreted by nearby cells. GO:0030574]

immune response [Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. GO:0006955]

intramembranous ossification [Direct ossification that occurs within mesenchyme or an accumulation of relatively unspecialized cells.|An instance of intramembranous ossification may also be classified as metaplastic; the former classifies based on tissue type location, and the latter based on mechanism/cell division. GO:0001957]

mononuclear cell differentiation [The process in which a relatively unspecialized cell acquires the specialized features of a mononuclear cell. GO:1903131]

negative regulation of cartilage development [Any process that decreases the rate, frequency, or extent of cartilage development, the process whose specific outcome is the progression of the cartilage over time, from its formation to the mature structure. Cartilage is a connective tissue dominated by extracellular matrix containing collagen type II and large amounts of proteoglycan, particularly chondroitin sulfate. GO:0061037]

positive regulation of apoptotic signaling pathway [Any process that activates or increases the frequency, rate or extent of apoptotic signaling pathway. GO:2001235]

proteolysis [The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds.|This term was intentionally placed under 'protein metabolic process ; GO:0019538' rather than 'protein catabolic process ; GO:0030163' to cover all processes centered on breaking peptide bonds, including those involved in protein processing. GO:0006508]

proteolysis involved in protein catabolic process [The hydrolysis of a peptide bond or bonds within a protein as part of the chemical reactions and pathways resulting in the breakdown of a protein by individual cells. GO:0051603]

response to ethanol [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus. GO:0045471]

response to insulin [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms. GO:0032868]

response to organic cyclic compound [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus. GO:0014070]

thyroid hormone generation [The formation of either of the compounds secreted by the thyroid gland, mainly thyroxine and triiodothyronine. This is achieved by the iodination and joining of tyrosine molecules to form the precursor thyroglobin, proteolysis of this precursor gives rise to the thyroid hormones.|Note that this term does not fall under the general GO definition for biosynthetic processes, which is 'The chemical reactions and pathways resulting in the formation of... ', because thyroid hormones can only be formed by the proteolysis of a larger molecule (see term definition). The word 'generation' is therefore used in place of biosynthesis. GO:0006590]

MSigDB Signatures:

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

REACTOME_ADAPTIVE_IMMUNE_SYSTEM: Adaptive Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ADAPTIVE_IMMUNE_SYSTEM.html]

KEGG_LYSOSOME: Lysosome [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_LYSOSOME.html]

REACTOME_COLLAGEN_DEGRADATION: Collagen degradation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_COLLAGEN_DEGRADATION.html]

REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION: Extracellular matrix organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_EXTRACELLULAR_MATRIX_ORGANIZATION.html]

REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX: Degradation of the extracellular matrix [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEGRADATION_OF_THE_EXTRACELLULAR_MATRIX.html]

NABA_MATRISOME_ASSOCIATED: Ensemble of genes encoding ECM-associated proteins including ECM-affilaited proteins, ECM regulators and secreted factors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME_ASSOCIATED.html]

REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX1: Transcriptional regulation by RUNX1 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_TRANSCRIPTIONAL_REGULATION_BY_RUNX1.html]

NABA_MATRISOME: Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME.html]

WP_OSTEOCLAST_SIGNALING: Osteoclast signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_OSTEOCLAST_SIGNALING.html]

REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION: RNA Polymerase II Transcription [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION.html]

REACTOME_ACTIVATION_OF_MATRIX_METALLOPROTEINASES: Activation of Matrix Metalloproteinases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ACTIVATION_OF_MATRIX_METALLOPROTEINASES.html]

WP_IL_26_SIGNALING_PATHWAYS: IL 26 signaling pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_IL_26_SIGNALING_PATHWAYS.html]

CARRILLOREIXACH_MRS3_VS_LOWER_RISK_HEPATOBLASTOMA_DN: Genes significantly down-regulated in the high-risk Molecular Risk Stratification (MRS-3) hepatoblastoma (HB) as compared with intermediate-risk (MRS-2) and low-risk (MRS-1) molecular HBs, assessed by Human Transcriptome Array (HTA). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CARRILLOREIXACH_MRS3_VS_LOWER_RISK_HEPATOBLASTOMA_DN.html]

REACTOME_RUNX1_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_DIFFERENTIATION_OF_KERATINOCYTES: RUNX1 regulates transcription of genes involved in differentiation of keratinocytes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_RUNX1_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_DIFFERENTIATION_OF_KERATINOCYTES.html]

KEGG_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY: Toll-like receptor signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY.html]

REACTOME_MHC_CLASS_II_ANTIGEN_PRESENTATION: MHC class II antigen presentation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_MHC_CLASS_II_ANTIGEN_PRESENTATION.html]

7. Gene Descriptions

NCBI Gene 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. [provided by RefSeq, Apr 2013]

GeneCards Summary: CTSK (Cathepsin K) is a Protein Coding gene. Diseases associated with CTSK include Pycnodysostosis and Nail Disorder, Nonsyndromic Congenital, 9. Among its related pathways are Gene expression (Transcription) and Innate Immune System. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and collagen binding. An important paralog of this gene is CTSS.

UniProtKB/Swiss-Prot Summary: Thiol protease 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. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen [PMID: 11082042].

8. Cellular Location of Gene Product

Mainly localized to vesicles. Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000143387/subcellular]

9. Mechanistic Information

Summary

Ctsk, encoding Cathepsin K, is dysregulated in lung diseases and toxicities due to its role in extracellular matrix degradation and response to inflammation [CS: 8]. In lung fibrosis, a condition characterized by excessive collagen deposition and fibrous tissue formation, the overexpression of Ctsk and increased Cathepsin K protein expression are observed [CS: 7]. This elevation in Ctsk activity aids in breaking down excessive collagen, as Cathepsin K can degrade collagen, particularly under acidic conditions [CS: 9].

Inflammatory conditions in the lung, like those induced by toxic exposures, often result in elevated levels of cytokines such as TNFalpha and IL-1beta [CS: 8]. These cytokines, in turn, increase the expression of Ctsk in various cells, including lung fibroblasts [CS: 7]. The upregulation of Ctsk under these conditions might serve to counteract the effects of inflammation and excessive extracellular matrix deposition [CS: 6]. For example, in pulmonary fibrosis induced by agents like bleomycin, overexpression of cathepsin K has been shown to reduce lung collagen deposition and improve lung function, suggesting a compensatory mechanism to maintain lung matrix homeostasis and function amid toxic stress [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: cervix (tissue enhanced) [https://www.proteinatlas.org/ENSG00000143387/tissue]

Cell type enchanced: fibroblasts, langerhans cells, leydig cells, peritubular cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000143387/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: