Primary Information
BoMiProt ID	Bomi14
Protein Name	Cathepsin S
Organism	Bos taurus
Uniprot ID	P25326
Milk Fraction	Whey
Ref Sequence ID	NP_001028787.1
Aminoacid Length	331
Molecular Weight	37176
FASTA Sequence	Download
Gene Name	CTSS
Gene ID	327711
Protein Existence Status	Reviewed: Experimental evidence at protein level
Secondary Information
Presence in other biological fluids/tissue/cells	Serum, synovial fluid, lymph nodes, spleen
Protein Function	Plays several roles in the disease process of RA; stable at physiological pH and is involved in the major histocompatibility complex class II (MHC II)-mediated antigen presentation, degradation of the extracellular matrix in atherosclerosis, and other inflammatory diseases as well as in tumor progression;
Biochemical Properties	cathepsin S has the property of degrading proteins and peptides not only at acid but also at neutral pH values; pH optimum of cathepsin S is at pH 6.5, and about 60 70% of activity is retained after 1 h at pH 7.5; shows collagenolytic and elastinolytic activities; Endogenous inhibitors are α2-macroglobulin, cystatins, chloromethanes, fluoromethanes, O-acylhydroxylamines, and vinyl sulfones
PTMs	potential glycosylation sites are located in the propeptide at position Asn104 in the human enzyme; Asn100 as well as Asn110 in the rat enzyme; Human cathepsin S contains three disulfide bonds (Cys136-Cys180, Cys170-Cys213, Cys272-Cys320). Cys139, His278 and Asn298
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation
Predicted Disorder Regions	NA
DisProt Annotation
TM Helix Prediction	No TM helices
Significance of PTMs	Disulfide bonds are directed towards catalytic activity
Additional Comments	Cathepsin S is an endopeptidase with no detected exopeptidase activities. The substrate specificity is similar to that of cathepsins B, K, and L;
Bibliography	1. Weitoft, T., Larsson, A., Manivel, V. A., Lysholm, J., Knight, A., & Rönnelid, J. (2015). Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies. Rheumatology (Oxford, England), 54(10), 1923–1928. https://doi.org/10.1093/rheumatology/keu486. 2. Wiederanders, B., Brömme, D., Kirschke, H., von Figura, K., Schmidt, B., & Peters, C. (1992). Phylogenetic conservation of cysteine proteinases. Cloning and expression of a cDNA coding for human cathepsin S. The Journal of Biological Chemistry, 267(19), 13708–13713. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1377692. 3. Shi, G. P., Munger, J. S., Meara, J. P., Rich, D. H., & Chapman, H. A. (1992). Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. The Journal of Biological Chemistry, 267(11), 7258–7262. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1373132. 4. Brömme, D., & Demuth, H. U. (1994). N,O-diacyl hydroxamates as selective and irreversible inhibitors of cysteine proteinases. Methods in Enzymology, 244, 671–685. https://doi.org/10.1016/0076-6879(94)44050-6. 5. Turk, B., Colić, A., Stoka, V., & Turk, V. (1994). Kinetics of inhibition of bovine cathepsin S by bovine stefin B. FEBS Letters, 339(1–2), 155–159. https://doi.org/10.1016/0014-5793(94)80405-2. 6. Kirschke, H., Wiederanders, B., Brömme, D., & Rinne, A. (1989). Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. The Biochemical Journal, 264(2), 467–473. https://doi.org/10.1042/bj2640467. 7. Xin, X. Q., Gunesekera, B., & Mason, R. W. (1992). The specificity and elastinolytic activities of bovine cathepsins S and H. Archives of Biochemistry and Biophysics, 299(2), 334–339. https://doi.org/10.1016/0003-9861(92)90283-3. 8. Turnsek, T., Kregar, I., & Lebez, D. (1975). Acid sulphydryl protease from calf lymph nodes. Biochimica et Biophysica Acta, 403(2), 514–520. https://doi.org/10.1016/0005-2744(75)90079-0.