Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3PXIPM)

DOT Name Cathepsin S (CTSS)
Synonyms EC 3.4.22.27
Gene Name CTSS
UniProt ID
CATS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1GLO ; 1MS6 ; 1NPZ ; 1NQC ; 2C0Y ; 2F1G ; 2FQ9 ; 2FRA ; 2FRQ ; 2FT2 ; 2FUD ; 2FYE ; 2G6D ; 2G7Y ; 2H7J ; 2HH5 ; 2HHN ; 2HXZ ; 2OP3 ; 2R9M ; 2R9N ; 2R9O ; 3IEJ ; 3N3G ; 3N4C ; 3OVX ; 4P6E ; 4P6G ; 5QBU ; 5QBV ; 5QBW ; 5QBX ; 5QBY ; 5QBZ ; 5QC0 ; 5QC1 ; 5QC2 ; 5QC3 ; 5QC4 ; 5QC5 ; 5QC6 ; 5QC7 ; 5QC8 ; 5QC9 ; 5QCA ; 5QCB ; 5QCC ; 5QCD ; 5QCE ; 5QCF ; 5QCG ; 5QCH ; 5QCI ; 5QCJ ; 6YYN ; 6YYO ; 6YYP ; 6YYQ ; 6YYR
EC Number
3.4.22.27
Pfam ID
PF08246 ; PF00112
Sequence
MKRLVCVLLVCSSAVAQLHKDPTLDHHWHLWKKTYGKQYKEKNEEAVRRLIWEKNLKFVM
LHNLEHSMGMHSYDLGMNHLGDMTSEEVMSLMSSLRVPSQWQRNITYKSNPNRILPDSVD
WREKGCVTEVKYQGSCGACWAFSAVGALEAQLKLKTGKLVSLSAQNLVDCSTEKYGNKGC
NGGFMTTAFQYIIDNKGIDSDASYPYKAMDQKCQYDSKYRAATCSKYTELPYGREDVLKE
AVANKGPVSVGVDARHPSFFLYRSGVYYEPSCTQNVNHGVLVVGYGDLNGKEYWLVKNSW
GHNFGEEGYIRMARNKGNHCGIASFPSYPEI
Function
Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules and MHC class II antigen presentation. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L.
KEGG Pathway
Lysosome (hsa04142 )
Phagosome (hsa04145 )
Apoptosis (hsa04210 )
Antigen processing and presentation (hsa04612 )
Tuberculosis (hsa05152 )
Reactome Pathway
Degradation of the extracellular matrix (R-HSA-1474228 )
Trafficking and processing of endosomal TLR (R-HSA-1679131 )
Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090 )
MHC class II antigen presentation (R-HSA-2132295 )
Neutrophil degranulation (R-HSA-6798695 )
Endosomal/Vacuolar pathway (R-HSA-1236977 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
19 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Cathepsin S (CTSS). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Cathepsin S (CTSS). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Cathepsin S (CTSS). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cathepsin S (CTSS). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Cathepsin S (CTSS). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Cathepsin S (CTSS). [6]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Cathepsin S (CTSS). [7]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Cathepsin S (CTSS). [7]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Cathepsin S (CTSS). [8]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Cathepsin S (CTSS). [9]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Cathepsin S (CTSS). [10]
Bleomycin DMNER5S Approved Bleomycin increases the expression of Cathepsin S (CTSS). [7]
Valsartan DMREUQ6 Approved Valsartan decreases the expression of Cathepsin S (CTSS). [11]
OTX-015 DMI8RG1 Phase 1/2 OTX-015 decreases the expression of Cathepsin S (CTSS). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Cathepsin S (CTSS). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Cathepsin S (CTSS). [14]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Cathepsin S (CTSS). [15]
PP-242 DM2348V Investigative PP-242 decreases the expression of Cathepsin S (CTSS). [16]
methylglyoxal DMRC3OZ Investigative methylglyoxal decreases the activity of Cathepsin S (CTSS). [17]
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⏷ Show the Full List of 19 Drug(s)

References

1 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
3 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
4 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
5 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
6 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
7 Radiation-induced cathepsin S is involved in radioresistance. Int J Cancer. 2009 Apr 15;124(8):1794-801. doi: 10.1002/ijc.24095.
8 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
9 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
10 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
11 Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial. PLoS One. 2012;7(6):e39930. doi: 10.1371/journal.pone.0039930. Epub 2012 Jun 29.
12 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
13 Effect of benzo[a]pyrene on proliferation and metastasis of oral squamous cell carcinoma cells: A transcriptome analysis based on RNA-seq. Environ Toxicol. 2022 Nov;37(11):2589-2604. doi: 10.1002/tox.23621. Epub 2022 Jul 23.
14 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
15 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
16 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
17 Evidence for inactivation of cysteine proteases by reactive carbonyls via glycation of active site thiols. Biochem J. 2006 Sep 1;398(2):197-206. doi: 10.1042/BJ20060019.