Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSCX2LL)

DOT Name Cathepsin Z (CTSZ)
Synonyms EC 3.4.18.1; Cathepsin P; Cathepsin X
Gene Name CTSZ
Related Disease
Alagille syndrome ( )
Parkinson disease ( )
Acute myelogenous leukaemia ( )
Adenoma ( )
Alzheimer disease ( )
Bone giant cell tumor ( )
Breast cancer ( )
Breast carcinoma ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Malignant glioma ( )
Matthew-Wood syndrome ( )
Multiple sclerosis ( )
Myocardial infarction ( )
Neoplasm ( )
Nervous system inflammation ( )
Neuralgia ( )
Osteoporosis ( )
Primary biliary cholangitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Tuberculosis ( )
Advanced cancer ( )
Pulmonary tuberculosis ( )
Adenocarcinoma ( )
Carcinoma ( )
UniProt ID
CATZ_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
1DEU; 1EF7
EC Number
3.4.18.1
Pfam ID
PF00112
Sequence
MARRGPGWRPLLLLVLLAGAAQGGLYFRRGQTCYRPLRGDGLAPLGRSTYPRPHEYLSPA
DLPKSWDWRNVDGVNYASITRNQHIPQYCGSCWAHASTSAMADRINIKRKGAWPSTLLSV
QNVIDCGNAGSCEGGNDLSVWDYAHQHGIPDETCNNYQAKDQECDKFNQCGTCNEFKECH
AIRNYTLWRVGDYGSLSGREKMMAEIYANGPISCGIMATERLANYTGGIYAEYQDTTYIN
HVVSVAGWGISDGTEYWIVRNSWGEPWGERGWLRIVTSTYKDGKGARYNLAIEEHCTFGD
PIV
Function Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity. Capable of producing kinin potentiating peptides.
Tissue Specificity Widely expressed.
KEGG Pathway
Lysosome (hsa04142 )
Apoptosis (hsa04210 )
Reactome Pathway
COPII-mediated vesicle transport (R-HSA-204005 )
Lysosome Vesicle Biogenesis (R-HSA-432720 )
Cargo concentration in the ER (R-HSA-5694530 )
Neutrophil degranulation (R-HSA-6798695 )
Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377 )

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alagille syndrome DIS9DPU8 Definitive Altered Expression [1]
Parkinson disease DISQVHKL Definitive Altered Expression [2]
Acute myelogenous leukaemia DISCSPTN Strong Biomarker [3]
Adenoma DIS78ZEV Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Altered Expression [5]
Bone giant cell tumor DIS0RGK9 Strong Altered Expression [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [4]
Malignant glioma DISFXKOV Strong Altered Expression [8]
Matthew-Wood syndrome DISA7HR7 Strong Altered Expression [9]
Multiple sclerosis DISB2WZI Strong Biomarker [10]
Myocardial infarction DIS655KI Strong Biomarker [11]
Neoplasm DISZKGEW Strong Biomarker [4]
Nervous system inflammation DISB3X5A Strong Altered Expression [10]
Neuralgia DISWO58J Strong Biomarker [12]
Osteoporosis DISF2JE0 Strong Biomarker [13]
Primary biliary cholangitis DIS43E0O Strong Altered Expression [1]
Prostate cancer DISF190Y Strong Biomarker [14]
Prostate carcinoma DISMJPLE Strong Biomarker [14]
Tuberculosis DIS2YIMD Strong Genetic Variation [15]
Advanced cancer DISAT1Z9 moderate Biomarker [16]
Pulmonary tuberculosis DIS6FLUM moderate Genetic Variation [17]
Adenocarcinoma DIS3IHTY Limited Biomarker [18]
Carcinoma DISH9F1N Limited Biomarker [18]
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⏷ Show the Full List of 26 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Cathepsin Z (CTSZ). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Cathepsin Z (CTSZ). [27]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cathepsin Z (CTSZ). [20]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Cathepsin Z (CTSZ). [21]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Cathepsin Z (CTSZ). [22]
Ivermectin DMDBX5F Approved Ivermectin increases the expression of Cathepsin Z (CTSZ). [23]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Cathepsin Z (CTSZ). [24]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Cathepsin Z (CTSZ). [25]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Cathepsin Z (CTSZ). [26]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Cathepsin Z (CTSZ). [28]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Cathepsin Z (CTSZ). [29]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Cathepsin Z (CTSZ). [30]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Cathepsin Z (CTSZ). [31]
KOJIC ACID DMP84CS Investigative KOJIC ACID increases the expression of Cathepsin Z (CTSZ). [32]
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⏷ Show the Full List of 12 Drug(s)

References

1 Increased expression and altered localization of cathepsin Z are associated with progression to jaundice stage in primary biliary cholangitis.Sci Rep. 2018 Aug 7;8(1):11808. doi: 10.1038/s41598-018-30146-w.
2 Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson's Disease.Front Mol Neurosci. 2018 Nov 2;11:412. doi: 10.3389/fnmol.2018.00412. eCollection 2018.
3 Discovery of epigenetically silenced genes in acute myeloid leukemias.Leukemia. 2007 May;21(5):1026-34. doi: 10.1038/sj.leu.2404611. Epub 2007 Mar 1.
4 Characterization of cathepsin X in colorectal cancer development and progression.Pathol Res Pract. 2014 Dec;210(12):822-9. doi: 10.1016/j.prp.2014.08.014. Epub 2014 Sep 18.
5 Diverse Protein Profiles in CNS Myeloid Cells and CNS Tissue From Lipopolysaccharide- and Vehicle-Injected APP(SWE)/PS1(E9) Transgenic Mice Implicate Cathepsin Z in Alzheimer's Disease.Front Cell Neurosci. 2018 Nov 6;12:397. doi: 10.3389/fncel.2018.00397. eCollection 2018.
6 Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas.J Bone Miner Res. 1995 Aug;10(8):1197-202. doi: 10.1002/jbmr.5650100809.
7 Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice.Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2497-502. doi: 10.1073/pnas.0907240107. Epub 2010 Jan 21.
8 Localization patterns of cathepsins K and X and their predictive value in glioblastoma.Radiol Oncol. 2018 Oct 18;52(4):433-442. doi: 10.2478/raon-2018-0040.
9 S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells.Am J Pathol. 2012 Apr;180(4):1485-94. doi: 10.1016/j.ajpath.2011.12.031. Epub 2012 Feb 11.
10 A role for cathepsin Z in neuroinflammation provides mechanistic support for an epigenetic risk factor in multiple sclerosis.J Neuroinflammation. 2017 May 10;14(1):103. doi: 10.1186/s12974-017-0874-x.
11 Differential urinary proteomics analysis of myocardial infarction using iTRAQ quantification.Mol Med Rep. 2019 May;19(5):3972-3988. doi: 10.3892/mmr.2019.10088. Epub 2019 Mar 26.
12 Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model.BMC Neurosci. 2008 Aug 12;9:80. doi: 10.1186/1471-2202-9-80.
13 Cathepsin Z as a novel potential biomarker for osteoporosis.Sci Rep. 2019 Jul 5;9(1):9752. doi: 10.1038/s41598-019-46068-0.
14 Tissue Proteome Signatures Associated with Five Grades of Prostate Cancer and Benign Prostatic Hyperplasia.Proteomics. 2019 Nov;19(21-22):e1900174. doi: 10.1002/pmic.201900174. Epub 2019 Oct 20.
15 Polymorphisms in MC3R promoter and CTSZ 3'UTR are associated with tuberculosis susceptibility.Eur J Hum Genet. 2011 Jun;19(6):676-81. doi: 10.1038/ejhg.2011.1. Epub 2011 Feb 2.
16 Identification and characterization of the novel reversible and selective cathepsin X inhibitors.Sci Rep. 2017 Sep 13;7(1):11459. doi: 10.1038/s41598-017-11935-1.
17 Association of CTSZ rs34069356 and MC3R rs6127698 gene polymorphisms with pulmonary tuberculosis.Int J Tuberc Lung Dis. 2013 Sep;17(9):1224-8. doi: 10.5588/ijtld.12.0762. Epub 2013 Jul 3.
18 Up-regulation of cathepsin X in prostate cancer and prostatic intraepithelial neoplasia.Prostate. 2004 Jul 1;60(2):109-19. doi: 10.1002/pros.20046.
19 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.
20 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.
21 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
22 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.
23 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
24 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
25 A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med. 2006 Dec;3(12):e486. doi: 10.1371/journal.pmed.0030486.
26 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
27 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
28 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
29 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
30 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
31 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
32 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.