General Information of Drug Off-Target (DOT) (ID: OTCIZU2A)

DOT Name Complement C1s subcomponent (C1S)
Synonyms EC 3.4.21.42; C1 esterase; Complement component 1 subcomponent s
Gene Name C1S
Related Disease
Complement component C1s deficiency ( )
Ehlers-Danlos syndrome, periodontal type 2 ( )
Ehlers-Danlos syndrome, periodontal type 1 ( )
Ehlers-Danlos syndrome, periodontitis type ( )
UniProt ID
C1S_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1ELV; 1NZI; 4J1Y; 4LMF; 4LOR; 4LOS; 4LOT; 6F1C; 6F1H; 8GMN; 8TYP
EC Number
3.4.21.42
Pfam ID
PF00431 ; PF14670 ; PF00084 ; PF00089
Sequence
MWCIVLFSLLAWVYAEPTMYGEILSPNYPQAYPSEVEKSWDIEVPEGYGIHLYFTHLDIE
LSENCAYDSVQIISGDTEEGRLCGQRSSNNPHSPIVEEFQVPYNKLQVIFKSDFSNEERF
TGFAAYYVATDINECTDFVDVPCSHFCNNFIGGYFCSCPPEYFLHDDMKNCGVNCSGDVF
TALIGEIASPNYPKPYPENSRCEYQIRLEKGFQVVVTLRREDFDVEAADSAGNCLDSLVF
VAGDRQFGPYCGHGFPGPLNIETKSNALDIIFQTDLTGQKKGWKLRYHGDPMPCPKEDTP
NSVWEPAKAKYVFRDVVQITCLDGFEVVEGRVGATSFYSTCQSNGKWSNSKLKCQPVDCG
IPESIENGKVEDPESTLFGSVIRYTCEEPYYYMENGGGGEYHCAGNGSWVNEVLGPELPK
CVPVCGVPREPFEEKQRIIGGSDADIKNFPWQVFFDNPWAGGALINEYWVLTAAHVVEGN
REPTMYVGSTSVQTSRLAKSKMLTPEHVFIHPGWKLLEVPEGRTNFDNDIALVRLKDPVK
MGPTVSPICLPGTSSDYNLMDGDLGLISGWGRTEKRDRAVRLKAARLPVAPLRKCKEVKV
EKPTADAEAYVFTPNMICAGGEKGMDSCKGDSGGAFAVQDPNDKTKFYAAGLVSWGPQCG
TYGLYTRVKNYVDWIMKTMQENSTPRED
Function
C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
KEGG Pathway
Complement and coagulation cascades (hsa04610 )
Pertussis (hsa05133 )
Staphylococcus aureus infection (hsa05150 )
Coro.virus disease - COVID-19 (hsa05171 )
Systemic lupus erythematosus (hsa05322 )
Reactome Pathway
Classical antibody-mediated complement activation (R-HSA-173623 )
Regulation of Complement cascade (R-HSA-977606 )
Initial triggering of complement (R-HSA-166663 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Complement component C1s deficiency DISART3A Strong Autosomal recessive [1]
Ehlers-Danlos syndrome, periodontal type 2 DISP04IM Strong Autosomal dominant [2]
Ehlers-Danlos syndrome, periodontal type 1 DIS4VQMI Moderate Autosomal dominant [3]
Ehlers-Danlos syndrome, periodontitis type DISB3QMD Supportive Autosomal dominant [4]
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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 Complement C1s subcomponent (C1S). [5]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Complement C1s subcomponent (C1S). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Complement C1s subcomponent (C1S). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Complement C1s subcomponent (C1S). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Complement C1s subcomponent (C1S). [9]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Complement C1s subcomponent (C1S). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Complement C1s subcomponent (C1S). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Complement C1s subcomponent (C1S). [13]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Complement C1s subcomponent (C1S). [14]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Complement C1s subcomponent (C1S). [15]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Complement C1s subcomponent (C1S). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Complement C1s subcomponent (C1S). [17]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Complement C1s subcomponent (C1S). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Complement C1s subcomponent (C1S). [6]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Complement C1s subcomponent (C1S). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Complement C1s subcomponent (C1S). [20]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Complement C1s subcomponent (C1S). [21]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Complement C1s subcomponent (C1S). [22]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Complement C1s subcomponent (C1S). [23]
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⏷ Show the Full List of 19 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Complement C1s subcomponent (C1S). [12]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
D-glucose DMMG2TO Investigative D-glucose affects the secretion of Complement C1s subcomponent (C1S). [24]
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References

1 Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases. J Immunol. 2001 Jun 15;166(12):7612-6. doi: 10.4049/jimmunol.166.12.7612.
2 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
3 Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. J Am Coll Cardiol. 2018 Aug 7;72(6):605-615. doi: 10.1016/j.jacc.2018.04.089.
4 Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement. Am J Hum Genet. 2016 Nov 3;99(5):1005-1014. doi: 10.1016/j.ajhg.2016.08.019. Epub 2016 Oct 13.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
7 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
8 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.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
11 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
12 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
13 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
16 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
17 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
18 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
19 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.
20 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
21 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
22 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
23 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.
24 Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim Biophys Acta. 2014 Sep;1844(9):1511-22. doi: 10.1016/j.bbapap.2014.04.023. Epub 2014 May 5.