Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTVS1LN)

• DOT Name: Protein SYS1 homolog (SYS1)
• Gene Name: SYS1
• Related Disease:
  Autoimmune disease
  Stroke
  Systemic sclerosis
• UniProt ID: SYS1_HUMAN
• Pfam ID: PF09801
• Sequence:
  MAGQFRSYVWDPLLILSQIVLMQTVYYGSLGLWLALVDGLVRSSPSLDQMFDAEILGFST
  PPGRLSMMSFILNALTCALGLLYFIRRGKQCLDFTVTVHFFHLLGCWFYSSRFPSALTWW
  LVQAVCIALMAVIGEYLCMRTELKEIPLNSAPKSNV
• Function: Involved in protein trafficking. May serve as a receptor for ARFRP1.
• Reactome Pathway: Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Altered Expression	[1]
Stroke	DISX6UHX	Strong	Biomarker	[2]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[3]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein SYS1 homolog (SYS1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein SYS1 homolog (SYS1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein SYS1 homolog (SYS1).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein SYS1 homolog (SYS1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein SYS1 homolog (SYS1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein SYS1 homolog (SYS1).	[10]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein SYS1 homolog (SYS1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein SYS1 homolog (SYS1).	[11]

References

• [1] Genetic risk variants for autoimmune diseases that influence gene expression in thymus.Hum Mol Genet. 2016 Jul 15;25(14):3117-3124. doi: 10.1093/hmg/ddw152. Epub 2016 May 19.
• [2] A new method for correcting middle cerebral artery flow velocity for age by calculating Z-scores.J Neurosci Methods. 2018 Sep 1;307:1-7. doi: 10.1016/j.jneumeth.2018.06.009. Epub 2018 Jun 18.
• [3] Expression of apoptotic and proliferation factors in gastric mucosa of patients with systemic sclerosis correlates with form of the disease.Sci Rep. 2019 Dec 5;9(1):18461. doi: 10.1038/s41598-019-54988-0.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.