Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3CPI8L)

• DOT Name: Gamma-synuclein (SNCG)
• Synonyms: Breast cancer-specific gene 1 protein; Persyn; Synoretin; SR
• Gene Name: SNCG
• UniProt ID: SYUG_HUMAN
• Pfam ID: PF01387
• Sequence:
  MDVFKKGFSIAKEGVVGAVEKTKQGVTEAAEKTKEGVMYVGAKTKENVVQSVTSVAEKTK
  EQANAVSEAVVSSVNTVATKTVEEAENIAVTSGVVRKEDLRPSAPQQEGEASKEKEEVAE
  EAQSGGD
• Function: Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to calcium-dependent proteases. May also function in modulating the keratin network in skin. Activates the MAPK and Elk-1 signal transduction pathway.
• Tissue Specificity: Highly expressed in brain, particularly in the substantia nigra. Also expressed in the corpus callosum, heart, skeletal muscle, ovary, testis, colon and spleen. Weak expression in pancreas, kidney and lung.

Molecular Interaction Atlas (MIA) 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 Gamma-synuclein (SNCG).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gamma-synuclein (SNCG).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Gamma-synuclein (SNCG).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Gamma-synuclein (SNCG).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Gamma-synuclein (SNCG).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Gamma-synuclein (SNCG).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Gamma-synuclein (SNCG).	[6]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Gamma-synuclein (SNCG).	[7]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Gamma-synuclein (SNCG).	[8]

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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [5] 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.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [8] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.