Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2AX2QL)

• DOT Name: Secretion-regulating guanine nucleotide exchange factor (SERGEF)
• Synonyms: Deafness locus-associated putative guanine nucleotide exchange factor; DelGEF; Guanine nucleotide exchange factor-related protein
• Gene Name: SERGEF
• Related Disease:
  Stroke
  Sensorineural hearing loss disorder
• UniProt ID: SRGEF_HUMAN
• Pfam ID: PF00415 ; PF13540
• Sequence:
  MEREPSASEAAPAAAALFAWGANSYGQLGLGHKEDVLLPQQLNDFCKPRSVRRITGGGGH
  SAVVTDGGDLFVCGLNKDGQLGLGHTEDIPYFTPCKSLFGCPIQQVACGWDFTIMLTENG
  QVLSCGSNSFGQLGVPHGPRRCVVPQAIELHKEKVVCIAAGLRHAVAATASGIVFQWGTG
  LASCGRRLCPGQTLPLFFTAKEPSRVTGLENSKAMCVLAGSDHSASLTDAGEVYVWGSNK
  HGQLANEAAFLPVPQKIEAHCFQNEKVTAIWSGWTHLVAQTETGKMFTWGRADYGQLGRK
  LETYEGWKLEKQDSFLPCSRPPNSMPSSPHCLTGATEVSCGSEHNLAIIGGVCYSWGWNE
  HGMCGDGTEANVWAPKPVQALLSSSGLLVGCGAGHSLALCQLPAHPALVQDPKVTYLSPD
  AIEDTESQKAMDKERNWKERQSETSTQSQSDWSRNGGL
• Function: Probable guanine nucleotide exchange factor (GEF), which may be involved in the secretion process.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Stroke	DISX6UHX	Definitive	Genetic Variation	[1]
Sensorineural hearing loss disorder	DISJV45Z	moderate	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Secretion-regulating guanine nucleotide exchange factor (SERGEF).	[16]

References

• [1] Admixture Mapping of Subclinical Atherosclerosis and Subsequent Clinical Events Among African Americans in 2 Large Cohort Studies.Circ Cardiovasc Genet. 2017 Apr;10(2):e001569. doi: 10.1161/CIRCGENETICS.116.001569.
• [2] DelGEF, an RCC1-related protein encoded by a gene on chromosome 11p14 critical for two forms of hereditary deafness.FEBS Lett. 1999 Oct 22;460(1):153-60. doi: 10.1016/s0014-5793(99)01333-2.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [11] 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.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] 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.
• [14] 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.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.