Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFI2BQX)

• DOT Name: Androgen-dependent TFPI-regulating protein (ADTRP)
• Synonyms: Fatty acid esters of hydroxy fatty acids hydrolase ADTRP; FAHFA hydrolase ADTRP; EC 3.1.-.-
• Gene Name: ADTRP
• Related Disease:
  Cardiovascular disease
  Coronary atherosclerosis
  Coronary heart disease
  Isolated cleft lip
  Myocardial infarction
  Arteriosclerosis
  Atherosclerosis
• UniProt ID: ADTRP_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF04750
• Sequence:
  MTKTSTCIYHFLVLSWYTFLNYYISQEGKDEVKPKILANGARWKYMTLLNLLLQTIFYGV
  TCLDDVLKRTKGGKDIKFLTAFRDLLFTTLAFPVSTFVFLAFWILFLYNRDLIYPKVLDT
  VIPVWLNHAMHTFIFPITLAEVVLRPHSYPSKKTGLTLLAAASIAYISRILWLYFETGTW
  VYPVFAKLSLLGLAAFFSLSYVFIASIYLLGEKLNHWKWGDMRQPRKKRK
• Function: Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids. Show a preference for FAHFAs with branching distal from the carboxylate head group of the lipids. Regulates the expression and the cell-associated anticoagulant activity of the inhibitor TFPI in endothelial cells (in vitro).
• Tissue Specificity: Expressed in cultured endothelial cells and in placenta.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[2]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[2]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[3]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[1]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[2]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[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 Androgen-dependent TFPI-regulating protein (ADTRP).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Androgen-dependent TFPI-regulating protein (ADTRP).	[9]

6 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 Androgen-dependent TFPI-regulating protein (ADTRP).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Androgen-dependent TFPI-regulating protein (ADTRP).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Androgen-dependent TFPI-regulating protein (ADTRP).	[7]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Androgen-dependent TFPI-regulating protein (ADTRP).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Androgen-dependent TFPI-regulating protein (ADTRP).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Androgen-dependent TFPI-regulating protein (ADTRP).	[11]

References

• [1] Androgen inhibits key atherosclerotic processes by directly activating ADTRP transcription.Biochim Biophys Acta Mol Basis Dis. 2017 Sep;1863(9):2319-2332. doi: 10.1016/j.bbadis.2017.06.015. Epub 2017 Jun 20.
• [2] Identification of a molecular signaling gene-gene regulatory network between GWAS susceptibility genes ADTRP and MIA3/TANGO1 for coronary artery disease.Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1640-1653. doi: 10.1016/j.bbadis.2017.03.010. Epub 2017 Mar 21.
• [3] Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate.Genet Epidemiol. 2011 Sep;35(6):469-78. doi: 10.1002/gepi.20595. Epub 2011 May 26.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [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] 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.
• [11] 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.