Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHKQ4K4)

• DOT Name: Inactive ADP-ribosyltransferase ARH2 (ADPRHL1)
• Synonyms: ADP-ribosylhydrolase-like protein 1; hydrolase-like protein 1
• Gene Name: ADPRHL1
• Related Disease: Uveal Melanoma
• UniProt ID: ARHL1_HUMAN
• Pfam ID: PF03747
• Sequence:
  MEKFKAAMLLGSVGDALGYRNVCKENSTVGMKIQEELQRSGGLDHLVLSPGEWPVSDNTI
  MHIATAEALTTDYWCLDDLYREMVRCYVEIVEKLPERRPDPATIEGCAQLKPNNYLLAWH
  TPFNEKGSGFGAATKAMCIGLRYWKPERLETLIEVSVECGRMTHNHPTGFLGSLCTALFV
  SFAAQGKPLVQWGRDMLRAVPLAEEYCRKTIRHTAEYQEHWFYFEAKWQFYLEERKISKD
  SENKAIFPDNYDAEEREKTYRKWSSEGRGGRRGHDAPMIAYDALLAAGNSWTELCHRAMF
  HGGESAATGTIAGCLFGLLYGLDLVPKGLYQDLEDKEKLEDLGAALYRLSTEEK
• Function: Required for myofibril assembly and outgrowth of the cardiac chambers in the developing heart. Appears to be catalytically inactive, showing no activity against O-acetyl-ADP-ribose.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[1]

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 Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Inactive ADP-ribosyltransferase ARH2 (ADPRHL1).	[9]

References

• [1] Co-expression modules construction by WGCNA and identify potential prognostic markers of uveal melanoma.Exp Eye Res. 2018 Jan;166:13-20. doi: 10.1016/j.exer.2017.10.007. Epub 2017 Oct 12.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] 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.
• [8] 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.
• [9] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.