Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8L5J3C)

• DOT Name: HIRA-interacting protein 3 (HIRIP3)
• Gene Name: HIRIP3
• UniProt ID: HIRP3_HUMAN
• Pfam ID: PF09649
• Sequence:
  MAREKEMQEFTRSFFRGRPDLSTLTHSIVRRRYLAHSGRSHLEPEEKQALKRLVEEELLK
  MQVDEAASREDKLDLTKKGKRPPTPCSDPERKRFRFNSESESGSEASSPDYFGPPAKNGV
  AAEVSPAKEENPRRASKAVEESSDEERQRDLPAQRGEESSEEEEKGYKGKTRKKPVVKKQ
  APGKASVSRKQAREESEESEAEPVQRTAKKVEGNKGTKSLKESEQESEEEILAQKKEQRE
  EEVEEEEKEEDEEKGDWKPRTRSNGRRKSAREERSCKQKSQAKRLLGDSDSEEEQKEAAS
  SGDDSGRDREPPVQRKSEDRTQLKGGKRLSGSSEDEEDSGKGEPTAKGSRKMARLGSTSG
  EESDLEREVSDSEAGGGPQGERKNRSSKKSSRKGRTRSSSSSSDGSPEAKGGKAGSGRRG
  EDHPAVMRLKRYIRACGAHRNYKKLLGSCCSHKERLSILRAELEALGMKGTPSLGKCRAL
  KEQREEAAEVASLDVANIISGSGRPRRRTAWNPLGEAAPPGELYRRTLDSDEERPRPAPP
  DWSHMRGIISSDGESN
• Function: May play a role in chromatin function and histone metabolism via its interaction with HIRA and histones.
• Tissue Specificity: Widely expressed. Isoform 1 is predominant in skeletal muscle. Isoform 2 is predominant in liver and heart.

Molecular Interaction Atlas (MIA) of This DOT

4 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 HIRA-interacting protein 3 (HIRIP3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of HIRA-interacting protein 3 (HIRIP3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of HIRA-interacting protein 3 (HIRIP3).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of HIRA-interacting protein 3 (HIRIP3).	[9]

10 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 HIRA-interacting protein 3 (HIRIP3).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of HIRA-interacting protein 3 (HIRIP3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of HIRA-interacting protein 3 (HIRIP3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of HIRA-interacting protein 3 (HIRIP3).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of HIRA-interacting protein 3 (HIRIP3).	[3]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.