Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT81CA1Z)

• DOT Name: Probable G-protein coupled receptor 153 (GPR153)
• Synonyms: G-protein coupled receptor PGR1
• Gene Name: GPR153
• Related Disease:
  Schizophrenia
  Malignant mesothelioma
• UniProt ID: GP153_HUMAN
• Pfam ID: PF00001
• Sequence:
  MSDERRLPGSAVGWLVCGGLSLLANAWGILSVGAKQKKWKPLEFLLCTLAATHMLNVAVP
  IATYSVVQLRRQRPDFEWNEGLCKVFVSTFYTLTLATCFSVTSLSYHRMWMVCWPVNYRL
  SNAKKQAVHTVMGIWMVSFILSALPAVGWHDTSERFYTHGCRFIVAEIGLGFGVCFLLLV
  GGSVAMGVICTAIALFQTLAVQVGRQADRRAFTVPTIVVEDAQGKRRSSIDGSEPAKTSL
  QTTGLVTTIVFIYDCLMGFPVLVVSFSSLRADASAPWMALCVLWCSVAQALLLPVFLWAC
  DRYRADLKAVREKCMALMANDEESDDETSLEGGISPDLVLERSLDYGYGGDFVALDRMAK
  YEISALEGGLPQLYPLRPLQEDKMQYLQVPPTRRFSHDDADVWAAVPLPAFLPRWGSGED
  LAALAHLVLPAGPERRRASLLAFAEDAPPSRARRRSAESLLSLRPSALDSGPRGARDSPP
  GSPRRRPGPGPRSASASLLPDAFALTAFECEPQALRRPPGPFPAAPAAPDGADPGEAPTP
  PSSAQRSPGPRPSAHSHAGSLRPGLSASWGEPGGLRAAGGGGSTSSFLSSPSESSGYATL
  HSDSLGSAS
• Function: Orphan receptor.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Malignant mesothelioma	DISTHJGH	Limited	Biomarker	[2]

1 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 Probable G-protein coupled receptor 153 (GPR153).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable G-protein coupled receptor 153 (GPR153).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Probable G-protein coupled receptor 153 (GPR153).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Probable G-protein coupled receptor 153 (GPR153).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Probable G-protein coupled receptor 153 (GPR153).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable G-protein coupled receptor 153 (GPR153).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Probable G-protein coupled receptor 153 (GPR153).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Probable G-protein coupled receptor 153 (GPR153).	[9]

References

• [1] Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
• [2] Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung.Lung Cancer. 2005 Feb;47(2):193-204. doi: 10.1016/j.lungcan.2004.08.003.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] 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.