Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8F8XR1)

• DOT Name: Probable G-protein coupled receptor 173 (GPR173)
• Synonyms: Super conserved receptor expressed in brain 3
• Gene Name: GPR173
• UniProt ID: GP173_HUMAN
• Pfam ID: PF00001
• Sequence:
  MANTTGEPEEVSGALSPPSASAYVKLVLLGLIMCVSLAGNAILSLLVLKERALHKAPYYF
  LLDLCLADGIRSAVCFPFVLASVRHGSSWTFSALSCKIVAFMAVLFCFHAAFMLFCISVT
  RYMAIAHHRFYAKRMTLWTCAAVICMAWTLSVAMAFPPVFDVGTYKFIREEDQCIFEHRY
  FKANDTLGFMLMLAVLMAATHAVYGKLLLFEYRHRKMKPVQMVPAISQNWTFHGPGATGQ
  AAANWIAGFGRGPMPPTLLGIRQNGHAASRRLLGMDEVKGEKQLGRMFYAITLLFLLLWS
  PYIVACYWRVFVKACAVPHRYLATAVWMSFAQAAVNPIVCFLLNKDLKKCLRTHAPCWGT
  GGAPAPREPYCVM
• Function: Is a receptor for the SMIM20 derived peptides Phoenixin-14 and Phoenixin-20. It mediates the Phoenixin-14 and Phoenixin-20 augmentation of gonadotropin-releasing hormone (GNRH) signaling in the hypothalamus and pituitary gland. In the ovary, it mediates the effects of Phoenixin-14 and Phoenixin-20 induced granulosa cell proliferation during follicular growth.
• Tissue Specificity: Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level) . Expressed at high levels in brain. Lower levels in small intestine. In brain regions, detected in all regions tested. Highest levels in the cerebellum and cerebral cortex.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Probable G-protein coupled receptor 173 (GPR173).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable G-protein coupled receptor 173 (GPR173).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Probable G-protein coupled receptor 173 (GPR173).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Probable G-protein coupled receptor 173 (GPR173).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Probable G-protein coupled receptor 173 (GPR173).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable G-protein coupled receptor 173 (GPR173).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable G-protein coupled receptor 173 (GPR173).	[7]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Probable G-protein coupled receptor 173 (GPR173).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable G-protein coupled receptor 173 (GPR173).	[5]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [8] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.