Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT61HEHW)

• DOT Name: Probable G-protein coupled receptor 34 (GPR34)
• Gene Name: GPR34
• UniProt ID: GPR34_HUMAN
• PDB ID: 8K4N; 8SAI; 8WRB
• Pfam ID: PF00001
• Sequence:
  MRSHTITMTTTSVSSWPYSSHRMRFITNHSDQPPQNFSATPNVTTCPMDEKLLSTVLTTS
  YSVIFIVGLVGNIIALYVFLGIHRKRNSIQIYLLNVAIADLLLIFCLPFRIMYHINQNKW
  TLGVILCKVVGTLFYMNMYISIILLGFISLDRYIKINRSIQQRKAITTKQSIYVCCIVWM
  LALGGFLTMIILTLKKGGHNSTMCFHYRDKHNAKGEAIFNFILVVMFWLIFLLIILSYIK
  IGKNLLRISKRRSKFPNSGKYATTARNSFIVLIIFTICFVPYHAFRFIYISSQLNVSSCY
  WKEIVHKTNEIMLVLSSFNSCLDPVMYFLMSSNIRKIMCQLLFRRFQGEPSRSESTSEFK
  PGYSLHDTSVAVKIQSSSKST
• Function: G-protein-coupled receptor of lysophosphatidylserine (LysoPS) that plays different roles in immune response. Acts a damage-sensing receptor that triggers tissue repair upon recognition of dying neutrophils. Mechanistically, apoptotic neutrophils release lysophosphatydilserine that are recognized by type 3 innate lymphoid cells (ILC3s) via GPR34, which activates downstream PI3K-AKT and RAS-ERK signaling pathways leading to STAT3 activation and IL-22 production. Plays an important role in microglial function, controlling morphology and phagocytosis.
• Tissue Specificity: Broadly expressed. Highly expressed on mast cells .

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable G-protein coupled receptor 34 (GPR34).	[1]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Probable G-protein coupled receptor 34 (GPR34).	[2]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Probable G-protein coupled receptor 34 (GPR34).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Probable G-protein coupled receptor 34 (GPR34).	[5]

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 34 (GPR34).	[4]

References

• [1] 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.
• [2] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [3] Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 2006 Dec 1;66(23):11187-93. doi: 10.1158/0008-5472.CAN-06-1274.
• [4] 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.
• [5] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.