Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI9OG9Y)

• DOT Name: Probable G-protein coupled receptor 174 (GPR174)
• Gene Name: GPR174
• UniProt ID: GP174_HUMAN
• PDB ID: 7XV3; 8IZB; 8KH5
• Pfam ID: PF00001
• Sequence:
  MPANYTCTRPDGDNTDFRYFIYAVTYTVILVPGLIGNILALWVFYGYMKETKRAVIFMIN
  LAIADLLQVLSLPLRIFYYLNHDWPFGPGLCMFCFYLKYVNMYASIYFLVCISVRRFWFL
  MYPFRFHDCKQKYDLYISIAGWLIICLACVLFPLLRTSDDTSGNRTKCFVDLPTRNVNLA
  QSVVMMTIGELIGFVTPLLIVLYCTWKTVLSLQDKYPMAQDLGEKQKALKMILTCAGVFL
  ICFAPYHFSFPLDFLVKSNEIKSCLARRVILIFHSVALCLASLNSCLDPVIYYFSTNEFR
  RRLSRQDLHDSIQLHAKSFVSNHTASTMTPELC
• Function: G-protein-coupled receptor of lysophosphatidylserine (LysoPS) that plays different roles in immune response. Plays a negative role in regulatory T-cell accumulation and homeostasis. Under inflammatory conditions where LysoPS production increases, contributes to the down-regulation of regulatory T-cell activity to favor effector response. Mediates the suppression of IL-2 production in activated T-lymphocytes leading to inhibition of growth, proliferation and differentiation of T-cells. Mechanistically, acts via G(12)/G(13)-containing heterotrimeric G proteins to trigger elevated cyclic AMP levels and protein kinase A/PKA activity, which may in turn act to antagonize proximal TCR signaling. Plays an important role in the initial period of sepsis through the regulation of macrophage polarization and pro- and anti-inflammatory cytokine secretions. Upon testosterone treatment, acts as a receptor for CCL21 and subsequently triggers through G(q)-alpha and G(12)/G(13) proteins a calcium flux leading to chemotactic effects on activated B-cells. Signals via GNA13 and PKA to promote CD86 up-regulation by follicular B-cells.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Probable G-protein coupled receptor 174 (GPR174).	[1]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Probable G-protein coupled receptor 174 (GPR174).	[3]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Probable G-protein coupled receptor 174 (GPR174).	[4]

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 174 (GPR174).	[2]

References

• [1] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [2] 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.
• [3] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [4] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.