Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SPUGC)

• DOT Name: Probable G-protein coupled receptor 75 (GPR75)
• Gene Name: GPR75
• Related Disease:
  Cardiovascular disease
  High blood pressure
  Neoplasm
  Prostate neoplasm
• UniProt ID: GPR75_HUMAN
• Pfam ID: PF00001
• Sequence:
  MNSTGHLQDAPNATSLHVPHSQEGNSTSLQEGLQDLIHTATLVTCTFLLAVIFCLGSYGN
  FIVFLSFFDPAFRKFRTNFDFMILNLSFCDLFICGVTAPMFTFVLFFSSASSIPDAFCFT
  FHLTSSGFIIMSLKTVAVIALHRLRMVLGKQPNRTASFPCTVLLTLLLWATSFTLATLAT
  LKTSKSHLCLPMSSLIAGKGKAILSLYVVDFTFCVAVVSVSYIMIAQTLRKNAQVRKCPP
  VITVDASRPQPFMGVPVQGGGDPIQCAMPALYRNQNYNKLQHVQTRGYTKSPNQLVTPAA
  SRLQLVSAINLSTAKDSKAVVTCVIIVLSVLVCCLPLGISLVQVVLSSNGSFILYQFELF
  GFTLIFFKSGLNPFIYSRNSAGLRRKVLWCLQYIGLGFFCCKQKTRLRAMGKGNLEVNRN
  KSSHHETNSAYMLSPKPQKKFVDQACGPSHSKESMVSPKISAGHQHCGQSSSTPINTRIE
  PYYSIYNSSPSQEESSPCNLQPVNSFGFANSYIAMHYHTTNDLVQEYDSTSAKQIPVPSV
• Function: G protein-coupled receptor that is activated by the chemokine CCL5/RANTES. Probably coupled to heterotrimeric Gq proteins, it stimulates inositol trisphosphate production and calcium mobilization upon activation. Together with CCL5/RANTES, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. CCL5/RANTES may also regulate insulin secretion by pancreatic islet cells through activation of this receptor.
• Tissue Specificity: Expressed at high levels in brain and spinal cord and at detectable levels in retinal pigment epithelium. In situ hybridization of adult eye sections localized transcripts only to the perivascular cells, surrounding retinal arterioles, in the ganglion cell/nerve fiber layer. Also expressed by islet cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable G-protein coupled receptor 75 (GPR75).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Probable G-protein coupled receptor 75 (GPR75).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Probable G-protein coupled receptor 75 (GPR75).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Probable G-protein coupled receptor 75 (GPR75).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Probable G-protein coupled receptor 75 (GPR75).	[8]

References

• [1] 20-HETE Signals Through G-Protein-Coupled Receptor GPR75 (G(q)) to Affect Vascular Function and Trigger Hypertension.Circ Res. 2017 May 26;120(11):1776-1788. doi: 10.1161/CIRCRESAHA.116.310525. Epub 2017 Mar 21.
• [2] DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.Epigenetics. 2014 Apr;9(4):503-12. doi: 10.4161/epi.27644. Epub 2014 Jan 17.
• [3] GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells.Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Feb;1865(2):158573. doi: 10.1016/j.bbalip.2019.158573. Epub 2019 Nov 21.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.