Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXOY5NW)

• DOT Name: G-protein coupled receptor 135 (GPR135)
• Gene Name: GPR135
• Related Disease:
  Obsessive compulsive disorder
  Myocardial infarction
  Lung cancer
  Lung carcinoma
  Lung neoplasm
• UniProt ID: GP135_HUMAN
• Pfam ID: PF00001
• Sequence:
  MEEPQPPRPPASMALLGSQHSGAPSAAGPPGGTSSAATAAVLSFSTVATAALGNLSDASG
  GGTAAAPGGGGLGGSGAAREAGAAVRRPLGPEAAPLLSHGAAVAAQALVLLLIFLLSSLG
  NCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAAAAGPW
  RGFCAASRFFSSCFGIVSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGF
  SLPWELLGAPRELAAAQSFHGCLYRTSPDPAQLGAAFSVGLVVACYLLPFLLMCFCHYHI
  CKTVRLSDVRVRPVNTYARVLRFFSEVRTATTVLIMIVFVICCWGPYCFLVLLAAARQAQ
  TMQAPSLLSVVAVWLTWANGAINPVIYAIRNPNISMLLGRNREEGYRTRNVDAFLPSQGP
  GLQARSRSRLRNRYANRLGACNRMSSSNPASGVAGDVAMWARKNPVVLFCREGPPEPVTA
  VTKQPKSEAGDTSL
• Function: Orphan receptor. Has spontaneous activity for beta-arrestin recruitment. Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsessive compulsive disorder	DIS1ZMM2	Definitive	Genetic Variation	[1]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	Limited	Biomarker	[3]
Lung carcinoma	DISTR26C	Limited	Biomarker	[3]
Lung neoplasm	DISVARNB	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of G-protein coupled receptor 135 (GPR135).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of G-protein coupled receptor 135 (GPR135).	[11]

8 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 G-protein coupled receptor 135 (GPR135).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G-protein coupled receptor 135 (GPR135).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of G-protein coupled receptor 135 (GPR135).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of G-protein coupled receptor 135 (GPR135).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of G-protein coupled receptor 135 (GPR135).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of G-protein coupled receptor 135 (GPR135).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of G-protein coupled receptor 135 (GPR135).	[12]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of G-protein coupled receptor 135 (GPR135).	[13]

References

• [1] Sex differences in the genetic architecture of obsessive-compulsive disorder.Am J Med Genet B Neuropsychiatr Genet. 2019 Sep;180(6):351-364. doi: 10.1002/ajmg.b.32687. Epub 2018 Nov 20.
• [2] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [3] Asbestos-associated genome-wide DNA methylation changes in lung cancer.Int J Cancer. 2017 Nov 15;141(10):2014-2029. doi: 10.1002/ijc.30897. Epub 2017 Aug 2.
• [4] 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.
• [5] 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.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] 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.
• [13] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.