Details of Drug Off-Target (DOT)

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

• DOT Name: G-protein coupled receptor 26 (GPR26)
• Gene Name: GPR26
• Related Disease:
  Malignant glioma
  Acute myelogenous leukaemia
  Anxiety
  Anxiety disorder
• UniProt ID: GPR26_HUMAN
• Pfam ID: PF00001
• Sequence:
  MNSWDAGLAGLLVGTMGVSLLSNALVLLCLLHSADIRRQAPALFTLNLTCGNLLCTVVNM
  PLTLAGVVAQRQPAGDRLCRLAAFLDTFLAANSMLSMAALSIDRWVAVVFPLSYRAKMRL
  RDAALMVAYTWLHALTFPAAALALSWLGFHQLYASCTLCSRRPDERLRFAVFTGAFHALS
  FLLSFVVLCCTYLKVLKVARFHCKRIDVITMQTLVLLVDLHPSVRERCLEEQKRRRQRAT
  KKISTFIGTFLVCFAPYVITRLVELFSTVPIGSHWGVLSKCLAYSKAASDPFVYSLLRHQ
  YRKSCKEILNRLLHRRSIHSSGLTGDSHSQNILPVSE
• Function: Orphan receptor. Displays a significant level of constitutive activity. Its effect is mediated by G(s)-alpha protein that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP.
• Tissue Specificity: Highly expressed in the CNS, the highest expression is seen in the amygdala, hippocampus and thalamus. Weak expression is detected in testis. Down-regulated in glioblastoma.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant glioma	DISFXKOV	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Anxiety	DISIJDBA	Limited	Biomarker	[3]
Anxiety disorder	DISBI2BT	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 26 (GPR26).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G-protein coupled receptor 26 (GPR26).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of G-protein coupled receptor 26 (GPR26).	[5]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of G-protein coupled receptor 26 (GPR26).	[7]

References

• [1] The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas.Int J Oncol. 2009 Nov;35(5):1123-31. doi: 10.3892/ijo_00000428.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala.Neuroscience. 2011 Nov 24;196:203-14. doi: 10.1016/j.neuroscience.2011.08.069. Epub 2011 Sep 8.
• [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] 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.
• [6] 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.
• [7] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.