Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK8XH8M)

• DOT Name: G-protein coupled receptor 61 (GPR61)
• Synonyms: Biogenic amine receptor-like G-protein coupled receptor
• Gene Name: GPR61
• Related Disease:
  Autoimmune disease
  Non-insulin dependent diabetes
• UniProt ID: GPR61_HUMAN
• PDB ID: 8KGK; 8TB0
• Pfam ID: PF00001
• Sequence:
  MESSPIPQSSGNSSTLGRVPQTPGPSTASGVPEVGLRDVASESVALFFMLLLDLTAVAGN
  AAVMAVIAKTPALRKFVFVFHLCLVDLLAALTLMPLAMLSSSALFDHALFGEVACRLYLF
  LSVCFVSLAILSVSAINVERYYYVVHPMRYEVRMTLGLVASVLVGVWVKALAMASVPVLG
  RVSWEEGAPSVPPGCSLQWSHSAYCQLFVVVFAVLYFLLPLLLILVVYCSMFRVARVAAM
  QHGPLPTWMETPRQRSESLSSRSTMVTSSGAPQTTPHRTFGGGKAAVVLLAVGGQFLLCW
  LPYFSFHLYVALSAQPISTGQVESVVTWIGYFCFTSNPFFYGCLNRQIRGELSKQFVCFF
  KPAPEEELRLPSREGSIEENFLQFLQGTGCPSESWVSRPLPSPKQEPPAVDFRIPGQIAE
  ETSEFLEQQLTSDIIMSDSYLRPAASPRLES
• Function: Orphan G-protein coupled receptor. Constitutively activates the G(s)-alpha/cAMP signaling pathway. Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization. May be involved in the regulation of food intake and body weight.
• Tissue Specificity: Expressed in brain; detected in frontal and temporal lobes, occipital pole, amygdala and hippocampus . Also expressed in testis and T cells, B cells, and monocyte . Low expression in many other tissues . Widely expressed in the hippocampus (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[2]

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 affects the methylation of G-protein coupled receptor 61 (GPR61).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of G-protein coupled receptor 61 (GPR61).	[4]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of G-protein coupled receptor 61 (GPR61).	[5]

References

• [1] N-glycosylation and expression in human tissues of the orphan GPR61 receptor.FEBS Open Bio. 2017 Nov 20;7(12):1982-1993. doi: 10.1002/2211-5463.12339. eCollection 2017 Dec.
• [2] An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.Nat Commun. 2014 Dec 12;5:5719. doi: 10.1038/ncomms6719.
• [3] 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.
• [4] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [5] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.