Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYDO1U7)

• DOT Name: G-protein coupled receptor 171 (GPR171)
• Synonyms: G-protein coupled receptor H963
• Gene Name: GPR171
• Related Disease:
  Mental disorder
  Usher syndrome type 3
• UniProt ID: GP171_HUMAN
• Pfam ID: PF00001
• Sequence:
  MTNSSFFCPVYKDLEPFTYFFYLVFLVGIIGSCFATWAFIQKNTNHRCVSIYLINLLTAD
  FLLTLALPVKIVVDLGVAPWKLKIFHCQVTACLIYINMYLSIIFLAFVSIDRCLQLTHSC
  KIYRIQEPGFAKMISTVVWLMVLLIMVPNMMIPIKDIKEKSNVGCMEFKKEFGRNWHLLT
  NFICVAIFLNFSAIILISNCLVIRQLYRNKDNENYPNVKKALINILLVTTGYIICFVPYH
  IVRIPYTLSQTEVITDCSTRISLFKAKEATLLLAVSNLCFDPILYYHLSKAFRSKVTETF
  ASPKETKAQKEKLRCENNA
• Function: G-protein coupled receptor for Big LEN, a 16-amino acid neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N). Acts through a G(i)-alpha-mediated pathway in response to Big LEN. Big LEN-GPR171 system plays an important role in regulating feeding and metabolism. Also plays a role in modulating fear and anxiety-like behaviors in the basolateral amygdala. Big LEN-GPR171 modulates the mu-type opioid receptor signaling and antinociception. Acts as a negative regulator T cell function.
• Tissue Specificity: Expressed in both T-cell subsets and natural killer cells, while it is undetectable in B cells or CD14(+) monocytes. Expressed in peripheral blood mononuclear cells (PBMC) and Jurkat cells (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
Mental disorder	DIS3J5R8	Strong	Biomarker	[1]
Usher syndrome type 3	DISRAL84	Strong	Genetic Variation	[2]

1 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 171 (GPR171).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of G-protein coupled receptor 171 (GPR171).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of G-protein coupled receptor 171 (GPR171).	[5]

References

• [1] The BigLEN-GPR171 Peptide Receptor System Within the Basolateral Amygdala Regulates Anxiety-Like Behavior and Contextual Fear Conditioning.Neuropsychopharmacology. 2017 Dec;42(13):2527-2536. doi: 10.1038/npp.2017.79. Epub 2017 Apr 20.
• [2] Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet. 2001 Oct;69(4):673-84. doi: 10.1086/323610. Epub 2001 Aug 27.
• [3] 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.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.