Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNJBJC1)

• DOT Name: Galanin receptor type 2 (GALR2)
• Synonyms: GAL2-R; GALR-2
• Gene Name: GALR2
• UniProt ID: GALR2_HUMAN
• PDB ID: 7WQ4; 7XBD; 7XJK; 7XJL
• Pfam ID: PF00001
• Sequence:
  MNVSGCPGAGNASQAGGGGGWHPEAVIVPLLFALIFLVGTVGNTLVLAVLLRGGQAVSTT
  NLFILNLGVADLCFILCCVPFQATIYTLDGWVFGSLLCKAVHFLIFLTMHASSFTLAAVS
  LDRYLAIRYPLHSRELRTPRNALAAIGLIWGLSLLFSGPYLSYYRQSQLANLTVCHPAWS
  APRRRAMDICTFVFSYLLPVLVLGLTYARTLRYLWRAVDPVAAGSGARRAKRKVTRMILI
  VAALFCLCWMPHHALILCVWFGQFPLTRATYALRILSHLVSYANSCVNPIVYALVSKHFR
  KGFRTICAGLLGRAPGRASGRVCAAARGTHSGSVLERESSDLLHMSEAAGALRPCPGASQ
  PCILEPCPGPSWQGPKAGDSILTVDVA
• Function: Receptor for the hormone galanin and GALP. Receptor for the hormone spexin-1. The activity of this receptor is mediated by G proteins that activate the phospholipase C/protein kinase C pathway (via G(q)) and that inhibit adenylyl cyclase (via G(i)).
• Tissue Specificity: Expressed abundantly within the central nervous system in both hypothalamus and hippocampus. In peripheral tissues, the strongest expression was observed in heart, kidney, liver, and small intestine.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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 Galanin receptor type 2 (GALR2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Galanin receptor type 2 (GALR2).	[6]

9 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 Galanin receptor type 2 (GALR2).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Galanin receptor type 2 (GALR2).	[3]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Galanin receptor type 2 (GALR2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Galanin receptor type 2 (GALR2).	[5]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Galanin receptor type 2 (GALR2).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Galanin receptor type 2 (GALR2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Galanin receptor type 2 (GALR2).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Galanin receptor type 2 (GALR2).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Galanin receptor type 2 (GALR2).	[9]

References

• [1] 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.
• [2] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [4] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.