Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQF4U7B)

• DOT Name: Orexin receptor type 2 (HCRTR2)
• Synonyms: Ox-2-R; Ox2-R; Ox2R; Hypocretin receptor type 2
• Gene Name: HCRTR2
• UniProt ID: OX2R_HUMAN
• PDB ID: 4S0V; 5WQC; 5WS3; 6TPG; 6TPJ; 6TPN; 7L1U; 7L1V; 7SQO; 7SR8; 7XRR
• Pfam ID: PF00001 ; PF03827
• Sequence:
  MSGTKLEDSPPCRNWSSASELNETQEPFLNPTDYDDEEFLRYLWREYLHPKEYEWVLIAG
  YIIVFVVALIGNVLVCVAVWKNHHMRTVTNYFIVNLSLADVLVTITCLPATLVVDITETW
  FFGQSLCKVIPYLQTVSVSVSVLTLSCIALDRWYAICHPLMFKSTAKRARNSIVIIWIVS
  CIIMIPQAIVMECSTVFPGLANKTTLFTVCDERWGGEIYPKMYHICFFLVTYMAPLCLMV
  LAYLQIFRKLWCRQIPGTSSVVQRKWKPLQPVSQPRGPGQPTKSRMSAVAAEIKQIRARR
  KTARMLMIVLLVFAICYLPISILNVLKRVFGMFAHTEDRETVYAWFTFSHWLVYANSAAN
  PIIYNFLSGKFREEFKAAFSCCCLGVHHRQEDRLTRGRTSTESRKSLTTQISNFDNISKL
  SEQVVLTSISTLPAANGAGPLQNW
• Function: Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides. Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Orexin and neuropeptides FF and QRFP bind to their respective receptors (R-HSA-389397)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Orexin receptor type 2 (HCRTR2).	[1]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Orexin receptor type 2 (HCRTR2).	[3]

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 Orexin receptor type 2 (HCRTR2).	[2]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] 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.
• [3] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.