Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB8UEWR)

• DOT Name: Orexin/Hypocretin receptor type 1 (HCRTR1)
• Synonyms: Hypocretin receptor type 1; Orexin receptor type 1; Ox-1-R; Ox1-R; Ox1R
• Gene Name: HCRTR1
• UniProt ID: OX1R_HUMAN
• PDB ID: 4ZJ8; 4ZJC; 6TO7; 6TOD; 6TOS; 6TOT; 6TP3; 6TP4; 6TP6; 6TQ4; 6TQ6; 6TQ7; 6TQ9; 6V9S
• Pfam ID: PF00001
• Sequence:
  MEPSATPGAQMGVPPGSREPSPVPPDYEDEFLRYLWRDYLYPKQYEWVLIAAYVAVFVVA
  LVGNTLVCLAVWRNHHMRTVTNYFIVNLSLADVLVTAICLPASLLVDITESWLFGHALCK
  VIPYLQAVSVSVAVLTLSFIALDRWYAICHPLLFKSTARRARGSILGIWAVSLAIMVPQA
  AVMECSSVLPELANRTRLFSVCDERWADDLYPKIYHSCFFIVTYLAPLGLMAMAYFQIFR
  KLWGRQIPGTTSALVRNWKRPSDQLGDLEQGLSGEPQPRARAFLAEVKQMRARRKTAKML
  MVVLLVFALCYLPISVLNVLKRVFGMFRQASDREAVYACFTFSHWLVYANSAANPIIYNF
  LSGKFREQFKAAFSCCLPGLGPCGSLKAPSPRSSASHKSLSLQSRCSISKISEHVVLTSV
  TTVLP
• Function: Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. 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
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Orexin/Hypocretin receptor type 1 (HCRTR1).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Orexin/Hypocretin receptor type 1 (HCRTR1).	[3]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Orexin/Hypocretin receptor type 1 (HCRTR1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Orexin/Hypocretin receptor type 1 (HCRTR1).	[4]

References

• [1] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [2] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [3] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [4] 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.