Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2 (HcrtR2), is a protein that in humans is encoded by the HCRTR2 gene. It should not be confused for the protein CD200R1 which shares the alias OX2R but is a distinct, unrelated gene located on the human chromosome 3.

Structure

The structure of the receptor has been solved to 2.5 Å resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization.

Function

OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced OX2 signaling are resistant to high-fat diet-induced obesity.

This receptor is activated by orexin, which is a wake-promoting hypothalamic neuropeptide that acts as a critical regulator of sleep in animals as Zebrafish or Mammals. This protein has mutations in Astyanax mexicanus that reduces the sleep needs of the cavefish.

Ligands

Agonists

  • Danavorexton/TAK-925 – selective OX2 receptor agonist
  • Firazorexton/TAK-994 – selective OX2 receptor agonist
  • Orexins – dual OX1 and OX2 receptor agonists Orexin-A – approximately equipotent at the OX1 and OX2 receptors Orexin-B – approximately 5- to 10-fold selectivity for the OX2 receptor over the OX1 receptor
  • SB-668875 – selective OX2 receptor agonist
  • Suntinorexton – selective OX2 receptor agonist
  • Oveporexton/TAK-861 – selective OX2 receptor agonist
  • Cleminorexton - selective OX2 receptor agonist

Antagonists

See also

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.