Orexin receptor type 2 (Ox2R or OX<sub>2</sub>), 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.
The structure of the receptor has been solved to 2.5 ÃÂ resolution as a fusion protein bound to suvorexant using lipid-mediated crystallization.
OX<sub>2</sub> is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX<sub>1</sub>. OX<sub>2</sub> binds both orexin A and orexin B neuropeptides. OX<sub>2</sub> is involved in the central feedback mechanism that regulates feeding behaviour. Mice with enhanced OX<sub>2</sub> 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.