. "FUNCTION: Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity. SUBCELLULAR LOCATION: Rough endoplasmic reticulum (By similarity). Cytoplasmic vesicle (By similarity). Cell junction, synapse (By similarity). Note=Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses (By similarity). TISSUE SPECIFICITY: Abundantly expressed in subthalamic nucleus but undetectable in other brain regions tested (hypothalamus was not tested) and in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas. PTM: Specific enzymatic cleavages at paired basic residues yield the different active peptides. DISEASE: Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:161400]. Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. Note=Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients. SIMILARITY: Belongs to the orexin family. WEB RESOURCE: Name=Protein Spotlight; Note=Qui dort dine - Issue 15 of October 2001; URL=\"http://web.expasy.org/spotlight/back_issues/sptlt015.shtml\"; GENE SYNONYMS:HCRT OX PPORX PPOX. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License."^^ . "SEQUENCE 131 AA; 13363 MW; 139D9C33E39E4EF1 CRC64;"^^ . . . . . "OREX_HUMAN"^^ . "HCRT"^^ . "Hypocretin"^^ . "Hypocretin-1"^^ . "Orexin-B"^^ . "Hcrt"^^ . "Hcrt2"^^ . "Orexin-A"^^ . "Hcrt1"^^ . "Hypocretin-2"^^ . . . . . "MNLPSTKVSWAAVTLLLLLLLLPPALLSSGAAAQPLPDCCRQKTCSCRLYELLHGAGNHAAGILTLGKRRSGPPGLQGRLQRLLQASGNHAAGILTMGRRAGAEPAPRPCLGRRCSAPAAASVAPGGQSGI"^^ . "Orexin"^^ .