HCRT

This gene encodes a hypothalamic neuropeptide precursor protein that gives rise to two mature neuropeptides, orexin A and orexin B, by proteolytic processing. Orexin A and orexin B, which bind to orphan G-protein coupled receptors HCRTR1 and HCRTR2, function in the regulation of sleep and arousal. This neuropeptide arrangement may also play a role in feeding behavior, metabolism, and homeostasis.

Full Name

Hypocretin Neuropeptide Precursor

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.

Biological Process

Chemical synaptic transmission Source: ProtInc
Eating behavior Source: GO_Central
Excitatory postsynaptic potential Source: Ensembl
Negative regulation of DNA replication Source: Ensembl
Negative regulation of potassium ion transport Source: Ensembl
Negative regulation of transmission of nerve impulse Source: Ensembl
Neuropeptide signaling pathway Source: UniProtKB-KW
Phospholipase C-activating G protein-coupled receptor signaling pathway Source: Ensembl
Positive regulation of calcium ion transport Source: Ensembl
Positive regulation of cold-induced thermogenesis Source: YuBioLab
Positive regulation of cytosolic calcium ion concentration Source: Ensembl
Positive regulation of transmission of nerve impulse Source: GO_Central
Protein kinase C-activating G protein-coupled receptor signaling pathway Source: Ensembl
Regulation of neurotransmitter secretion Source: GO_Central
Response to starvation Source: GO_Central
Sleep Source: GO_Central
Temperature homeostasis Source: GO_Central

Cellular Location

Rough endoplasmic reticulum; Cytoplasmic vesicle; Synapse. Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses.

Involvement in disease

Narcolepsy 1 (NRCLP1):
The disease is caused by variants affecting the gene represented in this entry. 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. Neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, 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.

PTM

Specific enzymatic cleavages at paired basic residues yield the different active peptides.