Human Gene HCRT (ENST00000293330.1)
  Description: Homo sapiens hypocretin neuropeptide precursor (HCRT), mRNA. (from RefSeq NM_001524)
RefSeq Summary (NM_001524): 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. [provided by RefSeq, Jan 2010].
Gencode Transcript: ENST00000293330.1
Gencode Gene: ENSG00000161610.1
Transcript (Including UTRs)
   Position: hg38 chr17:42,184,060-42,185,452 Size: 1,393 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg38 chr17:42,184,154-42,185,365 Size: 1,212 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr17:42,184,060-42,185,452)mRNA (may differ from genome)Protein (131 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Orexin; AltName: Full=Hypocretin; Short=Hcrt; Contains: RecName: Full=Orexin-A; AltName: Full=Hypocretin-1; Short=Hcrt1; Contains: RecName: Full=Orexin-B; AltName: Full=Hypocretin-2; Short=Hcrt2; Flags: 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.
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="";

-  MalaCards Disease Associations
  MalaCards Gene Search: HCRT
Diseases sorted by gene-association score: narcolepsy 1* (1378), narcolepsy* (97), sleep disorder (38), idiopathic hypersomnia (28), recurrent hypersomnia (27), obstructive sleep apnea (18), rohhad (18), kleine-levin hibernation syndrome (17), restless legs syndrome (17), hypersomnia (13), sleep apnea (11), normal pressure hydrocephalus (11), acute disseminated encephalomyelitis (10), autoimmune encephalitis (10), cerebellar ataxia, deafness, and narcolepsy, autosomal dominant (9), cannabis dependence (9), von economo's disease (8), neuromyelitis optica (7), cluster headache (7), rem sleep behavior disorder (7), disease of mental health (6), morbid obesity (6), niemann-pick disease, type c1 (5), advanced sleep phase syndrome (5), migraine with or without aura 1 (5), guillain-barre syndrome (5), internuclear ophthalmoplegia (5), alobar holoprosencephaly (5), perry syndrome (5), prader-willi syndrome (4), cranioectodermal dysplasia 1 (4), obesity (2), parkinson disease, late-onset (1), central nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 34.85 RPKM in Brain - Hypothalamus
Total median expression: 36.55 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -11.8087-0.136 Picture PostScript Text
3' UTR -21.2094-0.226 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001704 - Orexin

Pfam Domains:
PF02072 - Prepro-orexin

Protein Data Bank (PDB) 3-D Structure
MuPIT help



- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.

ModBase Predicted Comparative 3D Structure on O43612
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005184 neuropeptide hormone activity
GO:0031771 type 1 hypocretin receptor binding
GO:0031772 type 2 hypocretin receptor binding

Biological Process:
GO:0001659 temperature homeostasis
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway
GO:0007218 neuropeptide signaling pathway
GO:0007268 chemical synaptic transmission
GO:0007631 feeding behavior
GO:0008156 negative regulation of DNA replication
GO:0010469 regulation of receptor activity
GO:0042755 eating behavior
GO:0043267 negative regulation of potassium ion transport
GO:0046928 regulation of neurotransmitter secretion
GO:0051928 positive regulation of calcium ion transport
GO:0051970 negative regulation of transmission of nerve impulse
GO:0051971 positive regulation of transmission of nerve impulse
GO:0060079 excitatory postsynaptic potential

Cellular Component:
GO:0005576 extracellular region
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005791 rough endoplasmic reticulum
GO:0008021 synaptic vesicle
GO:0030054 cell junction
GO:0030141 secretory granule
GO:0031410 cytoplasmic vesicle
GO:0045202 synapse
GO:0048471 perinuclear region of cytoplasm
GO:0098794 postsynapse

-  Descriptions from all associated GenBank mRNAs
  AF041240 - Homo sapiens prepro-orexin mRNA, complete cds.
JD255518 - Sequence 236542 from Patent EP1572962.
JD401053 - Sequence 382077 from Patent EP1572962.
JD475894 - Sequence 456918 from Patent EP1572962.
JD216787 - Sequence 197811 from Patent EP1572962.
AB463761 - Synthetic construct DNA, clone: pF1KB7189, Homo sapiens HCRT gene for hypocretin (orexin) neuropeptide precursor, without stop codon, in Flexi system.
BC111915 - Synthetic construct Homo sapiens clone IMAGE:40080741, MGC:133454 HCRT protein (HCRT) mRNA, encodes complete protein.
JD055694 - Sequence 36718 from Patent EP1572962.
JD566786 - Sequence 547810 from Patent EP1572962.
JD050084 - Sequence 31108 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein O43612 (Reactome details) participates in the following event(s):

R-HSA-389487 Orexin 2 receptor can bind orexin-B neuropeptide
R-HSA-389481 Orexin 1 receptor can bind orexin-A neuropeptide
R-HSA-749452 The Ligand:GPCR:Gq complex dissociates
R-HSA-749448 Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
R-HSA-379048 Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
R-HSA-389397 Orexin and neuropeptides FF and QRFP bind to their respective receptors
R-HSA-416476 G alpha (q) signalling events
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-388396 GPCR downstream signalling
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-372790 Signaling by GPCR
R-HSA-500792 GPCR ligand binding
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_001524, O43612, OREX_HUMAN, OX, PPORX, PPOX, uc002hzc.1
UCSC ID: ENST00000293330.1
RefSeq Accession: NM_001524
Protein: O43612 (aka OREX_HUMAN)
CCDS: CCDS11421.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.