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Protein

Orexin

Gene

HCRT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionNeuropeptide

Enzyme and pathway databases

ReactomeiR-HSA-389397 Orexin and neuropeptides FF and QRFP bind to their respective receptors
R-HSA-416476 G alpha (q) signalling events
SIGNORiO43612

Names & Taxonomyi

Protein namesi
Recommended name:
Orexin
Alternative name(s):
Hypocretin
Short name:
Hcrt
Cleaved into the following 2 chains:
Alternative name(s):
Hypocretin-1
Short name:
Hcrt1
Alternative name(s):
Hypocretin-2
Short name:
Hcrt2
Gene namesi
Name:HCRT
Synonyms:OX, PPORX, PPOX
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000161610.1
HGNCiHGNC:4847 HCRT
MIMi602358 gene
neXtProtiNX_O43612

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasmic vesicle, Endoplasmic reticulum, Synapse

Pathology & Biotechi

Involvement in diseasei

Narcolepsy 1 (NRCLP1)1 Publication
The disease is caused by mutations 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.
Disease descriptionNeurological 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.
See also OMIM:161400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01163316L → R in NRCLP1; early-onset; impaired trafficking and processing. 1 PublicationCorresponds to variant dbSNP:rs104894574EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3060
MalaCardsiHCRT
MIMi161400 phenotype
OpenTargetsiENSG00000161610
Orphaneti83465 Narcolepsy without cataplexy
2073 Narcolepsy-cataplexy
PharmGKBiPA29221

Chemistry databases

DrugBankiDB03088 Pyroglutamic Acid

Polymorphism and mutation databases

BioMutaiHCRT

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 33By similarityAdd BLAST33
PeptideiPRO_000002026134 – 66Orexin-AAdd BLAST33
PeptideiPRO_000002026270 – 97Orexin-BAdd BLAST28
PropeptideiPRO_000002026398 – 131Add BLAST34

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Pyrrolidone carboxylic acidBy similarity1
Disulfide bondi39 ↔ 45
Disulfide bondi40 ↔ 47
Modified residuei66Leucine amideBy similarity1
Modified residuei97Methionine amideBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiO43612
PeptideAtlasiO43612
PRIDEiO43612
ProteomicsDBi49080

Miscellaneous databases

PMAP-CutDBiO43612

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000161610 Expressed in 53 organ(s), highest expression level in hypothalamus
CleanExiHS_HCRT
HS_PPOX
GenevisibleiO43612 HS

Organism-specific databases

HPAiCAB004758

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

IntActiO43612, 1 interactor
STRINGi9606.ENSP00000293330

Structurei

Secondary structure

1131
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO43612
SMRiO43612
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43612

Family & Domainsi

Sequence similaritiesi

Belongs to the orexin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J4FI Eukaryota
ENOG410Y5WS LUCA
GeneTreeiENSGT00390000014272
HOGENOMiHOG000230990
HOVERGENiHBG000256
InParanoidiO43612
KOiK05246
OMAiSECCRQP
OrthoDBiEOG091G0K5S
PhylomeDBiO43612
TreeFamiTF330756

Family and domain databases

InterProiView protein in InterPro
IPR001704 Orexin
PANTHERiPTHR15173 PTHR15173, 1 hit
PfamiView protein in Pfam
PF02072 Orexin, 1 hit
PIRSFiPIRSF037824 Orexin, 1 hit
PRINTSiPR01091 OREXINPP

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O43612-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNLPSTKVSW AAVTLLLLLL LLPPALLSSG AAAQPLPDCC RQKTCSCRLY
60 70 80 90 100
ELLHGAGNHA AGILTLGKRR SGPPGLQGRL QRLLQASGNH AAGILTMGRR
110 120 130
AGAEPAPRPC LGRRCSAPAA ASVAPGGQSG I
Length:131
Mass (Da):13,363
Last modified:June 1, 1998 - v1
Checksum:i139D9C33E39E4EF1
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01163316L → R in NRCLP1; early-onset; impaired trafficking and processing. 1 PublicationCorresponds to variant dbSNP:rs104894574EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041240 mRNA Translation: AAC39600.1
AF118885 Genomic DNA Translation: AAD24459.1
CCDSiCCDS11421.1
RefSeqiNP_001515.1, NM_001524.1
UniGeneiHs.158348

Genome annotation databases

EnsembliENST00000293330; ENSP00000293330; ENSG00000161610
GeneIDi3060
KEGGihsa:3060
UCSCiuc002hzc.1 human

Similar proteinsi

Cross-referencesi

Web resourcesi

Protein Spotlight

Qui dort dine - Issue 15 of October 2001

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041240 mRNA Translation: AAC39600.1
AF118885 Genomic DNA Translation: AAD24459.1
CCDSiCCDS11421.1
RefSeqiNP_001515.1, NM_001524.1
UniGeneiHs.158348

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CQ0NMR-A71-97[»]
1R02NMR-A34-66[»]
1UVQX-ray1.80C1-12[»]
1WSONMR-A34-66[»]
ProteinModelPortaliO43612
SMRiO43612
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO43612, 1 interactor
STRINGi9606.ENSP00000293330

Chemistry databases

DrugBankiDB03088 Pyroglutamic Acid

Polymorphism and mutation databases

BioMutaiHCRT

Proteomic databases

PaxDbiO43612
PeptideAtlasiO43612
PRIDEiO43612
ProteomicsDBi49080

Protocols and materials databases

DNASUi3060
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000293330; ENSP00000293330; ENSG00000161610
GeneIDi3060
KEGGihsa:3060
UCSCiuc002hzc.1 human

Organism-specific databases

CTDi3060
DisGeNETi3060
EuPathDBiHostDB:ENSG00000161610.1
GeneCardsiHCRT
HGNCiHGNC:4847 HCRT
HPAiCAB004758
MalaCardsiHCRT
MIMi161400 phenotype
602358 gene
neXtProtiNX_O43612
OpenTargetsiENSG00000161610
Orphaneti83465 Narcolepsy without cataplexy
2073 Narcolepsy-cataplexy
PharmGKBiPA29221
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J4FI Eukaryota
ENOG410Y5WS LUCA
GeneTreeiENSGT00390000014272
HOGENOMiHOG000230990
HOVERGENiHBG000256
InParanoidiO43612
KOiK05246
OMAiSECCRQP
OrthoDBiEOG091G0K5S
PhylomeDBiO43612
TreeFamiTF330756

Enzyme and pathway databases

ReactomeiR-HSA-389397 Orexin and neuropeptides FF and QRFP bind to their respective receptors
R-HSA-416476 G alpha (q) signalling events
SIGNORiO43612

Miscellaneous databases

EvolutionaryTraceiO43612
GenomeRNAii3060
PMAP-CutDBiO43612
PROiPR:O43612
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000161610 Expressed in 53 organ(s), highest expression level in hypothalamus
CleanExiHS_HCRT
HS_PPOX
GenevisibleiO43612 HS

Family and domain databases

InterProiView protein in InterPro
IPR001704 Orexin
PANTHERiPTHR15173 PTHR15173, 1 hit
PfamiView protein in Pfam
PF02072 Orexin, 1 hit
PIRSFiPIRSF037824 Orexin, 1 hit
PRINTSiPR01091 OREXINPP
ProtoNetiSearch...

Entry informationi

Entry nameiOREX_HUMAN
AccessioniPrimary (citable) accession number: O43612
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: September 12, 2018
This is version 157 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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Main funding by: National Institutes of Health

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