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Protein

Orexin

Gene

Hcrt

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. A modulation effect on luteinizing hormone-releasing hormone (LHRH) secretion also suggests a more minor contribution to the regulation of reproductive function. 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

  1. neuropeptide hormone activity Source: RGD
  2. type 1 hypocretin receptor binding Source: RGD
  3. type 2 hypocretin receptor binding Source: RGD

GO - Biological processi

  1. behavioral fear response Source: RGD
  2. eating behavior Source: RGD
  3. feeding behavior Source: RGD
  4. negative regulation of DNA replication Source: RGD
  5. negative regulation of potassium ion transport Source: RGD
  6. negative regulation of transmission of nerve impulse Source: RGD
  7. neuropeptide signaling pathway Source: UniProtKB-KW
  8. phospholipase C-activating G-protein coupled receptor signaling pathway Source: RGD
  9. positive regulation of calcium ion transport Source: RGD
  10. positive regulation of cytosolic calcium ion concentration Source: RGD
  11. positive regulation of transmission of nerve impulse Source: RGD
  12. protein kinase C-activating G-protein coupled receptor signaling pathway Source: RGD
  13. regulation of excitatory postsynaptic membrane potential Source: RGD
  14. regulation of neurotransmitter secretion Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Neuropeptide

Enzyme and pathway databases

ReactomeiREACT_326814. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
REACT_353304. G alpha (q) signalling events.

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, Ppox
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi2786. Hcrt.

Subcellular locationi

Rough endoplasmic reticulum
Note: Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses.

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. perinuclear region of cytoplasm Source: Ensembl
  3. rough endoplasmic reticulum Source: UniProtKB-SubCell
  4. secretory granule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 32321 PublicationAdd
BLAST
Peptidei33 – 6533Orexin-APRO_0000020270Add
BLAST
Peptidei69 – 9628Orexin-BPRO_0000020271Add
BLAST
Propeptidei97 – 13034PRO_0000020272Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei33 – 331Pyrrolidone carboxylic acid1 Publication
Disulfide bondi38 ↔ 44
Disulfide bondi39 ↔ 46
Modified residuei65 – 651Leucine amide
Modified residuei96 – 961Methionine amide

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

PRIDEiO55232.

Expressioni

Tissue specificityi

Produced by a small group of neurons restricted to the lateral and posterior hypothalamus and perifornical areas. Positive neurons project widely throughout the entire neuroaxis. Particularly abundant projections in the cerebral cortex, olfactory bulb, hippocampus, amygdala, septum, diagonal band of Broca, bed nucleus of the stria terminalis, thalamus, anterior and posterior hypothalamus, midbrain, brainstem, and spinal cord. Immunoreactivity reported in the enteric nervous system and pancreas. In small amount, also detected in the testis.

Developmental stagei

Detected as early as embryonic day 18, but expression increased dramatically after the third postnatal week.

Inductioni

By nutritional state, up-regulated by fasting, fluid deprivation and insulin-induced hypoglycemia. Orexin-A immunoreactivity varies diurnally and peaks during the dark phase, in the pons and the location of locus coeruleus.

Gene expression databases

GenevestigatoriO55232.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025547.

Structurei

3D structure databases

ProteinModelPortaliO55232.
SMRiO55232. Positions 33-65, 71-96.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the orexin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG70925.
GeneTreeiENSGT00390000014272.
HOGENOMiHOG000230990.
HOVERGENiHBG000256.
InParanoidiO55232.
KOiK05246.
OMAiKVSWATV.
OrthoDBiEOG7XSTHD.
PhylomeDBiO55232.
TreeFamiTF330756.

Family and domain databases

InterProiIPR001704. Orexin.
[Graphical view]
PANTHERiPTHR15173:SF2. PTHR15173:SF2. 1 hit.
PfamiPF02072. Orexin. 1 hit.
[Graphical view]
PIRSFiPIRSF037824. Orexin. 1 hit.
PRINTSiPR01091. OREXINPP.

Sequencei

Sequence statusi: Complete.

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

O55232-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNLPSTKVPW AAVTLLLLLL LPPALLSLGV DAQPLPDCCR QKTCSCRLYE
60 70 80 90 100
LLHGAGNHAA GILTLGKRRP GPPGLQGRLQ RLLQANGNHA AGILTMGRRA
110 120 130
GAELEPYPCP GRRCPTATAT ALAPRGGSRV
Length:130
Mass (Da):13,645
Last modified:June 1, 1998 - v1
Checksum:i00CAB259EDF2A404
GO

Mass spectrometryi

Molecular mass is 3558.7±0.1 Da from positions 33 - 65. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041241 mRNA. Translation: AAC40039.1.
AF019565 mRNA. Translation: AAC02933.1.
RefSeqiNP_037311.1. NM_013179.2.
UniGeneiRn.7628.

Genome annotation databases

EnsembliENSRNOT00000025547; ENSRNOP00000025547; ENSRNOG00000018892.
GeneIDi25723.
KEGGirno:25723.
UCSCiRGD:2786. rat.

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
AF041241 mRNA. Translation: AAC40039.1.
AF019565 mRNA. Translation: AAC02933.1.
RefSeqiNP_037311.1. NM_013179.2.
UniGeneiRn.7628.

3D structure databases

ProteinModelPortaliO55232.
SMRiO55232. Positions 33-65, 71-96.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025547.

Proteomic databases

PRIDEiO55232.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000025547; ENSRNOP00000025547; ENSRNOG00000018892.
GeneIDi25723.
KEGGirno:25723.
UCSCiRGD:2786. rat.

Organism-specific databases

CTDi3060.
RGDi2786. Hcrt.

Phylogenomic databases

eggNOGiNOG70925.
GeneTreeiENSGT00390000014272.
HOGENOMiHOG000230990.
HOVERGENiHBG000256.
InParanoidiO55232.
KOiK05246.
OMAiKVSWATV.
OrthoDBiEOG7XSTHD.
PhylomeDBiO55232.
TreeFamiTF330756.

Enzyme and pathway databases

ReactomeiREACT_326814. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
REACT_353304. G alpha (q) signalling events.

Miscellaneous databases

NextBioi607825.
PROiO55232.

Gene expression databases

GenevestigatoriO55232.

Family and domain databases

InterProiIPR001704. Orexin.
[Graphical view]
PANTHERiPTHR15173:SF2. PTHR15173:SF2. 1 hit.
PfamiPF02072. Orexin. 1 hit.
[Graphical view]
PIRSFiPIRSF037824. Orexin. 1 hit.
PRINTSiPR01091. OREXINPP.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 33-65 AND 69-96, PYROGLUTAMATE FORMATION AT GLN-33, MASS SPECTROMETRY.
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
  3. "Hypocretin/orexin, sleep and narcolepsy."
    Hungs M., Mignot E.
    Bioessays 23:397-408(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "To eat or to sleep? Orexin in the regulation of feeding and wakefulness."
    Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M.
    Annu. Rev. Neurosci. 24:429-458(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiOREX_RAT
AccessioniPrimary (citable) accession number: O55232
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: April 1, 2015
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.