Reviewed, UniProtKB/Swiss-Prot O55232 (OREX_RAT)

Names and origin

Protein names

Recommended name:
    Orexin
Alternative name(s):
    Hypocretin
      Short name=Hcrt
Cleaved into the following 2 chains:
    1- Recommended name:
            Orexin-A
        Alternative name(s):
            Hypocretin-1
              Short name=Hcrt1
    2- Recommended name:
            Orexin-B
        Alternative name(s):
            Hypocretin-2
              Short name=Hcrt2

Gene names

Name:	Hcrt
Synonyms:	Ox, Ppox

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	130 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. 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.
Subcellular location	Rough endoplasmic reticulum. Note: Associated with perikaryal rough endoplasmic reticulum as well as cytoplasmic large granular vesicles at synapses.
Tissue specificity	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 stage	Detected as early as embryonic day 18, but expression increased dramatically after the third postnatal week.
Induction	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.
Post-translational modification	Specific enzymatic cleavages at paired basic residues yield the different active peptides.
Sequence similarities	Belongs to the orexin family.
Mass spectrometry	Molecular mass is 3558.7±0.1 Da from positions 33 - 65. Determined by MALDI. Ref.1

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Domain	Signal
Molecular function	Neuropeptide
PTM	Amidation Cleavage on pair of basic residues Disulfide bond Pyrrolidone carboxylic acid
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger Inferred from mutant phenotype. Source: RGD activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from mutant phenotype. Source: RGD behavioral fear response Non-traceable author statement. Source: RGD eating behavior Inferred from direct assay. Source: RGD elevation of cytosolic calcium ion concentration Inferred from direct assay. Source: RGD negative regulation of DNA replication Inferred from direct assay. Source: RGD negative regulation of potassium ion transport Inferred from direct assay. Source: RGD negative regulation of transmission of nerve impulse Inferred from direct assay. Source: RGD neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of calcium ion transport Inferred from mutant phenotype. Source: RGD positive regulation of transmission of nerve impulse Inferred from direct assay. Source: RGD regulation of excitatory postsynaptic membrane potential Inferred from direct assay. Source: RGD regulation of neurotransmitter secretion Inferred from direct assay. Source: RGD
Cellular component	rough endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell secretory granule Ref.2 Inferred from direct assay. Source: RGD
Molecular function	neuropeptide hormone activity Inferred from direct assay. Source: RGD type 1 hypocretin receptor binding Inferred from direct assay. Source: RGD type 2 hypocretin receptor binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 32	32	Ref.1
	Peptide	33 – 65	33	Orexin-A Ref.1		PRO_0000020270
	Peptide	69 – 96	28	Orexin-B		PRO_0000020271
	Propeptide	97 – 130	34			PRO_0000020272
Amino acid modifications
	Modified residue	33	1	Pyrrolidone carboxylic acid
	Modified residue	65	1	Leucine amide
	Modified residue	96	1	Methionine amide
	Disulfide bond	38 ↔ 44
	Disulfide bond	39 ↔ 46

Sequences

	Sequence		Length	Mass (Da)
	O55232-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 00CAB259EDF2A404	FASTA	130	13,645
	10 20 30 40 50 60 MNLPSTKVPW AAVTLLLLLL LPPALLSLGV DAQPLPDCCR QKTCSCRLYE LLHGAGNHAA 70 80 90 100 110 120 GILTLGKRRP GPPGLQGRLQ RLLQANGNHA AGILTMGRRA GAELEPYPCP GRRCPTATAT 130 ALAPRGGSRV

References

[1]	"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior." Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., Williams S.C., Richardson J.A., Kozlowski G.P., Wilson S., Arch J.R.S., Buckingham R.E., Haynes A.C., Carr S.A., Annan R.S., McNulty D.E., Liu W.-S., Terrett J.A. , Elshourbagy N.A., Bergsma D.J., Yanagisawa M. Cell 92:573-585(1998) [PubMed: 9491897] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 33-65 AND 69-96, MASS SPECTROMETRY. Tissue: Brain.
[2]	"The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity." de Lecea L., Kilduff T.S., Peyron C., Gao X.-B., Foye P.E., Danielson P.E., Fukuhara C., Battenberg E.L.F., Gautvik V.T., Bartlett F.S. II, Frankel W.N., van den Pol A.N., Bloom F.E., Gautvik K.M., Sutcliffe J.G. Proc. Natl. Acad. Sci. U.S.A. 95:322-327(1998) [PubMed: 9419374] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley.
[3]	"Hypocretin/orexin, sleep and narcolepsy." Hungs M., Mignot E. Bioessays 23:397-408(2001) [PubMed: 11340621] [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(2001) [PubMed: 11283317] [Abstract] Cited for: REVIEW.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Qui dort dine - Issue 15 of October 2001

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF041241 mRNA. Translation: AAC40039.1. AF019565 mRNA. Translation: AAC02933.1.
IPI	IPI00196788.
RefSeq	NP_037311.1.
UniGene	Rn.7628
3D structure databases
SMR	O55232. Positions 33-65, 71-96.
ModBase	Search...
Protein-protein interaction databases
STRING	O55232.
Genome annotation databases
Ensembl	ENSRNOT00000025547; ENSRNOP00000025547; ENSRNOG00000018892; Rattus norvegicus. [Genome view]
GeneID	25723.
KEGG	rno:25723.
UCSC	NM_013179. rat.
Organism-specific databases
CTD	25723.
RGD	2786. Hcrt.
Phylogenomic databases
eggNOG	roNOG17366.
HOVERGEN	O55232.
InParanoid	O55232.
OMA	PCPGRRC.
OrthoDB	EOG96X1TV.
PhylomeDB	O55232.
Gene expression databases
ArrayExpress	O55232.
Genevestigator	O55232.
GermOnline	ENSRNOG00000018892. Rattus norvegicus.
Family and domain databases
InterPro	IPR001704. Orexin. [Graphical view]
PANTHER	PTHR15173. Orexin. 1 hit.
Pfam	PF02072. Orexin. 1 hit. [Graphical view]
PRINTS	PR01091. OREXINPP.
ProtoNet	Search...
Other Resources
NextBio	607825.

Entry information

Entry name

OREX_RAT

Accession

Primary (citable) accession number: O55232

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	January 19, 2010
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)