ID   OREX_RAT                Reviewed;         130 AA.
AC   O55232;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   16-JUN-2009, entry version 66.
DE   RecName: Full=Orexin;
DE   AltName: Full=Hypocretin;
DE            Short=Hcrt;
DE   Contains:
DE     RecName: Full=Orexin-A;
DE     AltName: Full=Hypocretin-1;
DE              Short=Hcrt1;
DE   Contains:
DE     RecName: Full=Orexin-B;
DE     AltName: Full=Hypocretin-2;
DE              Short=Hcrt2;
DE   Flags: Precursor;
GN   Name=Hcrt; Synonyms=Ox, Ppox;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 33-65 AND 69-96, AND
RP   MASS SPECTROMETRY.
RC   TISSUE=Brain;
RX   MEDLINE=98150861; PubMed=9491897; DOI=10.1016/S0092-8674(00)80949-6;
RA   Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M.,
RA   Tanaka H., Williams S.C., Richardson J.A., Kozlowski G.P., Wilson S.,
RA   Arch J.R.S., Buckingham R.E., Haynes A.C., Carr S.A., Annan R.S.,
RA   McNulty D.E., Liu W.-S., Terrett J.A., Elshourbagy N.A., Bergsma D.J.,
RA   Yanagisawa M.;
RT   "Orexins and orexin receptors: a family of hypothalamic neuropeptides
RT   and G protein-coupled receptors that regulate feeding behavior.";
RL   Cell 92:573-585(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RX   MEDLINE=98081872; PubMed=9419374; DOI=10.1073/pnas.95.1.322;
RA   de Lecea L., Kilduff T.S., Peyron C., Gao X.-B., Foye P.E.,
RA   Danielson P.E., Fukuhara C., Battenberg E.L.F., Gautvik V.T.,
RA   Bartlett F.S. II, Frankel W.N., van den Pol A.N., Bloom F.E.,
RA   Gautvik K.M., Sutcliffe J.G.;
RT   "The hypocretins: hypothalamus-specific peptides with neuroexcitatory
RT   activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:322-327(1998).
RN   [3]
RP   REVIEW.
RX   MEDLINE=21237974; PubMed=11340621; DOI=10.1002/bies.1058;
RA   Hungs M., Mignot E.;
RT   "Hypocretin/orexin, sleep and narcolepsy.";
RL   Bioessays 23:397-408(2001).
RN   [4]
RP   REVIEW.
RX   MEDLINE=21178476; PubMed=11283317; DOI=10.1146/annurev.neuro.24.1.429;
RA   Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M.;
RT   "To eat or to sleep? Orexin in the regulation of feeding and
RT   wakefulness.";
RL   Annu. Rev. Neurosci. 24:429-458(2001).
CC   -!- FUNCTION: Neuropeptides that play a significant role in the
CC       regulation of food intake and sleep-wakefulness, possibly by
CC       coordinating the complex behavioral and physiologic responses of
CC       these complementary homeostatic functions. A broader role in the
CC       homeostatic regulation of energy metabolism, autonomic function,
CC       hormonal balance and the regulation of body fluids, is also
CC       suggested. A modulation effect on luteinizing hormone-releasing
CC       hormone (LHRH) secretion also suggests a more minor contribution
CC       to the regulation of reproductive function. Orexin-A binds to both
CC       OX1R and OX2R with a high affinity, whereas orexin-B binds only to
CC       OX2R with a similar high affinity.
CC   -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum. Note=Associated
CC       with perikaryal rough endoplasmic reticulum as well as cytoplasmic
CC       large granular vesicles at synapses.
CC   -!- TISSUE SPECIFICITY: Produced by a small group of neurons
CC       restricted to the lateral and posterior hypothalamus and
CC       perifornical areas. Positive neurons project widely throughout the
CC       entire neuroaxis. Particularly abundant projections in the
CC       cerebral cortex, olfactory bulb, hippocampus, amygdala, septum,
CC       diagonal band of Broca, bed nucleus of the stria terminalis,
CC       thalamus, anterior and posterior hypothalamus, midbrain,
CC       brainstem, and spinal cord. Immunoreactivity reported in the
CC       enteric nervous system and pancreas. In small amount, also
CC       detected in the testis.
CC   -!- DEVELOPMENTAL STAGE: Detected as early as embryonic day 18, but
CC       expression increased dramatically after the third postnatal week.
CC   -!- INDUCTION: By nutritional state, up-regulated by fasting, fluid
CC       deprivation and insulin-induced hypoglycemia. Orexin-A
CC       immunoreactivity varies diurnally and peaks during the dark phase,
CC       in the pons and the location of locus coeruleus.
CC   -!- PTM: Specific enzymatic cleavages at paired basic residues yield
CC       the different active peptides.
CC   -!- MASS SPECTROMETRY: Mass=3558.7; Mass_error=0.1; Method=MALDI;
CC       Range=33-65; Source=PubMed:9491897;
CC   -!- SIMILARITY: Belongs to the orexin family.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Qui dort dine - Issue
CC       15 of October 2001;
CC       URL="http://www.expasy.org/spotlight/back_issues/sptlt015.shtml";
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DR   EMBL; AF041241; AAC40039.1; -; mRNA.
DR   EMBL; AF019565; AAC02933.1; -; mRNA.
DR   IPI; IPI00196788; -.
DR   RefSeq; NP_037311.1; -.
DR   UniGene; Rn.7628; -.
DR   Ensembl; ENSRNOG00000018892; Rattus norvegicus.
DR   GeneID; 25723; -.
DR   KEGG; rno:25723; -.
DR   RGD; 2786; Hcrt.
DR   HOVERGEN; O55232; -.
DR   OMA; O55232; PCPGRRC.
DR   NextBio; 607825; -.
DR   ArrayExpress; O55232; -.
DR   GermOnline; ENSRNOG00000018892; Rattus norvegicus.
DR   GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0030141; C:secretory granule; IDA:RGD.
DR   GO; GO:0005184; F:neuropeptide hormone activity; IDA:RGD.
DR   GO; GO:0031771; F:type 1 hypocretin receptor binding; IDA:RGD.
DR   GO; GO:0031772; F:type 2 hypocretin receptor binding; IDA:RGD.
DR   GO; GO:0007200; P:activation of phospholipase C activity by G...; IMP:RGD.
DR   GO; GO:0007205; P:activation of protein kinase C activity by ...; IMP:RGD.
DR   GO; GO:0001662; P:behavioral fear response; NAS:RGD.
DR   GO; GO:0042755; P:eating behavior; IDA:RGD.
DR   GO; GO:0007204; P:elevation of cytosolic calcium ion concentr...; IDA:RGD.
DR   GO; GO:0008156; P:negative regulation of DNA replication; IDA:RGD.
DR   GO; GO:0043267; P:negative regulation of potassium ion transport; IDA:RGD.
DR   GO; GO:0051970; P:negative regulation of transmission of nerv...; IDA:RGD.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:RGD.
DR   GO; GO:0051971; P:positive regulation of transmission of nerv...; IDA:RGD.
DR   GO; GO:0060079; P:regulation of excitatory postsynaptic membr...; IDA:RGD.
DR   GO; GO:0046928; P:regulation of neurotransmitter secretion; IDA:RGD.
DR   InterPro; IPR001704; Orexin.
DR   PANTHER; PTHR15173; Orexin; 1.
DR   Pfam; PF02072; Orexin; 1.
DR   PRINTS; PR01091; OREXINPP.
PE   1: Evidence at protein level;
KW   Amidation; Cleavage on pair of basic residues;
KW   Direct protein sequencing; Disulfide bond; Endoplasmic reticulum;
KW   Neuropeptide; Pyrrolidone carboxylic acid; Signal.
FT   SIGNAL        1     32
FT   PEPTIDE      33     65       Orexin-A.
FT                                /FTId=PRO_0000020270.
FT   PEPTIDE      69     96       Orexin-B.
FT                                /FTId=PRO_0000020271.
FT   PROPEP       97    130
FT                                /FTId=PRO_0000020272.
FT   MOD_RES      33     33       Pyrrolidone carboxylic acid.
FT   MOD_RES      65     65       Leucine amide.
FT   MOD_RES      96     96       Methionine amide.
FT   DISULFID     38     44
FT   DISULFID     39     46
SQ   SEQUENCE   130 AA;  13645 MW;  00CAB259EDF2A404 CRC64;
     MNLPSTKVPW AAVTLLLLLL LPPALLSLGV DAQPLPDCCR QKTCSCRLYE LLHGAGNHAA
     GILTLGKRRP GPPGLQGRLQ RLLQANGNHA AGILTMGRRA GAELEPYPCP GRRCPTATAT
     ALAPRGGSRV
//