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O43612 (OREX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Orexin
Alternative name(s):
Hypocretin
Short name=Hcrt

Cleaved into the following 2 chains:

  1. Orexin-A
    Alternative name(s):
    Hypocretin-1
    Short name=Hcrt1
  2. Orexin-B
    Alternative name(s):
    Hypocretin-2
    Short name=Hcrt2
Gene names
Name:HCRT
Synonyms:OX, PPORX, PPOX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length131 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. 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 junctionsynapse 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.

Post-translational modification

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

Involvement in disease

Narcolepsy 1 (NRCLP1) [MIM:161400]: Neurological 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.
Note: 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. Ref.9

Sequence similarities

Belongs to the orexin family.

Ontologies

Keywords
   Cellular componentCell junction
Cytoplasmic vesicle
Endoplasmic reticulum
Synapse
   DiseaseDisease mutation
   DomainSignal
   Molecular functionNeuropeptide
   PTMAmidation
Cleavage on pair of basic residues
Disulfide bond
Pyrrolidone carboxylic acid
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processeating behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of transmission of nerve impulse

Inferred from electronic annotation. Source: Ensembl

neuropeptide signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipase C-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of calcium ion transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of transmission of nerve impulse

Inferred from electronic annotation. Source: Ensembl

protein kinase C-activating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement PubMed 9419374. Source: ProtInc

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular region

Traceable author statement. Source: Reactome

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

rough endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

secretory granule

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle

Traceable author statement PubMed 9419374. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 By similarity
Peptide34 – 6633Orexin-A
PRO_0000020261
Peptide70 – 9728Orexin-B
PRO_0000020262
Propeptide98 – 13134
PRO_0000020263

Amino acid modifications

Modified residue341Pyrrolidone carboxylic acid By similarity
Modified residue661Leucine amide By similarity
Modified residue971Methionine amide By similarity
Disulfide bond39 ↔ 45 Ref.6 Ref.8
Disulfide bond40 ↔ 47 Ref.6 Ref.8

Natural variations

Natural variant161L → R in NRCLP1; early-onset; impaired trafficking and processing. Ref.9
VAR_011633

Secondary structure

............. 131
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43612 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 139D9C33E39E4EF1

FASTA13113,363
        10         20         30         40         50         60 
MNLPSTKVSW AAVTLLLLLL LLPPALLSSG AAAQPLPDCC RQKTCSCRLY ELLHGAGNHA 

        70         80         90        100        110        120 
AGILTLGKRR SGPPGLQGRL QRLLQASGNH AAGILTMGRR AGAEPAPRPC LGRRCSAPAA 

       130 
ASVAPGGQSG I 

« Hide

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. expand/collapse author list , Elshourbagy N.A., Bergsma D.J., Yanagisawa M.
Cell 92:573-585(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure and function of human prepro-orexin gene."
Sakurai T., Moriguchi T., Furuya K., Kajiwara N., Nakamura T., Yanagisawa M., Goto K.
J. Biol. Chem. 274:17771-17776(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B."
Lee J.-H., Bang E., Chae K.-J., Kim J.-Y., Lee D.W., Lee W.
Eur. J. Biochem. 266:831-839(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 70-97.
[4]"Hypocretin/orexin, sleep and narcolepsy."
Hungs M., Mignot E.
Bioessays 23:397-408(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[5]"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] [Europe PMC] [Abstract]
Cited for: REVIEW.
[6]"Solution structure of human orexin-A: regulator of appetite and wakefulness."
Kim H.Y., Hong E., Kim J.I., Lee W.
J. Biochem. Mol. Biol. 37:565-573(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 34-66, DISULFIDE BONDS.
[7]"Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy."
Siebold C., Hansen B.E., Wyer J.R., Harlos K., Esnouf R.E., Svejgaard A., Bell J.I., Strominger J.L., Jones E.Y., Fugger L.
Proc. Natl. Acad. Sci. U.S.A. 101:1999-2004(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-12 IN COMPLEX OF HLA-DQA1/HLA-DQB1 HETERODIMER (HLA-DQ0602).
[8]"Orexin-A is composed of a highly conserved C-terminal and a specific, hydrophilic N-terminal region, revealing the structural basis of specific recognition by the orexin-1 receptor."
Takai T., Takaya T., Nakano M., Akutsu H., Nakagawa A., Aimoto S., Nagai K., Ikegami T.
J. Pept. Sci. 12:443-454(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 35-66, DISULFIDE BONDS.
[9]"A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains."
Peyron C., Faraco J., Rogers W., Ripley B., Overeem S., Charnay Y., Nevsimalova S., Aldrich M., Reynolds D., Albin R., Li R., Hungs M., Pedrazzoli M., Padigaru M., Kucherlapati M., Fan J., Maki R., Lammers G.J. expand/collapse author list , Bouras C., Kucherlapati R., Nishino S., Mignot E.
Nat. Med. 6:991-997(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT NRCLP1 ARG-16.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Qui dort dine - Issue 15 of October 2001

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF041240 mRNA. Translation: AAC39600.1.
AF118885 Genomic DNA. Translation: AAD24459.1.
CCDSCCDS11421.1.
RefSeqNP_001515.1. NM_001524.1.
UniGeneHs.158348.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CQ0NMR-A71-97[»]
1R02NMR-A34-66[»]
1UVQX-ray1.80C1-12[»]
1WSONMR-A34-66[»]
ProteinModelPortalO43612.
SMRO43612. Positions 34-66, 71-97.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109310. 1 interaction.
IntActO43612. 1 interaction.
STRING9606.ENSP00000293330.

Proteomic databases

MaxQBO43612.
PaxDbO43612.
PRIDEO43612.

Protocols and materials databases

DNASU3060.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000293330; ENSP00000293330; ENSG00000161610.
GeneID3060.
KEGGhsa:3060.
UCSCuc002hzc.1. human.

Organism-specific databases

CTD3060.
GeneCardsGC17M040337.
HGNCHGNC:4847. HCRT.
HPACAB004758.
MIM161400. phenotype.
602358. gene.
neXtProtNX_O43612.
Orphanet83465. Narcolepsy without cataplexy.
2073. Narcolepsy-cataplexy.
PharmGKBPA29221.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70925.
HOGENOMHOG000230990.
HOVERGENHBG000256.
InParanoidO43612.
KOK05246.
OMASECCRQP.
OrthoDBEOG7XSTHD.
PhylomeDBO43612.
TreeFamTF330756.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeO43612.
CleanExHS_HCRT.
HS_PPOX.
GenevestigatorO43612.

Family and domain databases

InterProIPR001704. Orexin.
[Graphical view]
PANTHERPTHR15173. PTHR15173. 1 hit.
PfamPF02072. Orexin. 1 hit.
[Graphical view]
PIRSFPIRSF037824. Orexin. 1 hit.
PRINTSPR01091. OREXINPP.
ProtoNetSearch...

Other

EvolutionaryTraceO43612.
GenomeRNAi3060.
NextBio12107.
PMAP-CutDBO43612.
PROO43612.
SOURCESearch...

Entry information

Entry nameOREX_HUMAN
AccessionPrimary (citable) accession number: O43612
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM