O43612 (OREX_HUMAN)
Reviewed,
UniProtKB/Swiss-Prot
Last modified
August 10, 2010.
Version 93.
History...
Names and origin
| Protein names | Recommended name: Orexin Alternative name(s): Hypocretin Short name=Hcrt Cleaved into the following 2 chains:
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| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 131 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. 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 junction › synapse 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 | Defects in HCRT are a cause of narcolepsy [MIM:161400]. Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as 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 associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. |
| Sequence similarities | Belongs to the orexin family. |
Ontologies
| Keywords | |
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| Cellular component | Cell junction Cytoplasmic vesicle Endoplasmic reticulum Synapse |
| Disease | Disease mutation |
| Domain | Signal |
| Molecular function | Neuropeptide |
| PTM | Amidation Cleavage on pair of basic residues Disulfide bond Pyrrolidone carboxylic acid |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | neuropeptide signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cell junction Inferred from electronic annotation. Source: UniProtKB-KW rough endoplasmic reticulumInferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicleTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||
Molecule processing | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 33 | 33 | By similarity | ||||||||||||||||||
| Peptide | 34 – 66 | 33 | Orexin-A | PRO_0000020261 | |||||||||||||||||
| Peptide | 70 – 97 | 28 | Orexin-B | PRO_0000020262 | |||||||||||||||||
| Propeptide | 98 – 131 | 34 | PRO_0000020263 | ||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||
| Modified residue | 34 | 1 | Pyrrolidone carboxylic acid By similarity | ||||||||||||||||||
| Modified residue | 66 | 1 | Leucine amide By similarity | ||||||||||||||||||
| Modified residue | 97 | 1 | Methionine amide By similarity | ||||||||||||||||||
| Disulfide bond | 39 ↔ 45 | Ref.6 Ref.8 | |||||||||||||||||||
| Disulfide bond | 40 ↔ 47 | Ref.6 Ref.8 | |||||||||||||||||||
Natural variations | |||||||||||||||||||||
| Natural variant | 16 | 1 | L → R in narcolepsy; early-onset; impaired trafficking and processing. Ref.9 | VAR_011633 | |||||||||||||||||
Secondary structure | |||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||
| Turn | 40 – 42 | 3 | |||||||||||||||||||
| Beta strand | 43 – 45 | 3 | |||||||||||||||||||
| Helix | 47 – 54 | 8 | |||||||||||||||||||
| Helix | 58 – 64 | 7 | |||||||||||||||||||
| Helix | 76 – 86 | 11 | |||||||||||||||||||
| Turn | 87 – 89 | 3 | |||||||||||||||||||
| Helix | 91 – 95 | 5 | |||||||||||||||||||
Sequences
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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. Yanagisawa M.Cell 92:573-585(1998) [PubMed: 9491897] [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: 10364220] [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: 10583376] [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: 11340621] [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: 11283317] [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: 15479620] [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: 14769912] [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: 16429482] [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. Mignot E.Nat. Med. 6:991-997(2000) [PubMed: 10973318] [Abstract] Cited for: CHARACTERIZATION OF VARIANT NARCOLEPSY ARG-16. |
| + | Additional computationally mapped references. |
Web resources
| Protein Spotlight Qui dort dine - Issue 15 of October 2001 |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||
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| EMBL GenBank DDBJ | AF041240 mRNA. Translation: AAC39600.1. AF118885 Genomic DNA. Translation: AAD24459.1. | ||||||||||||||||||||||||||||||
| IPI | IPI00013373. | ||||||||||||||||||||||||||||||
| RefSeq | NP_001515.1. | ||||||||||||||||||||||||||||||
| UniGene | Hs.158348. | ||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | O43612. | ||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||
| STRING | O43612. | ||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||
| PRIDE | O43612. | ||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||
| Ensembl | ENST00000293330; ENSP00000293330; ENSG00000161610; Homo sapiens. [Genome view] | ||||||||||||||||||||||||||||||
| GeneID | 3060. | ||||||||||||||||||||||||||||||
| KEGG | hsa:3060. | ||||||||||||||||||||||||||||||
| UCSC | uc002hzc.1. human. | ||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||
| CTD | 3060. | ||||||||||||||||||||||||||||||
| GeneCards | GC17M040337. | ||||||||||||||||||||||||||||||
| HGNC | HGNC:4847. HCRT. | ||||||||||||||||||||||||||||||
| HPA | CAB004758. | ||||||||||||||||||||||||||||||
| MIM | 161400. phenotype. 602358. gene. | ||||||||||||||||||||||||||||||
| Orphanet | 2073. Narcolepsy-cataplexy. | ||||||||||||||||||||||||||||||
| PharmGKB | PA29221. | ||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||
| eggNOG | prNOG21317. | ||||||||||||||||||||||||||||||
| HOGENOM | HBG279250. | ||||||||||||||||||||||||||||||
| HOVERGEN | HBG000256. | ||||||||||||||||||||||||||||||
| InParanoid | O43612. | ||||||||||||||||||||||||||||||
| OMA | PCPGRRC. | ||||||||||||||||||||||||||||||
| OrthoDB | EOG96X1TV. | ||||||||||||||||||||||||||||||
| PhylomeDB | O43612. | ||||||||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||||||||
| Reactome | REACT_14797. Signaling by GPCR. | ||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||
| ArrayExpress | O43612. | ||||||||||||||||||||||||||||||
| Bgee | O43612. | ||||||||||||||||||||||||||||||
| CleanEx | HS_HCRT. HS_PPOX. | ||||||||||||||||||||||||||||||
| Genevestigator | O43612. | ||||||||||||||||||||||||||||||
| GermOnline | ENSG00000161610. Homo sapiens. | ||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||
| InterPro | IPR001704. Orexin. [Graphical view] | ||||||||||||||||||||||||||||||
| PANTHER | PTHR15173. Orexin. 1 hit. | ||||||||||||||||||||||||||||||
| Pfam | PF02072. Orexin. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||
| PIRSF | PIRSF037824. Orexin. 1 hit. | ||||||||||||||||||||||||||||||
| PRINTS | PR01091. OREXINPP. | ||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||||||||
| NextBio | 12107. | ||||||||||||||||||||||||||||||
| PMAP-CutDB | O43612. | ||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||
Entry information
| Entry name | OREX_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O43612 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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
| Human chromosome 17 Human chromosome 17: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Protein Spotlight Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


