Hypocretin (orexin) receptor 1

Orexin receptor type 1 (Ox1R or OX₁), also known as hypocretin receptor type 1 (HcrtR1), is a protein that in humans is encoded by the HCRTR1 gene.

HCRTR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ZJ8, 4ZJC
Identifiers
Aliases	HCRTR1, OX1R, Hypocretin (orexin) receptor 1, hypocretin receptor 1, ORXR1, OXR1
External IDs	OMIM: 602392 MGI: 2385650 HomoloGene: 37492 GeneCards: HCRTR1
Gene location (Human) Chr. Chromosome 1 (human) Band 1p35.2 Start 31,617,686 bp End 31,632,518 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4|4 D2.2 Start 130,024,010 bp End 130,033,152 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in superior frontal gyrus right lobe of thyroid gland placenta prefrontal cortex left lobe of thyroid gland left ventricle skeletal muscle tissue hypothalamus muscle of leg gastrocnemius muscle Top expressed in substantia nigra spinal ganglia visual cortex dorsal tegmental nucleus superior frontal gyrus mirror ventral tegmental area cerebellar cortex urinary bladder neural tube More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptide hormone binding peptide binding G protein-coupled receptor activity signal transducer activity orexin receptor activity Cellular component integral component of membrane plasma membrane membrane integral component of plasma membrane Biological process cellular response to hormone stimulus regulation of circadian sleep/wake cycle, sleep signal transduction response to peptide chemical synaptic transmission regulation of cytosolic calcium ion concentration positive regulation of ERK1 and ERK2 cascade neuropeptide signaling pathway feeding behavior G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3061 230777 Ensembl ENSG00000121764 ENSMUSG00000028778 UniProt O43613 P58307 RefSeq (mRNA) NM_001525 NM_001163027 NM_198959 NM_001305392 NM_001357258 RefSeq (protein) NP_001516 NP_001156499 NP_001292321 NP_945197 NP_001344187 Location (UCSC) Chr 1: 31.62 – 31.63 Mb Chr 4: 130.02 – 130.03 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

The orexin 1 receptor (OX₁), is a G-protein coupled receptor that is heavily expressed in projections from the lateral hypothalamus and is involved in the regulation of feeding behaviour. OX₁ selectively binds the orexin-A neuropeptide. It shares 64% identity with OX₂.

Ligands

Agonists

• Orexin-A

Antagonists

Further information: Orexin antagonist

• RTIOX-276 - Selective OX₁ antagonist
• ACT-335827 - Selective OX₁ antagonist
• Almorexant - Dual OX₁ and OX₂ antagonist
• Lemborexant - Dual OX₁ and OX₂ antagonist
• Nemorexant - Dual OX₁ and OX₂ antagonist
• SB-334,867 - Selective OX₁ antagonist
• SB-408,124 - Selective OX₁ antagonist
• SB-649,868 - Dual OX₁ and OX₂ antagonist
• Suvorexant - Dual OX₁ and OX₂ antagonist

See also

• Orexin receptor

External links

• "Orexin Receptors: OX₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Further reading

• Flier JS, Maratos-Flier E (Feb 1998). "Obesity and the hypothalamus: novel peptides for new pathways". Cell. 92 (4): 437–40. doi:10.1016/S0092-8674(00)80937-X. PMID 9491885. S2CID 14768585.
• Willie JT, Chemelli RM, Sinton CM, Yanagisawa M (2001). "To eat or to sleep? Orexin in the regulation of feeding and wakefulness". Annual Review of Neuroscience. 24: 429–58. doi:10.1146/annurev.neuro.24.1.429. PMID 11283317.
• Hungs M, Mignot E (May 2001). "Hypocretin/orexin, sleep and narcolepsy". BioEssays. 23 (5): 397–408. doi:10.1002/bies.1058. PMID 11340621. S2CID 541650.
• de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (Jan 1998). "The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity". Proceedings of the National Academy of Sciences of the United States of America. 95 (1): 322–7. Bibcode:1998PNAS...95..322D. doi:10.1073/pnas.95.1.322. PMC 18213. PMID 9419374.
• Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (Feb 1998). "Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior". Cell. 92 (4): 573–85. doi:10.1016/S0092-8674(00)80949-6. PMID 9491897. S2CID 16294729.
• Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richarson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (Mar 1998). "Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior". Cell. 92 (5): 1 page following 696. doi:10.1016/S0092-8674(02)09256-5. PMID 9527442.
• 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 GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E (Sep 2000). "A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains". Nature Medicine. 6 (9): 991–7. doi:10.1038/79690. PMID 10973318. S2CID 18076282.
• Blanco M, López M, GarcIa-Caballero T, Gallego R, Morel G, SeñarIs R, Casanueva F, Diéguez C, Beiras A (Jul 2001). "Cellular localization of orexin receptors in human pituitary". The Journal of Clinical Endocrinology and Metabolism. 86 (7): 1616–9. doi:10.1210/jcem.86.7.7433. PMID 11443222.
• Olafsdóttir BR, Rye DB, Scammell TE, Matheson JK, Stefánsson K, Gulcher JR (Nov 2001). "Polymorphisms in hypocretin/orexin pathway genes and narcolepsy". Neurology. 57 (10): 1896–9. doi:10.1212/wnl.57.10.1896. PMID 11723285. S2CID 38597998.
• Wieland HA, Söll RM, Doods HN, Stenkamp D, Hurnaus R, Lämmle B, Beck-Sickinger AG (Feb 2002). "The SK-N-MC cell line expresses an orexin binding site different from recombinant orexin 1-type receptor". European Journal of Biochemistry. 269 (4): 1128–35. doi:10.1046/j.0014-2956.2001.02739.x. PMID 11856342.
• Hilairet S, Bouaboula M, Carrière D, Le Fur G, Casellas P (Jun 2003). "Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716". The Journal of Biological Chemistry. 278 (26): 23731–7. doi:10.1074/jbc.M212369200. PMID 12690115.
• Karteris E, Chen J, Randeva HS (Apr 2004). "Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system". The Journal of Clinical Endocrinology and Metabolism. 89 (4): 1957–62. doi:10.1210/jc.2003-031778. PMID 15070969.
• Holmqvist T, Johansson L, Ostman M, Ammoun S, Akerman KE, Kukkonen JP (Feb 2005). "OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms". The Journal of Biological Chemistry. 280 (8): 6570–9. doi:10.1074/jbc.M407397200. PMID 15611118.
• Spinazzi R, Rucinski M, Neri G, Malendowicz LK, Nussdorfer GG (Jun 2005). "Preproorexin and orexin receptors are expressed in cortisol-secreting adrenocortical adenomas, and orexins stimulate in vitro cortisol secretion and growth of tumor cells". The Journal of Clinical Endocrinology and Metabolism. 90 (6): 3544–9. doi:10.1210/jc.2004-2385. PMID 15797953.
• Meerabux J, Iwayama Y, Sakurai T, Ohba H, Toyota T, Yamada K, Nagata R, Irukayama-Tomobe Y, Shimizu H, Yoshitsugu K, Ohta K, Yoshikawa T (Sep 2005). "Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects". Biological Psychiatry. 58 (5): 401–7. doi:10.1016/j.biopsych.2005.04.015. PMID 15978554. S2CID 26813056.
• Ziolkowska A, Spinazzi R, Albertin G, Nowak M, Malendowicz LK, Tortorella C, Nussdorfer GG (Sep 2005). "Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor". The Journal of Steroid Biochemistry and Molecular Biology. 96 (5): 423–9. doi:10.1016/j.jsbmb.2005.05.003. PMID 16157481. S2CID 27293941.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.