Hypocretin (orexin) receptor 1

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
External IDs	OMIM: 602392 MGI: 2385650 HomoloGene: 37492 GeneCards: HCRTR1
Gene location (Human)
Chr.	Chromosome 1 (human)
End	31,632,518 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	130,139,359 bp
RNA expression pattern
	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
	3061
	230777
	ENSG00000121764
	ENSMUSG00000028778
	O43613
	P58307
	NM_001525
	NM_001163027; NM_198959; NM_001305392; NM_001357258
	NP_001516
	NP_001156499; NP_001292321; NP_945197; NP_001344187
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5]

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.^[5]

Ligands[]

Agonists[]

Orexin-A

Antagonists[]

RTIOX-276 - Selective OX₁ antagonist
ACT-335827 - Selective OX₁ antagonist
Almorexant - Dual OX₁ and OX₂ antagonist
Lemborexant - Dual OX₁ and OX₂ antagonist^[6]
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

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000121764 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028778 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: HCRTR1 hypocretin (orexin) receptor 1".
^ "Eisai Demonstrates Efficacy of Investigational Dual Orexin Receptor Antagonist E2006 in Sleep Initiation and Maintenance Data from Phase II Clinical Trial for Insomnia".

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" (PDF). 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/jc.86.7.3444. 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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000121764 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028778 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: HCRTR1 hypocretin (orexin) receptor 1".

[6] "Eisai Demonstrates Efficacy of Investigational Dual Orexin Receptor Antagonist E2006 in Sleep Initiation and Maintenance Data from Phase II Clinical Trial for Insomnia".

[1]

[2]

[3]

[4]

[5]

[6]

v t Orexin receptor modulators
OX₁	Agonists: Orexin (A, B) Antagonists: ACT-335827 ACT-462206 Almorexant Daridorexant Filorexant GSK-649868 (SB-649868) Lemborexant RTIOX-276 SB-334867 SB-408124 Suvorexant Vornorexant (ORN-0829, TS-142)
OX₂	Agonists: Danavorexton (TAK-925) Firazorexton Orexin (A, B) Suntinorexton TAK-994 Antagonists: ACT-335827 ACT-462206 Almorexant EMPA Filorexant GSK-649868 (SB-649868) JNJ-10397049 Lemborexant Seltorexant Suvorexant TCS-OX2-29 Vornorexant (ORN-0829, TS-142)