Property Summary

NCBI Gene PubMed Count 61
PubMed Score 138.33
PubTator Score 70.97

Knowledge Summary

Patent (3,259)

Expression

MLP Assay (9)

AID Type Active / Inconclusive / Inactive Description
434989 screening 1389 / 0 / 324747 Fluorescence-based cell-based primary high throughput screening assay to identify antagonists of the orexin 1 receptor (OX1R; HCRTR1)
435008 summary 0 / 0 / 0 Summary of the probe development effort to identify antagonists of the orexin 1 receptor (OX1R; HCRTR1)
485270 screening 5750 / 0 / 320386 FRET-based cell-based primary high throughput screening assay to identify antagonists of the orexin 1 receptor (OX1R; HCRTR1)
492963 screening 421 / 0 / 674 Fluorescence-based cell-based high throughput confirmation assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)
492964 screening 883 / 0 / 924 Homogeneous Time Resolved Fluorescence (HTRF)-based cell-based high throughput confirmation assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)
504699 confirmatory 161 / 0 / 86 Fluorescence-based cell-based high throughput dose response assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)
504701 confirmatory 228 / 0 / 19 Homogeneous Time Resolved Fluorescence (HTRF)-based cell-based high throughput dose response assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)
624409 confirmatory 10 / 0 / 18 Late stage assay for the probe development effort for antagonists of the orexin 1 receptor (OX1R; HCRTR1): Fluorescence-based cell-based dose response assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)
624410 confirmatory 25 / 0 / 3 Late stage assay for the probe development effort for antagonists of the orexin 1 receptor (OX1R; HCRTR1): Homogeneous Time Resolved Fluorescence (HTRF)-based cell-based dose response assay for antagonists of the orexin 1 receptor (OX1R; HCRTR1)

Gene RIF (52)

PMID Text
26950369 This study determined structures of OX1R bound to the OX1R-selective antagonist SB-674042 and the dual antagonist suvorexant at 2.8-A and 2.75-A resolution.
26555080 Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is highly unlikely to be caused by mutations in the exons of the HCRTR1 gene.
26459696 the orexinA/OX1 receptor axis has a significant pro-survival function in adrenal cells.
25957175 Results from homology and docking modeling show two alternative binding modes for orexin-A into orexin 1 receptor in concordance with what is known of G protein coupled receptors activation in general and the mutational data.
25866368 OX1R and KOR heterodimerize, and this heterodimer associates with Galphas, leading to increased protein kinase A (PKA) signaling pathway activity, including upregulation of intracellular cAMP levels.
25857454 OX1R signaling can attenuate KOR-mediated reduction of cellular cAMP levels while enhancing KOR-mediated beta-arrestin recruitment and p38 activation.
25677777 Data suggest that interaction between the nociceptin/nociceptin receptor system and the orexin/orexin receptor system in neurons of the hypothalamus positively and negatively modulate complex and integrated responses to stress. [REVIEW]
25515760 Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway.
25212464 Decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging.
25132134 Orexin receptor binding was strongly dependent on the extracellular Ca(2+) concentration.
24969517 No significant differences were found in the distribution of either genotypic or allelic frequencies between Alzheimer's disease cases and controls in the HCRTR1 polymorphisms.
24910418 The present data indicate that OX1R-driven apoptosis is overexpressed in androgeno-independent prostate cancer exhibiting a neuroendocrine differentiation opening a gate for novel therapies for these aggressive cancers which are incurable until now.
24530395 Both orexin receptor subtypes, OX1R and OX2R, and CB1 cannabinoid receptors are capable of forming constitutive homo- and heteromeric complexes.
24333629 Orexins modifiy orexin receptor gene expression and gonadotropin release from the anterior pituitary gland.
24268496 DQ B1 but not HLA-DR typing, TNF-alpha levels, HCRTR1 and HCRTR2 were higher in narcolepsy-cataplexy/schizophrenia patients.
23034387 [review] Native orexin peptides consist of receptor agonists, orexin-A (33 amino acids) and orexin-B (28 amino acids) (aka hypocretin-1 and hypocretin-2).
22550093 Orexin receptors generate potent endocannabinoid signals in addition to arachidonic acid signals, which may explain the proposed orexin-cannabinoid interactions.
22389503 Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
22028875 Dynlt1 modulates orexin signaling by regulating OX1R
21908614 Heteromultimerization of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both protomers are regulated by orexin A.
21666548 The Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls, were analyzed.
21510948 Results show that the N-terminal regions of orexin receptor are most important, and the exchange of the area from the C-terminal part of the transmembrane helix 2 to the transmembrane helix 4 is enough to lead to a change of the receptor's ligand profile.
21378163 analysis of orexin receptor 1 and 2 -arrestin-ubiquitin complexes
21344296 HCRTR1 gene could represent a genetic susceptibility factor for migraine without aura; the hypocretin system may have a role in the pathophysiology of migraine.
21318258 decreased ventilatory responses to hypoxia in human narcolepsy-cataplexy is in relation to HLA-DQB1*0602 status, not hypocretin deficiency
21071097 Data show that the HCRTR1 gene or a linked locus may modulate the risk for Major Mood Disorders and supports recent studies suggesting an involvement of hypocretin neurotransmitter system in affective disorders.
21071097 Observational study of gene-disease association. (HuGE Navigator)
20728215 In differentiated IMR-32 neuroblastoma cells orexin/hypocretin and bradykinin receptors activate TRPC3/6 channels.
20621130 Data demonstrate the functional role of protein kinase D1 and protein kinase D3 in modulating physiological responses to Ox1R activation.
20468064 Observational study of gene-disease association. (HuGE Navigator)
20398908 Observational study of gene-disease association. (HuGE Navigator)
20002100 OX1 orexin receptor activation results in robust arachidonic acid release.
19661287 It was shown here that another motif, immunoreceptor tyrosine-based switch motif, is present in orexin receptor-1 (OX1R) and is mandatory for OX1R-mediated apoptosis.
19464259 OX1R are able to activate TRPC(3)-channel-dependent oscillatory responses independently of store discharge.
19118115 Induction of intracellular calcium signaling in isolated duodenal enterocytes is mediated primarily by OX1R receptors
19086053 Observational study of gene-disease association. (HuGE Navigator)
19058789 Observational study of gene-disease association. (HuGE Navigator)
18714784 Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases.
18450961 Orexin effects on StAR were primarily, but not exclusively, acting through the orexin receptor type 1.
18198212 orexin-induced apoptosis is driven by an immunoreceptor tyrosine-based inhibitory motif (ITIM) present in the OX1R and is mediated by SHP-2 phosphatase recruitment via a mechanism that requires Gq protein but is independent of phospholipase C activation.
17999203 Observational study of gene-disease association. (HuGE Navigator)
17999203 Results support the hypothesis that the HCRTR1 Ile408Val polymorphism may confer susceptibility to polydipsia in schizophrenia.
17089135 This is the first demonstration of loss of Hcrt/Orx neurons in MSA, which is consistent with a system degeneration of neurons involved in homeostatic function, including sleep and autonomic regulation, in this disorder.
16282319 OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase
16157481 Orexins act exclusively through OX1-receptors coupled to the adenylate cyclase/protein kinase A-dependent signaling cascade.
15978554 Observational study of gene-disease association. (HuGE Navigator)
15978554 Our preliminary data suggest that mutation hcrtr1 might have an increased susceptibility to polydipsia through an undetermined mechanism.
15797953 All adrenal corttex adenomas expressed OX1-R and OX2-R mRNAs, and real-time PCR showed that the expression of both receptors was up-regulated in adenomas
15611118 OX(1) receptors stimulate adenylyl cyclase via a low potency G(s) coupling and a high potency phospholipase C --> PKC coupling.
15070969 both OX1R and OX2R are expressed in the testis, epididymis, penis, and seminal vesicle
12690115 evidence that CB1 is able to potentiate an orexigenic receptor, OX1R
11856342 The SK-N-MC cell line expresses an orexin binding site different from recombinant orexin 1-type receptor.

AA Sequence

MEPSATPGAQMGVPPGSREPSPVPPDYEDEFLRYLWRDYLYPKQYEWVLIAAYVAVFVVALVGNTLVCLA      1 - 70
VWRNHHMRTVTNYFIVNLSLADVLVTAICLPASLLVDITESWLFGHALCKVIPYLQAVSVSVAVLTLSFI     71 - 140
ALDRWYAICHPLLFKSTARRARGSILGIWAVSLAIMVPQAAVMECSSVLPELANRTRLFSVCDERWADDL    141 - 210
YPKIYHSCFFIVTYLAPLGLMAMAYFQIFRKLWGRQIPGTTSALVRNWKRPSDQLGDLEQGLSGEPQPRA    211 - 280
RAFLAEVKQMRARRKTAKMLMVVLLVFALCYLPISVLNVLKRVFGMFRQASDREAVYACFTFSHWLVYAN    281 - 350
SAANPIIYNFLSGKFREQFKAAFSCCLPGLGPCGSLKAPSPRSSASHKSLSLQSRCSISKISEHVVLTSV    351 - 420
TTVLP                                                                     421 - 425
//

Text Mined References (64)

PMID Year Title
26950369 2016 Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors.
26555080 2016 Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD.
26459696 2015 Orexin-A regulates cell apoptosis in human H295R adrenocortical cells via orexin receptor type 1 through the AKT signaling pathway.
25957175 2015 Modeling of the OX1R-orexin-A complex suggests two alternative binding modes.
25866368 2015 Heterodimerization of human orexin receptor 1 and kappa opioid receptor promotes protein kinase A/cAMP-response element binding protein signaling via a G?s-mediated mechanism.
25857454 2015 The orexin 1 receptor modulates kappa opioid receptor function via a JNK-dependent mechanism.
25677777 2015 The neuronal circuit between nociceptin/orphanin FQ and hypocretins/orexins coordinately modulates stress-induced analgesia and anxiety-related behavior.
25515760 2015 Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway.
25212464 2015 Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus.
25132134 2014 Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery.
24969517 2014 Is HCRTR2 a genetic risk factor for Alzheimer's disease?
24910418 2014 The orexin type 1 receptor is overexpressed in advanced prostate cancer with a neuroendocrine differentiation, and mediates apoptosis.
24530395 2014 Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors.
24333629 2014 Orexin A and B in vitro modify orexins receptors expression and gonadotropins secretion of anterior pituitary cells of proestrous rats.
24268496 2014 Narcolepsy-cataplexy and schizophrenia in adolescents.
23034387 2013 Physiology of the orexinergic/hypocretinergic system: a revisit in 2012.
22550093 2012 OX1 orexin/hypocretin receptor signaling through arachidonic acid and endocannabinoid release.
22389503 2012 Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
22028875 2011 Dynein light chain Tctex-type 1 modulates orexin signaling through its interaction with orexin 1 receptor.
21908614 2011 Heteromultimerization of cannabinoid CB(1) receptor and orexin OX(1) receptor generates a unique complex in which both protomers are regulated by orexin A.
21666548 2011 Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene.
21510948 2011 Orexin/hypocretin receptor chimaeras reveal structural features important for orexin peptide distinction.
21378163 2011 Temporal profiling of orexin receptor-arrestin-ubiquitin complexes reveals differences between receptor subtypes.
21344296 2011 Evidence for an association between migraine and the hypocretin receptor 1 gene.
21318258 2012 Respiratory regulation in narcolepsy.
21071097 2011 Association between major mood disorders and the hypocretin receptor 1 gene.
20728215 Selective interference with TRPC3/6 channels disrupts OX1 receptor signalling via NCX and reveals a distinct calcium influx pathway.
20621130 2010 A role for PKD1 and PKD3 activation in modulation of calcium oscillations induced by orexin receptor 1 stimulation.
20468064 2010 Association study of 182 candidate genes in anorexia nervosa.
20398908 2010 Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients.
20002100 2010 Arachidonic acid release mediated by OX1 orexin receptors.
19661287 2009 Discovery of a functional immunoreceptor tyrosine-based switch motif in a 7-transmembrane-spanning receptor: role in the orexin receptor OX1R-driven apoptosis.
19464259 2009 Involvement of TRPC3 channels in calcium oscillations mediated by OX(1) orexin receptors.
19118115 2009 Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
19058789 2009 A common variant in DRD3 receptor is associated with autism spectrum disorder.
18714784 2008 Hypocretin receptor expression in canine and murine narcolepsy models and in hypocretin-ligand deficient human narcolepsy.
18450961 2008 Orexins stimulate steroidogenic acute regulatory protein expression through multiple signaling pathways in human adrenal H295R cells.
18198212 2008 A hallmark of immunoreceptor, the tyrosine-based inhibitory motif ITIM, is present in the G protein-coupled receptor OX1R for orexins and drives apoptosis: a novel mechanism.
17999203 2007 The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia.
17089135 2007 Involvement of hypocretin neurons in multiple system atrophy.
16754659 2006 Stable association between G alpha(q) and phospholipase C beta 1 in living cells.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16282319 2006 G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and -independent cell death through p38 mitogen-/stress-activated protein kinase.
16157481 2005 Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor.
15978554 2005 Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects.
15797953 2005 Preproorexin and orexin receptors are expressed in cortisol-secreting adrenocortical adenomas, and orexins stimulate in vitro cortisol secretion and growth of tumor cells.
15611118 2005 OX1 orexin receptors couple to adenylyl cyclase regulation via multiple mechanisms.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15070969 2004 Expression of human prepro-orexin and signaling characteristics of orexin receptors in the male reproductive system.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12690115 2003 Hypersensitization of the Orexin 1 receptor by the CB1 receptor: evidence for cross-talk blocked by the specific CB1 antagonist, SR141716.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11856342 2002 The SK-N-MC cell line expresses an orexin binding site different from recombinant orexin 1-type receptor.
11723285 2001 Polymorphisms in hypocretin/orexin pathway genes and narcolepsy.
11443222 2001 Cellular localization of orexin receptors in human pituitary.
11340621 2001 Hypocretin/orexin, sleep and narcolepsy.
11283317 2001 To eat or to sleep? Orexin in the regulation of feeding and wakefulness.
10973318 2000 A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.
9527442 1998 Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
9491897 1998 Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.
9491885 1998 Obesity and the hypothalamus: novel peptides for new pathways.
9419374 1998 The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.