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OX2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 322

Nomenclature: OX2 receptor

Family: Orexin receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 444 6p12.1 HCRTR2 hypocretin receptor 2 61
Mouse 7 460 9q-D Hcrtr2 hypocretin (orexin) receptor 2 14,61
Rat 7 460 8q24 Hcrtr2 hypocretin receptor 2 61
Gene and Protein Information Comments
Splice variants of the mouse gene are reported, generating different protein isoforms. Isoform 2 lacks amino acids 444-460 of the carboxy terminal tail compared to canonical full lenghth isoform 1.
Previous and Unofficial Names Click here for help
hypocretin receptor 2 | orexin receptor type 2 | OX2R
Database Links Click here for help
Specialist databases
GPCRdb ox2r_human (Hs), ox2r_mouse (Mm), ox2r_rat (Rn)
Other databases
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Orexin Receptor 2 (OX2R) in Complex with G Protein and Natural Peptide-Agonist Orexin B (OxB)
PDB Id:  7L1U
Ligand:  orexin-B
Resolution:  3.2Å
Species:  Human
References:  28
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human OX2 orexin receptor bound to the insomnia drug Suvorexant
PDB Id:  4S0V
Ligand:  suvorexant
Resolution:  2.5Å
Species:  Human
References:  76
Image of receptor 3D structure from RCSB PDB
Description:  Orexin Receptor 2 (OX2R) in Complex with G Protein and Small-Molecule Agonist Compound 1
PDB Id:  7L1V
Ligand:  compound 1 [PMID: 33547286]
Resolution:  3.0Å
Species:  Human
References:  28
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structures of human orexin 2 receptor bound to the selective antagonist EMPA determined by serial femtosecond crystallography at SACLA
PDB Id:  5WS3
Ligand:  EMPA
Resolution:  2.3Å
Species:  Human
References:  66
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human OX2R bound to the insomnia drug lemborexant.
PDB Id:  7XRR
Ligand:  lemborexant
Resolution:  2.89Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Orexin-2 receptor in complex with HTL6641 at 2.61 A resolution
PDB Id:  6TPN
Ligand:  HTL6641
Resolution:  2.61Å
Species:  Human
References:  56
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Orexin-2 receptor in complex with suvorexant at 2.76 A resolution
PDB Id:  6TPJ
Ligand:  suvorexant
Resolution:  2.76Å
Species:  Human
References:  56
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the Orexin-2 receptor in complex with EMPA at 2.74 A resolution
PDB Id:  6TPG
Ligand:  EMPA
Resolution:  2.74Å
Species:  Human
References:  56
Natural/Endogenous Ligands Click here for help
orexin-A {Sp: Human, Mouse, Rat}
orexin-B {Sp: Human} , orexin-B {Sp: Mouse, Rat}
Potency order of endogenous ligands (Human)
orexin-A (HCRT, O43612) = orexin-B (HCRT, O43612)

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]T-516 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Agonist 7.3 pKd 78
pKd 7.3 (Kd 4.8x10-8 M) [78]
Description: Determined in a radioligand binding assay using membrane fractions from hOX2R-transfected Expi293F cells.
firazorexton Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.0 pKd 32
pKd 7.0 (Kd 1x10-7 M) [32]
Description: Dissocaition constant determined in a saturation binding assay
[Ala11, D-Leu15]orexin-B Peptide Primary target of this compound Click here for species-specific activity table Hs Full agonist 7.6 – 9.9 pEC50 4,53
pEC50 7.6 – 9.9 [4,53]
T-516 Small molecule or natural product Hs Full agonist 8.4 pEC50 78
pEC50 8.4 (EC50 4.3x10-9 M) [78]
Description: Determined in a calcium mobilization assay
compound 1 [PMID: 33547286] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.3 pEC50 28
pEC50 8.3 [28]
danavorexton Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 8.3 pEC50 78
pEC50 8.3 (EC50 5.5x10-9 M) [78]
Description: Measuring TAK-925-induced calcium mobilization in hOX2R/CHO-K1 cells
orexin-A {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.5 – 10.0 pEC50 2,24,26,34-35,50,61,64,68
pEC50 6.5 – 10.0 [2,24,26,34-35,50,61,64,68]
orexin-B {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.5 – 10.0 pEC50 2,24,26,50,61,64,68
pEC50 6.5 – 10.0 [2,24,26,50,61,64,68]
RTOXA-43 Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.6 pEC50
pEC50 7.6 (EC50 2.4x10-8 M)
Description: Determined in a Ca2+ response assay.
YNT-185 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Full agonist 7.6 pEC50 30,48
pEC50 7.6 (EC50 2.8x10-8 M) [30,48]
firazorexton Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.0 – 7.7 pEC50 32
pEC50 7.7 (EC50 1.9x10-8 M) [32]
Description: Determined in a calcoium mobilization assay
pEC50 7.4 (EC50 3.7x10-8 M) [32]
Description: Increase of IP1 release
pEC50 7.0 (EC50 1x10-7 M) [32]
Description: Increase of β-arrestin recruitment
(R)-YNT-3708 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.8 pEC50 29
pEC50 6.8 (EC50 1.68x10-7 M) [29]
Description: Determined in a calcium mobilization assay
Nag 26 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 5.2 – 7.8 pEC50 30,48,57
pEC50 5.2 – 7.8 (EC50 6.31x10-6 – 1.58x10-8 M) [30,48,57]
Agonist Comments
Efficacy and potency values for agonists are highly dependent on cell type, assay conditions and the readout. Agonist activity of firazorexton (TAK-994) has been demonstrated in ERK phosphorylation, CREB phosphorylation, and tuberomamillary nucleus neuron depolarization assays, with pEC50 values of 6.8, 7.4 and 7.7 respectively [32].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
filorexant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.7 pKB 13
pKB 9.7 [13]
SB-649868 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 9.7 pKB 13
pKB 9.7 [13]
filorexant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 9.6 pKB 13
pKB 9.6 [13]
SB-649868 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKB 13
pKB 9.6 [13]
suvorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.5 pKB 70
pKB 9.5 [70]
TCS 1102 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 – 9.7 pKB 6,57
pKB 8.8 – 9.7 [6,57]
suvorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 9.2 pKB 70
pKB 9.2 [70]
daridorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Clf Antagonist 9.2 pKB 58
pKB 9.2 [58]
almorexant Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.9 – 9.3 pKB 13,70
pKB 9.3 [70]
pKB 8.9 [13]
daridorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 – 9.1 pKB 56,70
pKB 8.9 – 9.1 [56,70]
almorexant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 pKB 13
pKB 8.9 [13]
SB-649868 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 8.8 pKB 13
pKB 8.8 [13]
seltorexant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 pKB 8
pKB 8.8 [8]
daridorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.8 pKB 70
pKB 8.8 [70]
ACT-462206 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.6 pKB 10
pKB 8.6 [10]
suvorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 8.3 pKB 70
pKB 8.3 [70]
almorexant Small molecule or natural product Click here for species-specific activity table Mm Antagonist 8.2 pKB 13
pKB 8.2 [13]
filorexant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 8.2 pKB 13
pKB 8.2 [13]
JNJ-10397049 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 – 8.3 pKB 44,69
pKB 8.3 [44]
pKB 7.7 [69]
seltorexant Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.0 pKB 8
pKB 8.0 [8]
SB-674042 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.9 pKB 41
pKB 6.9 [41]
SB-334867 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.3 pKB 42
pKB 6.3 [42]
ACT-335827 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.3 pKB 65
pKB 6.3 [65]
SB-408124 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.0 pKB 9
pKB 6.0 (KB 1x10-6 M) [9]
CVN45502 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 4.7 pKB 62
pKB 4.7 (KB 2.188x10-5 M) [62]
[3H]-almorexant Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.9 – 9.8 pKd 42-43
pKd 8.9 – 9.8 (Kd 1.25x10-9 – 1.58x10-10 M) [42-43]
[3H]Cp-1 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.2 – 9.4 pKd 42
pKd 9.2 – 9.4 (Kd 6.3x10-10 – 4x10-10 M) [42]
[3H]-TCS 1102 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.0 pKd 13
pKd 9.0 (Kd 1x10-9 M) [13]
[3H]EMPA Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.6 – 9.0 pKd 41,43,46
pKd 8.6 – 9.0 (Kd 2.51x10-9 – 1x10-9 M) [41,43,46]
[3H]SB-674042 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 6.9 pKd 38,42
pKd 6.9 [38,42]
SB-649868 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.9 – 9.8 pKi 13,17
pKi 8.9 – 9.8 [13,17]
MK-1064 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.3 pKi 59
pKi 9.3 (Ki 5x10-10 M) [59]
filorexant Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 – 9.7 pKi 13,17,56,74
pKi 9.7 [56]
pKi 8.9 – 9.1 [13,17,74]
suvorexant Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.9 – 9.5 pKi 13,17,47,56,70
pKi 9.4 [70]
pKi 8.9 – 9.5 [13,17,47,56]
ACT-462206 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 9.2 pKi 56
pKi 9.2 [56]
Cp-1 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.1 pKi 42
pKi 9.1 (Ki 7x10-10 M) 36-fold selective pro-OX2 [42]
MK-1064 Small molecule or natural product Click here for species-specific activity table Clf Antagonist 9.1 pKi 46,59
pKi 9.1 [46,59]
almorexant Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 – 9.4 pKi 41-43,70
pKi 8.6 – 9.4 [41-43,70]
suvorexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 9.0 pKi 70
pKi 9.0 [70]
MK-1064 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 9.0 pKi 46,59
pKi 9.0 [46,59]
MK-3697 Small molecule or natural product Click here for species-specific activity table Clf Antagonist 9.0 pKi 46
pKi 9.0 [46]
MK-3697 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.0 – 9.0 pKi 46,60
pKi 9.0 [46]
pKi 9.0 (Ki 1.1x10-9 M) [60]
lemborexant Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.5 – 9.3 pKi 56,77
pKi 9.3 [56]
pKi 8.5 (Ki 3x10-9 M) [77]
Description: In vitro radioligand binding assay
MK-3697 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 8.8 pKi 46
pKi 8.8 [46]
EMPA Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.4 – 9.2 pKi 41-42,56
pKi 8.4 – 9.2 790–3500-fold selective pro-OX2 [41-42,56]
MK-1064 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.7 pKi 46,59
pKi 8.7 [46,59]
MK-3697 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.7 pKi 46
pKi 8.7 [46]
pKi 8.7 [46]
HTL6641 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 8.3 – 8.6 pKi 15,56
pKi 8.6 (Ki 2.5x10-9 M) [15]
pKi 8.3 [56]
LSN2424100 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.4 pKi 21
pKi 8.4 (Ki 4.5x10-9 M) [21]
compound 11 [PMID: 15261275] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.3 pKi 44
pKi 8.3 (Ki 5.01x10-9 M) [44]
Description: Radioligand displacement assay using [125I]-orexin A as radio ligand.
seltorexant Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.1 pKi 8
pKi 8.1 (Ki 7.9x10-9 M) [8]
Description: In vitro radioligand binding assay
JNJ-10397049 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.7 – 8.4 pKi 44
pKi 7.7 – 8.4 500–630-fold selective pro-OX2 [44]
seltorexant Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.0 pKi 8
pKi 8.0 (Ki 1x10-8 M) [8]
Description: In vitro radioligand binding assay
JH112 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.3 pKi 22
pKi 7.3 (Ki 5.4x10-8 M) [22]
TCS-OX2-29 Small molecule or natural product Hs Antagonist 6.9 – 7.5 pKi 23,47
pKi 6.9 – 7.5 [23,47]
SB-674042 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.5 – 6.9 pKi 38,41
pKi 6.9 (Ki 1.29x10-7 M) [38]
pKi 6.5 [41]
SB-334867 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.2 – 6.3 pKi 9,41-42,47,51
pKi 5.2 – 6.3 [9,42,47,51]
pKi 5.2 [41]
SB-408124 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist >5.0 – 5.7 pKi 9,42
pKi >5.7 (Ki <2x10-6 M) [42]
pKi >5.0 (Ki <1x10-5 M) [9]
View species-specific antagonist tables
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]orexin A (human, mouse, rat) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs - - - 35,52,61
Useful working concentration sub nM-low nM. [35,52,61]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Adenylyl cyclase stimulation
Adenylyl cyclase inhibition
Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
Comments:  Association with the Gq family of transducers leads to phospholipase stimulation (e.g. phospholipase families A2, C and D) and Ca2+ elevation, and with the Gi family to inhibition and with the Gs family to stimulation, respectively, of adenylyl cyclase. Ca2+/non-selective cation influx also appears to rely on Gq. However, the signal transduction has not been investigated in detail in native neurons.
References:  2,18,24,26,33-37,39,55,61,68
Tissue Distribution Click here for help
Pituitary: corticotroph cells.
Species:  Human
Technique:  Immunohistochemistry
References:  7
OX: brain, lung, spleen, testis.
OX: skeletal muscle, testis, spleen > brain, lung > liver, kidney.
Species:  Mouse
Technique:  PCR
References:  14
Lymph node > bone marrow, spleen > thymus > lung > liver > kidney > spinal cord.
Species:  Mouse
Technique:  RT-PCR
References:  27
CNS: highest levels found in the cerebral neocortex, basal ganglia, hippocampal formation, hypothalamus, thalamus, midbrain, reticular formation.
Species:  Rat
Technique:  Immunohistochemistry
References:  16
Pineal gland.
Species:  Rat
Technique:  RT-PCR
References:  45
CNS: highest levels found in the cerebral cortex, nucleus accumbens, subthalamic and paraventricular thalamic nuclei, anterior pretectal nucleus.
Species:  Rat
Technique:  in situ hybridisation
References:  71
Tuberomammillary (TM) neurons in the hypothalamus.
Species:  Rat
Technique:  RT-PCR
References:  20
Pancreatic islets.
Species:  Rat
Technique:  RT-PCR
References:  49
Adrenal medulla.
Species:  Rat
Technique:  RT-PCR and immunohistrochemistry
References:  40
Brainstem: lateral reticular field (LRt) and the nucleus of the solitary tract (NTS).
Species:  Rat
Technique:  in situ hybridisation
References:  67
Olfactory system: olfactory mucosa (olfactory epithelium and lamina propria) > olfactory bulb, anterior olfactory nuclei and piriform cortex, hypothalamic and amygdala nuclei.
Species:  Rat
Technique:  immunocytochemistry
References:  12
CNS: highest levels found in the brainstem, hypothalamus, thalamus > dorsal root ganglia.
Species:  Rat
Technique:  RT-PCR
References:  16
Tissue Distribution Comments
For IHC studies, it is very important to note that selectivity issues have been raised regarding antibodies for the orexin receptors which may lead to false positive/negative results and as such, mRNA expression patterns provide important confirmatory results.
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Adenylyl cyclase and phospholipase C activation and Ca2+ elevation in HEK293 cells transfected with OX2.
Species:  Human
Tissue:  HEK293 cells
Response measured:  cAMP and inositol phosphate accumulation, Ca2+ elevation
References:  53,68
Measurement of membrane conductance in HEK 293 cells transfected with the OX2 receptor and GIRK channels.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Biphasic response: Initial phase of GIRK activation (both PTX-sensitive and insensitive) followed by long-lasting GIRK inhibition (PTX-insensitive only).
References:  24
Measurement of Ca2+ and cAMP levels in BIM hybridoma cells transfected with the OX2 receptor.
Species:  Rat
Tissue:  BIM cells
Response measured:  PTX-sensitive inhibition of cAMP accumulation and PTX-insensitive increase in [Ca2+].
References:  79
Ca2+ elevation and phospholipase C activation in CHO-K1 cells transfected with the OX2 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  PLC activity, (PLC-mediated) release of Ca2+ from intracellular stores followed by Ca2+ influx.. Possibly also receptor-operated Ca2+ influx
References:  2,25,34-35,61,64
Measurement of membrane conductance in a mixed population of tuberomammillary (TM) neurons endogenously expressing the OX2 receptor.
Species:  Rat
Tissue:  TM neurons.
Response measured:  Supression of GIRK current.
References:  24
Orexin-induced programmed cell death in CHO-S cells transfected with the OX2 receptor.
Species:  Human
Tissue:  CHO-S cells
Response measured:  Cell death
References:  72
Activation of phospholipase C and D, diacylglycerol lipase and arachidonic acid release, and regulation of adenylyl cyclase in CHO-K1 cells transfected with the OX2 receptor.
Species:  Human
Tissue:  CHO-K1 cells
Response measured:  PLC, PLD and diacylglycerol lipase activity, arachidonic acid release, adenylyl cyclase activity.
References:  34-35
Activation of ERK and p38 MAPK pathways in HEK293 cells transfected with the OX2 receptor.
Species:  Human
Tissue:  HEK293 cells
Response measured:  Stimulation of ERK and p38 phosphorylation (Western blotting)
References:  68
Physiological Functions Click here for help
Stimulation of food intake.
Species:  Rat
Tissue:  In vivo.
References:  61
Excitation of neurons known to contribute to wakefulness.
Species:  Rat
Tissue:  Tuberomammillary (TM) nuclei from histaminergic neurons..
References:  5,20
Excitation of GABAergic neurons.
Species:  Rat
Tissue:  Septohippocampal GABAergic neurons.
References:  75
Neuronal excitation of GABAergic neurones via the Na-Ca exchanger.
Species:  Mouse
Tissue:  Arcuate nucleus (ARC) neurons.
References:  11
Excitation of neurons known to be involved in the control of motivated behaviors.
Species:  Rat
Tissue:  Paraventricular nuclei of the thalamus (PVT).
References:  31
Increase in wake duration and decrease in REM and non-REM sleep.
Species:  Rat
Tissue:  In vivo.
References:  1
Inhibition of β-adrenoceptor-induced melatonin secretion and N-acetlytransferase (NAT) activity.
Species:  Rat
Tissue:  Dissociated pinealocytes.
References:  45
Excitation of neurons known to contribute to wakefulness.
Species:  Rat
Tissue:  Basal forebrain (BF) cholinergic neurons.
References:  19
Ethanol induced self-administration, place preference and behavioral reinstatement blocked by selective OX2 receptor antagonist, JNJ-10397049
Species:  Rat
Tissue:  Systemic (subcutaneous administration)
References:  63
Physiological Consequences of Altering Gene Expression Click here for help
OX2 receptor knockout mice exhibit disrupted wakefulness, abnormal attacks of non-REM sleep and elimination of orexin-evoked excitation of histaminergic neurons in the hypothalamus.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  73
Physiological Consequences of Altering Gene Expression Comments
Hcrtr2 gene disruption does not appear to result in physiological problems.
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hcrtr2tm1Ywa Hcrtr2tm1Ywa/Hcrtr2tm1Ywa
involves: 129S6/SvEvTac * C57BL/6J
MGI:2680765  MP:0001501 abnormal sleep pattern PMID: 12797957 
Hcrtr2tm1Ywa Hcrtr2tm1Ywa/Hcrtr2tm1Ywa
involves: 129S6/SvEvTac * C57BL/6J
MGI:2680765  MP:0005279 narcolepsy PMID: 12797957 
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Mouse
Description:  C-terminal splice variant of the mouse OX2 receptor, OX
Amino acids:  443
References:  14
Type:  Splice variant
Species:  Mouse
Description:  C-terminal splice variant of the OX2 receptor, OX. This variant is not found in skeletal muscle or the kidney and is upregulated in response to food deprivation.
Amino acids:  460
References:  14
Type:  Single nucleotide polymorphism
Species:  Human
Description:  This single nucleotide polymorphism is associated with a 5 fold higher risk of developing cluster headaches (CHs).
Nucleotide change:  1246G>A
References:  54

References

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78. Yukitake H, Fujimoto T, Ishikawa T, Suzuki A, Shimizu Y, Rikimaru K, Ito M, Suzuki M, Kimura H. (2019) TAK-925, an orexin 2 receptor-selective agonist, shows robust wake-promoting effects in mice. Pharmacol Biochem Behav, 187: 172794. [PMID:31654653]

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