Orexin receptor pathway (Homo sapiens)

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Sacroplasmic reticulum56Ca2+ effluxNucleusRegulation of receptor localizationPKC-MEKdependentPLC activationEndosomePKC dependent2-arachidonylglycerolDAGHCRTR257GH148, 49PIP2GNAS37Triglyceride productionInositol phosphateaccumulationOrexin API3K mediatedPRKD1S91610, 51HCRTR1Orexin BOrexin AOrexin BIncrease in calcium concentrationPRKD3S748S74451MAPK1Y18732, 51, 57, 61T185MAPK3Y20432, 46, 51, 57T202PRKCD51, 54T505ARBB157Orexin receptor internalizationand recyclingDYNLT155MAPK1Y1875, 34T185MAPK35, 34T202Y204MAPK8T1833, 34, 53MAPK14Y1823, 34T180SLC2A434AVP1CRH1GNAQ37GNAI137cAMPproductionDAGL dependentCalcium influxMAGLdependentArachidonic acid releasePKC dependentIncrease incalcium currentCCK6Increase in calcium concentrationARRB256PMEDMAPK156T185Y187MAPK3Y20456T202HCRTR1Increase in calcium concentrationReceptorProtein up-regulationProtein ActivationmRNA up-regulationPhosphorylation site and residueLigandInduced activation and increases protein expressionInhibitionTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation Protein-protein interactionLEGENDPhosphorylationNucleusCytoplasmPlasma membraneCYPMNUPDNAProteinProtein down-regulationmRNA down-regulationDNA bindingHCRTR2PLD154PMCYDifferentiation ofadipocytesActivation ofHPA axisAdrenal functionand energy homeostasisPituitary hormonereleaseParacrine signalingPLC activationPKC deltamediatedAdenylyl cyclaseGNASmediatedcAMPproductionDesensitizationof receptorPLCD129PMCYIP3Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ PRKCA8PMCYMAPK1T18529, 45Y187MAPK329, 45Y204T202Secretion of hormones from intestinal neuroendocrine cellsPPARG34, 59LIPE40, 59AdipogenesisPDK143S241AKT1S47311, 43FOXO143S256GCG43Glucose metabolismINS43ApoptosisMAPK1/3p38 mediatedSTAR12, 46STAR12Adreno-corticosteroidogenesisPRKCE29HCRTR118BLGAP18Regulation ofosteoblast proliferationGRIA145CREB1S13345Regulation synapticplasticity to controladdictive behaviorCYP11A146CYP11A246MAPK746Y220T218HCRTR1Y35833T83PTPN1133HCRTR133PTPN1133HSD3B246CYP11B161CYP11B261HCRTR261CYP21A261Regulation ofsteroidogenicenzymesCortisol releaseCortisolCortisolCortisolCortisolCortisolCortisol releaseCortisolCortisolCortisolCortisolCa2+ influxMEK1/2-MAPK1/3dependentiPLA2-cPLA2 alphamediatedOleicacid releaseRegulation of lipid signaling systemPIK3R159Y458AKT158, 59S473T308PDK159S241TBC1D459T642SLC2A459CYPMGlucoseuptakeIP3productionIncorporationof glucoseto NEFATriglyceride productionADIPOQ59Regulation inmetabolicdisordersCREB145S133AntidepressionHIF1A30VHL30NeuroprotectioncAMPproductionL-type channelcurrentCa2+ influxCAMKKBdependentPRKAA1T17229Regulation offeedingbehaviorNeuroprotectionto oxidativestressGHRL21LEPInhibition ofosteoblastogenesisandaugmentation ofbone formation45AKT158S473FOXO1MTOR58S25658S2481HepatocyteproliferationHCRTR158CASP32Anti-apoptoticfunctionCASP935Anti-apoptoticfunctionGNAQ53Regulation ofKOR activityMTORmediatedRPS6S244S235S236S24044RPS6KB144T389EIF4BS42244MAP2K1S21844S222MAP2K2S222S21644RPS6KA3S38044LDHA4PDK14PDHB4SLC2A1Glucose uptake4PDP14Regulation ofglucose metabolismSTAT35S727POMCRepression of satiety5PRKCA41MAPK141MAPK341SLC1A241Glutamic acid uptakeRegulation of neuron survivalfollowing hypoxicinjuryHCRTR257ARRB257HCRTR257PMCYHCRTR1ARBB15757HCRTR155, 57IL1BIL61616TNF16FOSL116AVP19Development ofhypertensionHIF1A60SLC2A160HIF1A60CYNUGlucose uptakeCASP314, 39, 60CALCA9PPOX9COX29GastroprotectionGRIN138GRIN2AGRIN2B38GRIA13838GRIA2Modulation ofexcitatory transmission incerebral cortex38FOSDevelopment ofmorphine placepreference20PLCmediatedMAPK14T180Y18223TFAMCOX7A123UCP12323PRDM1623COX8BPDIO223PPARG23CEBP23BMPR1A2323BMP723Mitochondrial biogenesisand adipogenesisNFE2L29HMOX19AngiogenesisFOS1AMHStimulation of testosterone secretion17KITLG17Inhibitory effect on spermatogonial DNA synthesisCYCS14CASP714, 60Induces apoptosisin cancerouscellsTNFAnti-inflammatoryactionPLC mediatedNFATTH47S40Catecholaminesynthesis andreleaseCYPMEndosomeEpinephrinereleaseNFKBactivityIL1B24IL624CXCL824MMP324MMP1324Anti-inflammatoryeffectVCAM1ICAM12424SELE24TNF24CAMKK224S495PRKAA124T172TNFIL1B24IL92525IL425IL1025NOX452CXCL252DRD2ARRB228Regulation ofmesolimbicdopaminergicsystem28MAPK14T180Y18210RUNX2SP71010ALPPBLGAP1010Osteoblast differentiationNeuroprotectionCOX215HSPA415BCL226BAX26CYCS26SGK122RUNX1GJA32222RARA22GLIS1HOMER122LDLR22DOK722NPAS422NOCT2222CLDN422SERP122Sleep deprivationLUZP1NR4A12222OPN3PDP122SFPQ2222PER2YARS222TRIM92222KLF4CDKN1A22HSPA52222CCN2MANF22NR4A32222DUSP422TRA2A22OSBPL3TENT5A22ZFP282222ZMYM322HAGHL22DBPEGR322EGR12222FOSL2EGR22222HBEGF22MAFF22HMGA222JUNB22NOG22PAPPAGADD45B22ARC22CXXC522TNC2222SKIL22DCLK1ID322FOS22LRRC8C2222IRF522ID122SPP122RUNX1T1HES122MYC2222BHLH40SRF2222FOSB22GLIS222HMGA1ID42222KLF10RUNX222KCNK32222EpinephrineNorepinepinephrineproductioncAMPproductionPLC-PKCmediatedIP3productionAC-PKCmediatedCortisolsecretionLeads to through known mechanismHIF1A7VEGFA7FLT47NOS37VHL30PDP17FMR1NBJARID27PDE11A7NSMAF7LAMA277OPA17CD24IL47CLEC4C77TOX7DDX52BTF377Gq-PLC mediated13Gi/0mediated36Decrease inCalciumFeedingbehaviorGq-PLCmediated36Acetyl-cholinerelease42Regulationof arousal/wakefulnessCatecholaminesecretionPKAmediated36GlucocorticoidsecretionAutocrine-paracrineregulation ofadrenal secretionAcetyl-cholineefflux27AKT1S47350HSD3B150Enhances cellsurvival, proliferationand glucocorticoid secretionIncrease inCalciumRegulation of testicular functionLH and FSHreleaseGonadotropinreleaseDecrease inprogesteroneRegulatory role in ovary31TestosteronereleaseCholecyctokininreleaseFeedback regulationStimulation of metabolite releaseIncrease indopamineHCRTR2HCRTR23737HCRTR237


Description

The collective depiction of the

signal transduction mechanisms and the signaling cascades associated with orexin will help scientists improve the current knowledge of orexinergic system. This pathway illustration provides the downstream effectors and the varied physiological outcomes associated with

differential stimulation of orexin receptors.

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Bibliography

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  1. Mazzocchi G, Malendowicz LK, Gottardo L, Aragona F, Nussdorfer GG; ''Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade.''; J Clin Endocrinol Metab, 2001 PubMed Europe PMC Scholia
  2. Zheng D, Zhao Y, Shen Y, Chang X, Ju S, Guo L; ''Orexin A-mediated stimulation of 3β-HSD expression and testosterone production through MAPK signaling pathways in primary rat Leydig cells.''; J Endocrinol Invest, 2014 PubMed Europe PMC Scholia
  3. Chen L, Zhao Y, Zheng D, Ju S, Shen Y, Guo L; ''Orexin A Affects INS-1 Rat Insulinoma Cell Proliferation via Orexin Receptor 1 and the AKT Signaling Pathway.''; Int J Endocrinol, 2013 PubMed Europe PMC Scholia
  4. Guo Y, Feng P; ''OX2R activation induces PKC-mediated ERK and CREB phosphorylation.''; Exp Cell Res, 2012 PubMed Europe PMC Scholia
  5. Zhang H, Liang B, Li T, Zhou Y, Shang D, Du Z; ''Orexin A Suppresses Oxidized LDL Induced Endothelial Cell Inflammation via MAPK p38 and NF-κB Signaling Pathway.''; IUBMB Life, 2018 PubMed Europe PMC Scholia
  6. Evans NA, Groarke DA, Warrack J, Greenwood CJ, Dodgson K, Milligan G, Wilson S; ''Visualizing differences in ligand-induced beta-arrestin-GFP interactions and trafficking between three recently characterized G protein-coupled receptors.''; J Neurochem, 2001 PubMed Europe PMC Scholia
  7. Kim MK, Park HJ, Kim SR, Choi YK, Bae SK, Bae MK; ''Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells.''; Korean J Physiol Pharmacol, 2015 PubMed Europe PMC Scholia
  8. Chang X, Zhao Y, Guo L; ''Effect of Orexin-A on Cortisol Secretion in H295R Cells via p70S6K/4EBP1 Signaling Pathway.''; Int J Endocrinol, 2015 PubMed Europe PMC Scholia
  9. Karteris E, Randeva HS, Grammatopoulos DK, Jaffe RB, Hillhouse EW; ''Expression and coupling characteristics of the CRH and orexin type 2 receptors in human fetal adrenals.''; J Clin Endocrinol Metab, 2001 PubMed Europe PMC Scholia
  10. Wu WN, Wu PF, Zhou J, Guan XL, Zhang Z, Yang YJ, Long LH, Xie N, Chen JG, Wang F; ''Orexin-A activates hypothalamic AMP-activated protein kinase signaling through a Ca²�-dependent mechanism involving voltage-gated L-type calcium channel.''; Mol Pharmacol, 2013 PubMed Europe PMC Scholia
  11. Tang J, Chen J, Ramanjaneya M, Punn A, Conner AC, Randeva HS; ''The signalling profile of recombinant human orexin-2 receptor.''; Cell Signal, 2008 PubMed Europe PMC Scholia
  12. Hefshejanni JA, Khazali H; ''Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats.''; Exp Clin Endocrinol Diabetes, 2019 PubMed Europe PMC Scholia
  13. Kukkonen JP; ''G-protein-dependency of orexin/hypocretin receptor signalling in recombinant Chinese hamster ovary cells.''; Biochem Biophys Res Commun, 2016 PubMed Europe PMC Scholia
  14. Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya I, Yamashita H; ''Centrally administered orexin/hypocretin activates HPA axis in rats.''; Neuroreport, 2000 PubMed Europe PMC Scholia
  15. Tunisi L, D'Angelo L, Fernández-Rilo AC, Forte N, Piscitelli F, Imperatore R, de Girolamo P, Di Marzo V, Cristino L; ''Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice.''; Front Synaptic Neurosci, 2021 PubMed Europe PMC Scholia
  16. Barreiro ML, Pineda R, Navarro VM, Lopez M, Suominen JS, Pinilla L, Señaris R, Toppari J, Aguilar E, Diéguez C, Tena-Sempere M; ''Orexin 1 receptor messenger ribonucleic acid expression and stimulation of testosterone secretion by orexin-A in rat testis.''; Endocrinology, 2004 PubMed Europe PMC Scholia
  17. Pruszynska-Oszmalek E, Kolodziejski PA, Kaczmarek P, Sassek M, Szczepankiewicz D, Mikula R, Nowak KW; ''Orexin A but not orexin B regulates lipid metabolism and leptin secretion in isolated porcine adipocytes.''; Domest Anim Endocrinol, 2018 PubMed Europe PMC Scholia
  18. Voisin T, El Firar A, Rouyer-Fessard C, Gratio V, Laburthe M; ''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.''; FASEB J, 2008 PubMed Europe PMC Scholia
  19. Valiante S, Liguori G, Tafuri S, Pavone LM, Campese R, Monaco R, Iachetta G, Assisi L, Mirabella N, Forte M, Costagliola A, Vittoria A; ''Expression and potential role of the peptide orexin-A in prostate cancer.''; Biochem Biophys Res Commun, 2015 PubMed Europe PMC Scholia
  20. Cataldi NI, Lux Lantos VA, Libertun C; ''Orexin A and B in vitro modify orexins receptors expression and gonadotropins secretion of anterior pituitary cells of proestrous rats.''; Regul Pept, 2014 PubMed Europe PMC Scholia
  21. Turunen PM, Jäntti MH, Kukkonen JP; ''OX1 orexin/hypocretin receptor signaling through arachidonic acid and endocannabinoid release.''; Mol Pharmacol, 2012 PubMed Europe PMC Scholia
  22. Shin SK, Song SE, Oh JU, Hwang M, Cho HW, Bae JH, Im SS, Kim JI, Song DK; ''Orexin A-induced inhibition of leptin expression and secretion in adipocytes reducing plasma leptin levels and hypothalamic leptin resistance.''; Pflugers Arch, 2019 PubMed Europe PMC Scholia
  23. Huber MJ, Fan Y, Jiang E, Zhu F, Larson RA, Yan J, Li N, Chen QH, Shan Z; ''Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension.''; Am J Physiol Heart Circ Physiol, 2017 PubMed Europe PMC Scholia
  24. Xiong X, White RE, Xu L, Yang L, Sun X, Zou B, Pascual C, Sakurai T, Giffard RG, Xie XS; ''Mitigation of murine focal cerebral ischemiaby the hypocretin/orexin system is associated with reduced inflammation.''; Stroke, 2013 PubMed Europe PMC Scholia
  25. Xu R, Roh SG, Gong C, Hernandez M, Ueta Y, Chen C; ''Orexin-B augments voltage-gated L-type Ca(2+) current via protein kinase C-mediated signalling pathway in ovine somatotropes.''; Neuroendocrinology, 2003 PubMed Europe PMC Scholia
  26. Kukkonen JP, Akerman KE; ''Orexin receptors couple to Ca2+ channels different from store-operated Ca2+ channels.''; Neuroreport, 2001 PubMed Europe PMC Scholia
  27. Wang C, Xu C, Liu M, Pan Y, Bai B, Chen J; ''C-terminus of OX2R significantly affects downstream signaling pathways.''; Mol Med Rep, 2017 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
135195view00:48, 8 August 2024EweitzRefine legend
135194view00:47, 8 August 2024EweitzEconomize layout
126204view21:39, 14 April 2023Khansperstried moving data nodes to front
126201view14:15, 14 April 2023Ash iyerannotations
126189view12:23, 14 April 2023Ash iyerCorrecting miss-annotated datanodes
126170view08:25, 12 April 2023Ash iyerRemoved title of the pathway
126169view08:20, 12 April 2023Ash iyerAnnotation of missing nodes
126136view11:59, 11 April 2023Ash iyerUpdated the nodes annotation for some.
126135view11:58, 11 April 2023Ash iyerUpdated some of teh datanodes databases incorrectly annotataed.
126134view11:53, 11 April 2023Ash iyerSome nodes with error in databse selection have been corrected. But many other similar corrections have to be done.
126125view08:51, 11 April 2023Ash iyerModified title
126115view18:56, 7 April 2023Khanspersconverted interactions to graphical lines where appropriate, added xrefs
124542view04:17, 8 November 2022EweitzModified description
124541view04:17, 8 November 2022EweitzModified description
120665view00:11, 23 December 2021EweitzStandardize font, weight, case
119886view05:59, 10 September 2021EgonwUndo revision 119878: it reverts earlier changes. Please use the latest version from WikiPathways when making updates. Otherwise other people keep seeing their work undone by overwrites.
119878view06:43, 6 September 2021KeshavOrexin Signalling Pathway
119637view06:24, 27 July 2021EgonwCorrected the data source
119542view14:49, 14 July 2021KeshavUpdated
118951view10:24, 5 June 2021EweitzOntology Term : 'neurotransmitter metabolic pathway' added !
118950view10:23, 5 June 2021EweitzOntology Term : 'signaling pathway pertinent to the brain and nervous system' added !
118947view06:08, 5 June 2021EgonwUpdated data sources for NCBI Protein
116377view19:45, 4 May 2021KeshavOntology Term : 'signaling pathway' added !
116376view19:43, 4 May 2021KeshavModified description
116375view19:38, 4 May 2021KeshavNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2-arachidonyl glycerolMetabolite
ADIPOQProtein9370 (Entrez Gene) [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces upregulation of ADIPOQ protein in a PPARG dependent manner in 3T3-L1 adipocytes and primary adipocytes from wistar rats.
AKT1ProteinNP_005154.2 (NCBI Protein) [Pubmed:25319929] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of AKT1 at Ser473 in NCI-H295R cells.
ALPPRna250 (Entrez Gene)
  • [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ALPP mRNA in a RUNX2 dependent manner in MC3T3-E1 cells.
  • [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces activation of ALPP in a RUNX2 dependent manner in MC3T3-E1 cells.
AMHRna268 (Entrez Gene) [Pubmed:16141395] have shown that Ox-A stimulates HCRTR1 and induces downregulation of AMH mRNA in rat testis.
ARBB1ProteinNP_004032.2 (NCBI Protein) [Pubmed:21378163] have shown that Ox-A stimulates HCRTR1 and induces molecular association between HCRTR1 and ARRB1 in HEK293T cells.
ARCRna23237 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ARC mRNA in GT1-7 cells.
ARRB2ProteinNP_001244257.1 (NCBI Protein) [Pubmed:33613258] have shown that Ox-A stimulates molecular association of DRD2 and ARRB2 in a PLC/DAGL/2AG/CB1 loop mediated dopamine release which desensitizes the dopamine receptor in mouse ventral tegmental area and nucleus accumbens.
ARRB2ProteinNP_004032.2 (NCBI Protein) [Pubmed:15683363] have shown that OxA stimulates HCRTR1 and induces association of HCRTR1 and ARRB2 in HEK 293 cells.
AVPProtein551 (Entrez Gene) [Pubmed:28667055] have shown that Ox-A stimulates HCRTR1 and induces upregulation of AVP mRNA in rat PVN neurons.
Acetyl-

choline

efflux		Metabolite
Acetyl-

choline

release		Metabolite
Arachidonic acid releaseMetabolite
BAXProtein581 (Entrez Gene) [Pubmed:24135219] have shown that Ox-A stimulates HCRTR1/2 and induces downregulation of BAX protein in 6-OHDA induced SH-SY5Y cells.
BCL2Protein596 (Entrez Gene) [Pubmed:24135219] have shown that Ox-A stimulates HCRTR1/2 and induces upregulation of BCL2 protein in 6-OHDA induced SH-SY5Y cells.
BHLH40Rna8553 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BHLH40 mRNA in GT1-7 cells.
BLGAPRna632 (Entrez Gene) [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BLGAP mRNA in a RUNX2 dependent manner in MC3T3-E1 cells.
BMP7Rna655 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BMP7 mRNA in C3H10T1/2 cells.
BMPR1ARna7019 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BMPR1A mRNA in C3H10T1/2 cells.
BTF3Rna689 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BTF3 mRNA in HEK293 cells.
CALCARna796 (Entrez Gene) [Pubmed:18378017] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CALCA mRNA in rat gastric mucosa.
CAMKK2ProteinNP_006540.3 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces phosphorylation of CAMKK2 at Ser495 in intracerebral heamorrhagic mouse brain.
CASP3ProteinNP_004337.2 (Entrez Gene)
  • [Pubmed:15310763] have shown that Ox-A/B stimulates HCRTR1 and induces activation of CASP3 in HT29-D4 cells.
  • [Pubmed:22588980] have shown that Ox-A stimulates HCRTR1 and induces activation of CASP3 in rat C6 glioma cells.
CASP3ProteinNP_004337.2 (NCBI Protein) [Pubmed:25586545] have shown that Ox-A stimulates HCRTR1 and induces inhibition of CASP3 in PI3K-AKT dependent manner in BGC-829 cells.
CASP7ProteinNP_203124.1 (Entrez Gene) [Pubmed:15310763] have shown that Ox-A/B stimulates HCRTR1 and induces activation of CASP7 in HT29-D4 cells.
CASP9ProteinNP_001220.2 (NCBI Protein) [Pubmed:25515760] have shown that Ox-A stimulates HCRTR1 and induces inhibition of CASP9 in a MAPK1/3 dependent manner in SGC-7901 cells.
CCKProtein2688 (Entrez Gene) [Pubmed:12943684] have shown that Ox-A stimulates HCRTR1 and HCRTR2 and induces the upregulation of CCK in STC1 cells
CCN2Rna1490 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CCN2 mRNA in GT1-7 cells.
CD24Rna100133941 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CD24 mRNA in HEK293 cells.
CDKN1ARna1026 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CDKN1A mRNA in GT1-7 cells.
CEBPRna1050 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CEBPA mRNA in C3H10T1/2 cells.
CLDN4Rna1364 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CLDN4 mRNA downstream of SGK1 in GT1-7 cells.
CLEC4CRna170482 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CLEC4C mRNA in HEK293 cells.
COX2Protein6775079 (Entrez Gene) [Pubmed:27814668] have shown that Ox-A stimulates HCRTR1 and induces downregulation of COX2 protein in 6-OHDA treated SH-SY5Y cells.
COX7A1Rna1346 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of COX7A1 mRNA in C3H10T1/2 cells.
COX8BPRna404544 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of COX8BP mRNA in C3H10T1/2 cells.
CREB1ProteinNP_604391.1 (NCBI Protein) [Pubmed:22652455] have shown that Ox-B stimulates HCRTR2 and induces phosphorylation of CREB at Ser133 in a PKC dependent manner in CHO-OXR2 cells.
CRHRna1392 (Entrez Gene) [Pubmed:11328451] have shown that Ox-A stimulates HCRTR2 and induces upregulation of CRH mRNA in rat PVN neurons.
CXCL2Protein2920 (Entrez Gene) [Pubmed:31106596] have shown that Ox-A stimulates HCRTR1 and induces downregulation of CXCL2 protein in HBx transfected L-02 and MIHA hepatocytes.
CXCL8Protein3576 (Entrez Gene) [Pubmed:30142537] have shown that Ox-A stimulates HCRTR1 and induces downregulation of CXCL8 protein in TNF alpha treated fibroblast-like synoviocytes.
CXXC5Rna51523 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CXXC5 mRNA in GT1-7 cells.
CYCSProtein54205 (Entrez Gene) [Pubmed:24135219] have shown that Ox-A stimulates HCRTR1/2 and induces downregulation of CYCS protein in 6-OHDA induced SH-SY5Y cells.
CYP11A1Rna1583 (Entrez Gene) [Pubmed:19460850] have shown that Ox-B stimulates HCRTR1 and induces upregulation of CYP11A1 mRNA in H295R adernocortical cells.
CYP11A2Rna1589 (Entrez Gene) [Pubmed:19460850] have shown that Ox-A or Ox-B stimulates HCRTR1 and induces upregulation of CYP21A2 mRNA in H295R adernocortical cells.
CYP11B1Rna1584 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces downregulation of CYP11B1 mRNA in H295R adrenal cells.
CYP11B2Rna1585 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces downregulation of CYP11B2 mRNA in H295R adrenal cells.
CYP21A2Rna1589 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces upregulation of CYP21A2 mRNA in H295R adrenal cells.
Calcium

influx

Pathway
Cholecyctokinin releaseMetabolite
Cortisol secretionMetabolite
Cortisol releaseMetabolite
DAGMetabolite
DAGL dependentPathway
DBPRna1628 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces downregulation of DBP mRNA in GT1-7 cells.
DCLK1Rna9201 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of DCLK1 mRNA in GT1-7 cells.
DDX52Rna11056 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of DDX52 mRNA in HEK293 cells.
DIO2Rna1734 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of DIO2 mRNA in C3H10T1/2 cells.
DOK7Rna285489 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of DOK7 mRNA downstream of SGK1 in GT1-7 cells.
DRD2ProteinNP_000786.1 (NCBI Protein) [Pubmed:33613258] have shown that Ox-A stimulates molecular association of DRD2 and ARRB2 in a PLC/DAGL/2AG/CB1 loop mediated dopamine release which desensitizes the dopamine receptor in mouse ventral tegmental area and nucleus accumbens.
DUSP4Rna1846 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of DUSP4 mRNA in GT1-7 cells.
DYNLT1ProteinNP_006510.1 (NCBI Protein) [Pubmed:22028875] have shown that Ox-A stimulates HCRTR1 and induces molecular association between HCRTR1 and DYNLT1 in HEK293 cells.
Decrease in CalciumMetabolite
Decrease in progesteroneMetabolite
EGR1Rna1958 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of EGR1 mRNA in GT1-7 cells.
EGR2Rna1959 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of EGR2 mRNA in GT1-7 cells.
EGR3Rna1960 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of EGR3 mRNA in GT1-7 cells.
EIF4BProteinNP_001287750.1 (NCBI Protein) [Pubmed:25278019] have shown that OX-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of EIF4B on Ser422 under the lysosome v-ATPase-RAG-GTPase pathway activating MTORC1 in HEK293T and N41 neural cells.
Epinephrine

Norepinepinephrine

production		Metabolite
Epinephrine releaseMetabolite
FLT4Rna2324 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FLT4 mRNA in a HIF1A dependent manner in rat hypothalamus and HEK293 cells.
FMR1NBRna158521 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FMR1NB mRNA in HEK293 cells.
FOSRna2353 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FOS mRNA in GT1-7 cells.
FOSBRna2354 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FOSB mRNA in GT1-7 cells.
FOSL1Protein8061 (Entrez Gene) [Pubmed:28872777] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FOSL1 in rat PVN neurons and PC12 cells.
FOSL2Rna2355 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of FOSL2 mRNA in GT1-7 cells.
FOXO1ProteinNP_002006.2 (NCBI Protein) [Pubmed:24807827] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of FOXO1 at Ser256 in a PI3K-AKT dependent manner in rat hepatocytes.
GADD45BRna4616 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GADD45B mRNA in GT1-7 cells.
GCGProtein2641 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces downregulation of GCG protein in InR-G9 cells.
GH1Protein2688 (Entrez Gene)
  • [Pubmed:12673048] have shown that OxB stimulates HCRTR2 and induces upregulation of GH1 in ovine somatotropes.
  • [Pubmed:14610299] have shown that OxB stimulates HCRTR2 and induces upregulation of GH1 in ovine somatotropes
GHRLProtein51738 (NCBI Protein) [Pubmed:24794976] have shown that Ox-A stimulates HCRTR1 and induces downregulation of GHRL protein in mouse osteoblast and adipocyte.
GJA3Rna2700 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GJA3 mRNA downstream of SGK1 in GT1-7 cells.
GLIS1Rna148979 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GLIS1 mRNA downstream of SGK1 in GT1-7 cells.
GLIS2Rna84662 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GLIS2 mRNA in GT1-7 cells.
GNAI1GeneProductNP_002060.4 (Entrez Gene) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAI1 in human adult adrenals.
GNAQGeneProductNP_002063.2 (Entrez Gene) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAQ in human adult adrenals.
GNAQProteinNP_002063.2 (NCBI Protein) [Pubmed:25857454] have shown that Ox-A stimulates HCRTR1 and induces activation of GNAQ in CHO cells.
GNASGeneProductNP_536350.2 (Entrez Gene) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAS in human adult adrenals.
GRIA1Rna2890 (Entrez Gene) [Pubmed:18573570] have shown that OxA/B stimulate HCRTR2 and induce downregulation of GRIA1 mRNA in rat primary neurons.
GRIA1Protein2980 (NCBI Protein) [Pubmed: 19028455] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GRIA1 protein in rat prefrontal cortex-striatum coculture
GRIA2Rna2891 (Entrez Gene) [Pubmed:18573570] have shown that OxA/B stimulate HCRTR2 and induce downregulation of GRIA2 mRNA in rat primary neurons.
GRIN1Rna2902 (Entrez Gene) [Pubmed:18573570] have shown that OxA/B stimulate HCRTR2 and induce downregulation of GRIN1 mRNA in rat primary neurons.
GRIN2ARna2903 (Entrez Gene) [Pubmed:18573570] have shown that OxA/B stimulate HCRTR2 and induce downregulation of GRIN2A mRNA in rat primary neurons.
GRIN2BRna2904 (Entrez Gene) [Pubmed:18573570] have shown that OxA/B stimulate HCRTR2 and induce downregulation of GRIN2B mRNA in rat primary neurons.
Glucocorticoid secretionMetabolite
Glucose uptakeMetabolite
Glucose uptakeMetabolite
Glutamic acid uptakeMetabolite
HAGHLRna84264 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces downregulation of HAGHL mRNA in GT1-7 cells.
HBEGFRna1839 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HBEGF mRNA in GT1-7 cells.
HCRTR1Rna3061 (Entrez Gene) [Pubmed:19020772] have shown that Ox-A and Ox-B stimulates HCRTR1 and induces upregulation of HCRTR1 mRNA in rat calvarial osteoblast-like cells
HCRTR1GeneProductNP_001516.2 (Entrez Gene)
  • [Pubmed:21378163] have shown that Ox-A stimulates HCRTR1 and induces translocation of HCRTR1 from plasma membrane to cytoplasm in HEK293T cells.
  • [Pubmed:22028875] have shown that Ox-A stimulates HCRTR1 and induces transport of HCRTR1 from plasma membrane to cytoplasm in HEK293 cells.
  • [Pubmed:28886081] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HCRTR1 mRNA in HepG2 cells.
HCRTR1ProteinNP_001516.2 (NCBI Protein) [Pubmed:21378163] have shown that Ox-A stimulates HCRTR1 and induces association of HCRTR1 and ARRB1 in HEK293FT cell lines.
HCRTR2GeneProduct3061 (Entrez Gene)
HCRTR2Rna3062 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces downregulation of HCRTR2 mRNA within 6 hours of treatment on H295R adrenal cells.
HCRTR2ProteinNP_001517.2 (NCBI Protein) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAQ in human adult adrenals.
HES1Rna3280 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HES1 mRNA in GT1-7 cells.
HIF1AProtein3091 (Entrez Gene) [Pubmed:28886081] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HIF1A mRNA in HepG2 cells.
HIF1AProteinNP_001521.1 (NCBI Protein) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces activation of HIF1A in HEK293 cells and rat hypothalamus.
HMGA1Rna3159 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HMGA1 mRNA in GT1-7 cells.
HMGA2Rna8091 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HMGA2 mRNA in GT1-7 cells.
HMOX1Rna4780 (Entrez Gene)
  • [Pubmed:26170736] have shown that Ox-A stimulates HCRTR1/2 and induces activation of NFE2L2 in HUVECs.
  • [Pubmed:26170736] have shown that Ox-A stimulates HCRTR1/2 and induces upregulation of HMOX1 mRNA downstream of NFE2L2 in HUVECs.
HOMER1Rna9456 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HOMER1 mRNA downstream of SGK1 in GT1-7 cells.
HSD3B1Protein3283 (Entrez Gene) [Pubmed:25319929] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HSD3B1 protein in a AKT dependent manner in NCI-H295R cells.
HSD3B2Rna3284 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces upregulation of HSD3B2 mRNA in a calcium-PKC-MEK1/2-MAPK1/3 mediated pathway in H295R adrenal cells.
HSPA4Protein3308 (Entrez Gene) [Pubmed:27814668] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HSPA4 protein in 6-OHDA treated SH-SY5Y cells.
HSPA5Rna3309 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HSPA5 mRNA in GT1-7 cells.
ICAM1Rna3383 (Entrez Gene) [Pubmed:30207631] have shown that Ox-A stimulates HCRTR1 and induces downregulation of ICAM1 protein in LPL induced HUVECs.
ID1Rna3397 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ID1 mRNA in GT1-7 cells.
ID3Rna3399 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ID3 mRNA in GT1-7 cells.
ID4Rna3400 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ID4 mRNA in GT1-7 cells.
IL10Protein3586 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces upregulation of IL10 protein in a CAMKK2/PRKAA mediated manner in intacerebral hemorrhagic mouse brain.
IL1BProtein3553 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces downregulation of IL1B protein in a CAMKK2/PRKAA mediated manner in intacerebral hemorrhagic mouse brain.
IL4Rna3565 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of IL4 mRNA in HEK293 cells.
IL6Protein3569 (Entrez Gene) [Pubmed:30142537] have shown that Ox-A stimulates HCRTR1 and induces downregulation of IL6 protein in TNF alpha treated fibroblast-like synoviocytes.
IL9Protein3578 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces downregulation of IL9 protein in a CAMKK2/PRKAA mediated manner in intacerebral hemorrhagic mouse brain.
INSProtein3630 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces upregulation of INS protein secretion in InR-G9 cells.
IP3Metabolite
IP3 productionMetabolite
IRF5Rna3663 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of IRF5 mRNA in GT1-7 cells.
Increase in CalciumMetabolite
Increase in

calcium

current		Pathway
Increase in dopamineMetabolite
Increase in

calcium

concentration		Pathway
Inositol

phosphate

accumulation		Metabolite
JARID2Rna3720 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of JARID2 mRNA in HEK293 cells.
JUNBRna3726 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of JUNB mRNA in GT1-7 cells.
KCNK3Rna3777 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of KCNK3 mRNA downstream of SGK1 in GT1-7 cells.
KITLGRna4254 (Entrez Gene) [Pubmed:16141395] have shown that Ox-A stimulates HCRTR1 and induces downregulation of AMH mRNA in rat testis.
KLF10Rna7071 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of KLF10 mRNA in GT1-7 cells.
KLF4Rna9314 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of KLF4 mRNA in GT1-7 cells.
LAMA2Rna3908 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LAMA2 mRNA in HEK293 cells.
LDHAGeneProduct3939 (Entrez Gene) [Pubmed:26549689] have shown that OX-A stimulates HCRTR1 and induces downregulation of LDHA mRNA in Hep3B cells.
LDLRRna3949 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LDLR mRNA downstream of SGK1 in GT1-7 cells.
LEPProtein3952 (NCBI Protein) [Pubmed:24794976] have shown that Ox-A stimulates HCRTR1 and induces downregulation of LEP protein in mouse serum.
LH and FSH releaseMetabolite
LIPEProtein3991 (Entrez Gene)
  • [Pubmed:17065396] have shown that Ox-A and Ox-B stimulates HCRTR1 and HCRTR2 and induces downregulation of LIPE mRNA in human omental adipose tissue.
  • [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces downregulation of LIPE mRNA in 3T3-L1 adipocytes and primary adipocytes from Wistar rats.
LRRC8CRna84230 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LRRC8C mRNA in GT1-7 cells.
LUZP1Rna7798 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LUZP1 mRNA in GT1-7 cells.
MAFFRna23764 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of MAFF mRNA in GT1-7 cells.
MAGL dependentPathway
MANFRna7873 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of MANF mRNA in GT1-7 cells.
MAP2K1ProteinNP_002746.1 (NCBI Protein) [Pubmed:25278019] have shown that Ox-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of MAP2K1 at Ser218 and Ser222 under influence of calcium influx in N41 neuronal cells.
MAP2K2ProteinNP_109587.1 (NCBI Protein) [Pubmed:25278019] have shown that Ox-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of MAP2K2 at Ser216 and Ser222 under influence of calcium influx in N41 neuronal cells.
MAPK14ProteinNP_001306.1 (NCBI Protein) [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 an dinduces phosphorylation of MAPK14 at Thr180 and Tyr182 in a PKD dependent manner in MC3T3-E1 cells.
MAPK1GeneProduct5594 (Entrez Gene) [Pubmed: 27837432] have shown that Orexin-A stimulates OX1R and induces an upregulation of MAPK1 protein in astrocytes of Neonatal Sprague-Dwaley rats.
MAPK1ProteinNP_002736.3 (NCBI Protein)
  • [Pubmed:16141359] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK1 at Thr185 and Tyr187 in a Calcium dependent manner in CHO cells.
  • [Pubmed:19028455] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK1 at Thr185 and Tyr187 in rat prefrontal cortex-striatum coculture
MAPK3GeneProduct5595 (Entrez Gene) [Pubmed: 27837432] have shown that Orexin-A stimulates OX1R and induces an upregulation of MAPK3 protein in astrocytes of Neonatal Sprague-Dwaley rats.
MAPK3ProteinNP_002737.2 (NCBI Protein)
  • [Pubmed:16141359] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK3 at Thr202 and Tyr204 in a Calcium dependent manner in CHO cells.
  • [Pubmed:19028455] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK3 at Thr202 and Tyr204 in rat prefrontal cortex-striatum cocultures
MAPK7ProteinNP_620602.2 (NCBI Protein) [Pubmed:19460850] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK7 at Thr218 and Tyr220 in H295R(Human) adrenocortical cells.
MAPK8ProteinNP_620637.1 (NCBI Protein)
  • [Pubmed:23907013] have shown that Ox-a stimulates HCRTR1 and induces phosphorylation of MAPK8 in 3T3-L1 adipocytes.
  • [Pubmed: 16282319] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK8 at Thr183 in CHO-OX1R cells
  • [Pubmed:25857454] have shown that Ox-a stimualtes HCRTR1 and induces phosphorylation of MAPK8 at Thr183 in a GNAQ dependent manner in CHO cells.
MMP13Rna4322 (Entrez Gene) [Pubmed:30142537] have shown that Ox-A stimulates HCRTR1 and induces downregulation of MMP13 mRNA in TNF alpha treated fibroblast-like synoviocytes.
MMP3Rna4314 (Entrez Gene) [Pubmed:30142537] have shown that Ox-A stimulates HCRTR1 and induces downregulation of MMP3 mRNA in TNF alpha treated fibroblast-like synoviocytes.
MTORProteinNP_004949.1 (NCBI Protein) [Pubmed:24807827] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MTOR at Ser2481 in a PI3K-AKT dependent manner in rat hepatocytes.
MYCRna4609 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of MYC mRNA in GT1-7 cells.
NFE2L2Protein4780 (Entrez Gene)
  • [Pubmed:26170736] have shown that Ox-A stimulates HCRTR1/2 and induces upregulation of NFE2L2 protein in HUVECs.
  • [Pubmed:26170736] have shown that Ox-A stimulates HCRTR1/2 and induces activation of NFE2L2 in HUVECs.
NOCTRna25819 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NOCT mRNA downstream of SGK1 in GT1-7 cells.
NOGRna9241 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NOG mRNA in GT1-7 cells.
NOS3Rna4846 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NOS3 mRNA in a HIF1A dependent manner in rat hypothalamus and HEK293 cells.
NOX4Protein50507 (Entrez Gene) [Pubmed:31106596] have shown that Ox-A stimulates HCRTR1 and induces downregulation of NOX4 protein in HBx transfected L-02 and MIHA hepatocytes.
NPAS4Rna266743 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NPAS4 mRNA downstream of SGK1 in GT1-7 cells.
NR4A1Rna3164 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NR4A1 mRNA in GT1-7 cells.
NR4A3Rna8013 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NR4A3 mRNA in GT1-7 cells.
NSMAFRna8439 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of NSMAF mRNA in HEK293 cells.
OPA1Rna4976 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of OPA1 mRNA in HEK293 cells.
OPN3Rna23596 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of OPN3 mRNA in GT1-7 cells.
OSBPL3Rna26031 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of OSBPL3 mRNA in GT1-7 cells.
Oleic acid releaseMetabolite
Orexin AGeneProduct100 (Entrez Gene)
Orexin BGeneProduct100 (Entrez Gene)
Orexin receptor

internalization

and recycling		Pathway
PAPPARna5069 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PAPPA mRNA in GT1-7 cells.
PDE11ARna50940 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PDE11A mRNA in HEK293 cells.
PDHBGeneProduct5162 (Entrez Gene) [Pubmed:26549689] have shown that OX-A stimulates HCRTR1 and induces upregulation of PDHB mRNA in Hep3B cells.
PDK1GeneProduct5163 (Entrez Gene) [Pubmed:26549689] have shown that OX-A stimulates HCRTR1 and induces downregulation of PDK1 mRNA in Hep3B cells.
PDK1ProteinNP_001265478.1 (NCBI Protein) [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces phosphorylation of PDK1 at Ser241 in a PI3K dependent manner in 3T3-L1 adipocytes and primary adipocytes from wistar rats.
PDP1Rna54704 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PDP1 mRNA in a HIF1A dependent manner in HEK293 cells.
PDP1GeneProductNP_001155251.1 (NCBI Protein) [Pubmed:26549689] have shown that Ox-A stimulates HCRTR1 and induces activation of PDP1 in Hep3B cells. [
PER2Rna8864 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PER2 mRNA in GT1-7 cells.
PI3K mediatedGeneProduct
PIK3R1ProteinNP_852664.1 (NCBI Protein) [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces phosphorylation of PIK3R1 at Tyr458 in 3T3-L1 adipocytes and primary adipocytes from wistar rats.
PIP2Metabolite
PKC dependentPathway
PLCD1Protein5333 (NCBI Protein) [Pubmed:16141359] have shown that Ox-A stimulates HCRTR1 and induces the translocation of PLCD1 from plasma membrane to cytoplasm in CHO cells.
PLD1ProteinNP_002653.1 (NCBI Protein) [Pubmed:21718304] have shown that Ox-A stimulates HCRTR1 and induces activation of PRKCD in CHO-OxR1 cells.
POMCProtein5443 (NCBI Protein) [Pubmed:27071101] have shown that Ox-A stimulates HCRTR1 and induces downregulation of POMC protein in a MAPK1/3-STAT3 dependent manner in mouse POMC cells.
PPARGRna5468 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PPARG mRNA in C3H10T1/2 cells.
PPOXRna5498 (Entrez Gene) [Pubmed:18378017] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PPOX mRNA in rat gastric mucosa.
PRDM16Rna63976 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PRDM16 mRNA in C3H10T1/2 cells.
PRKAA1ProteinNP_996790.3 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces phosphorylation of PRKAA1 at Thr172 in intracerebral heamorrhagic mouse brain.
PRKAA1ProteinNP_996790.3 (NCBI Protein) [Pubmed:24068427] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PRKAA1 at Thr172 in a Camkkbeta-Calcium dependent manner in rat hypothalamic nuclear neurons.
PRKCAGeneProduct5578 (Entrez Gene) [Pubmed: 27837432] have shown that Orexin-A stimulates OX1R and induces an upregulation of PRKCA protein in astrocytes of Neonatal Sprague-Dwaley rats.
PRKCAProtein5578 (NCBI Protein) [Pubmed:18488139] have shown that Ox-A stimulates HCRTR1 and induces the translocation of PRKCA from cytosol to plasma membrane in CHO cell lines.
PRKCDProteinNP_001341605.1 (NCBI Protein)
  • [Pubmed:20621130] have shown that OX-A stimulates HCRTR1 and induces phosphorylation of PRKCD at Thr505 in HEKOX1R cells.
  • [Pubmed:21718304] have shown that Ox-A stimulates HCRTR1 and induces activation of PRKCD in CHO-OxR1 cells.
PRKCEProtein5581 (NCBI Protein) [Pubmed:16141359] have shown that Ox-A stimulates HCRTR1 and induces the translocation of PRKCE from plasma membrane to cytosol in CHO cell lines.
PRKD1ProteinNP_001316998.1 (NCBI Protein)
  • [Pubmed:20621130] have shown that OX-A stimulates HCRTR1 and induces phosphorylation of PRKD1 at Ser916 in HEKOX1R cells.
  • [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PRKD1 in MC3T3-E1 cells.
PRKD3ProteinNP_005804.1 (NCBI Protein) [Pubmed:20621130] have shown that OX-A stimulates HCRTR1 and induces phosphorylation of PRKD3 at Ser744/748 in HEKOX1R cells.
PTPN11GeneProductNP_001317366.1 (Entrez Gene) [Pubmed:19661287] have shown that Ox-A stimulates HCRTR1 and induces activation of PTPN11 in CHO-OX1 cells.
RARARna5914 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of RARA mRNA downstream of SGK1 in GT1-7 cells.
RPS6KA3ProteinNP_004577.1 (NCBI Protein) [Pubmed:25278019] have shown that Ox-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of RPS6KA3 at Ser380 in a MEK1/2 dependent manner under influence of calcium influx in N41 neuronal cells.
RPS6KB1ProteinNP_003152.1 (NCBI Protein) [Pubmed:25278019] have shown that OX-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of RPS6KB1 on Thr389 under the lysosome v-ATPase-RAG-GTPase pathway activating MTORC1 in HEK293T and N41 neural cells.
RPS6ProteinNP_001001.2 (NCBI Protein) [Pubmed:25278019] have shown that OX-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of RPS6 on Ser235/236 and Ser240/244 under the lysosome v-ATPase-RAG-GTPase pathway activating MTORC1 in HEK293T and N41 neural cells.
RUNX1Rna861 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of RUNX1 mRNA downstream of SGK1 in GT1-7 cells.
RUNX1T1Rna862 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces downregulation of RUNX1T1 mRNA in GT1-7 cells.
RUNX2Rna860 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of RUNX2 mRNA in GT1-7 cells.
SELERna6401 (Entrez Gene) [Pubmed:30207631] have shown that Ox-A stimulates HCRTR1 and induces downregulation of SELE protein in LPL induced HUVECs.
SERP1Rna27230 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SERP1 mRNA downstream of SGK1 in GT1-7 cells.
SFPQRna6241 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SFPQ mRNA in GT1-7 cells.
SGK1Rna6446 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SGK1 mRNA in GT1-7 cells.
SKILRna6498 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SKIL mRNA in GT1-7 cells.
SLC1A2GeneProduct6506 (Entrez Gene) [Pubmed: 27837432] have shown that Orexin-A stimulates OX1R and induces an upregulation of SLC1A2 protein in astrocytes of Neonatal Sprague-Dwaley rats.
SLC2A1Protein6513 (Entrez Gene) [Pubmed:28886081] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SLC2A1 protein in a AKT/MTOR/HIF1A manner in HepG2 cells.
SLC2A4Protein6517 (Entrez Gene) [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces translocation of SLC2A4 from cytoplasm to plasma membrane in a PI3K-AKT dependent pathway in 3T3-L1 rat adipocytes and primary rat adipocytes from Wistar rats.
SP7Rna121340 (Entrez Gene) [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SP7 mRNA in a RUNX2 dependent manner in MC3T3-E1 cells.
SPP1Rna6696 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SPP1 mRNA in GT1-7 cells.
SRFRna6722 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SRF mRNA in GT1-7 cells.
STARProtein6770 (Entrez Gene) [Pubmed: 18450961]have shown that Ox-A or Ox-B stimulates HCRTR1 and induces the upregulation of STAR protein mediated through ERK1/2 dependent and p38 dependent MAPK cascades in human H295R adrenal cells.
STAT3ProteinNP_001356441.1 (NCBI Protein) [Pubmed:27071101] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of STAT3 at Ser727 downstream of MAPK1/3 in mouse POMC neurons.
TBC1D4ProteinNP_055647.2 (NCBI Protein) [Pubmed:21505958] have shown that Ox-A stimulates HCRTR1/HCRTR2 and induces phosphorylation of TBC1D4 at Thr642 in a PI3K-AKT dependent manner in 3T3-L1 adipocytes and primary adipocytes from wistar rats.
TENT5ARna55603 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TENT5A mRNA in GT1-7 cells.
TFAMRna7019 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TFAM mRNA in C3H10T1/2 cells.
THProteinNP_954986.2 (NCBI Protein) [Pubmed:23635422] have shown that Ox-A/B stimulate HCRTR1/2 and induce phosphorylation of TH at Ser40 in bovine adrenal medulla cells.
TNCRna3371 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TNC mRNA in GT1-7 cells.
TNFProtein7124 (Entrez Gene) [Pubmed:31106596] have shown that Ox-A stimulates HCRTR1 and induces downregulation of TNF protein in HBx transfected L-02 and MIHA hepatocytes.
TOXRna9760 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TOX mRNA in HEK293 cells.
TRA2ARna29896 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TRA2A mRNA in GT1-7 cells.
TRIM9Rna114088 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of TRIM9 mRNA in GT1-7 cells.
Testosterone releaseMetabolite
Triglyceride productionMetabolite
UCP1Rna7350 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of UCP1 mRNA in C3H10T1/2 cells.
VCAM1Rna7412 (Entrez Gene) [Pubmed:30207631] have shown that Ox-A stimulates HCRTR1 and induces downregulation of VCAM1 protein in LPL induced HUVECs.
VEGFARna7422 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of VEGFA mRNA in a HIF1A dependent manner in rat hypothalamus and HEK293 cells.
VHLProtein7428 (Entrez Gene) [Pubmed:21239965] have shown that Ox-A stimulates HCRTR1 and induces downregulation of VHL protein in rat hippocampal neurons.
YARS2Rna51067 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of YARS2 mRNA in GT1-7 cells.
ZFP28Rna140612 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces downregulation of ZFP28 mRNA in GT1-7 cells.
ZMYM3Rna9203 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces downregulation of ZMYM3 mRNA in GT1-7 cells.
cAMP productionMetabolite

Annotated Interactions

No annotated interactions

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