Orexin receptor pathway (Homo sapiens)

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MAPK94MAPK315, 24Y204T20217MAP2K2S222S216LysosomeRegulation ofMesenchymalStem CellDifferentiationOR /BOTHIncreased Epinephrinesecretion from adrenal medullary cellsOrexin Signaling PathwayApoptosis pathway Increased expressionIn anoxia /hypoglycemicastrocytesGenes transcriptionally regulatedby orexin A in GT1-7-OX1 (hypothalamic neurons derived HCRTR1-expressed cell line)Promotesosteogenicdifferentiation& mineralizationmTORC1Potentialregulation ofhypothalamic-pituitary-gonadal axisLysosome v-ATPasePathwayMap LegendIncreasedsurfaceexpression in striatumCatecholaminebiosynthesisin adrenalmedullary cellsIn hypothalamicneuronsNeuro-protectiveeffectCortisolsecretion inAdrenocortical cells (H295R) Orexin-A effect is Gs/Gq/Gi- dependent Orexin-B effect is Gq-dependent 1Modulation ofKappa opioidreceptor - Gaisignaling Studied for Orexin A and not Orexin B Studied for Orexin B and not Orexin A Studied for both but predominenty Orexin A dependent Studied for both but predominenty Orexin B dependent Studied for both and induced by both Studied with HCRTR1 modulation and not HCRTR2 Studied with HCRTR2 modulation and not HCRTR1 Studied for both but predominenty HCRTR1 dependent Studied for both but predominenty HCRTR2 dependent Studied for both and dependent on both Not studied for both and receptor dependency unknown Based on receptor expression HCRTR1 (predominent) Based on receptor expression HCRTR2 (predominent) Based on receptor expression (may be both) In parvocellular cells of PVN on i.c.v injection Secretion ofosteocalcin in osteoblast-like(ROB) cellsAdenylatecyclaseIn pre- anddifferentiated 3T3-L1 adipocytes1NPFFR1OPRK121PIK3R1HSD3B2mRNAmRNAModulation ofexcitatory transmission incerebral cortexFMR1NBJARID2PDE11ANSMAFLAMA2OPA1CD24IL4CLEC4CTOXDDX52BTF3HCRTR1MAPK8T183T185MAPK1422, 24T180Y182MAPK1T18515, 22, 24Y187PPARGSLC2A45GlucosemetabolismIn differentiated 3T3-L1 adipocytesAVP12CRHHCRTR2FOS8Potential activationof HPA axis throughCRF and AVP neuronstimulationLIPEPPARGLPLLIPELPLIn subcutaneousHCRTR1 and R2mRNA expressingadipose tissueexplantsGCGReduced pro-glucagonbiosynthesis inglucagon-producingInR1-G9 cellsGlucoseCREB1S13318PDPK1S241AKT1S473FOXO1S256PI3KCatalyticMAP2K1S222S218GNASGNAI19, 10GNAQ10PKASTARSTARAdreno-corticosteroidogenesisin H295R cellsBGLAPCGA26LHB26 Reduced Glycerol release in omental adipose tissue Secretion of LH & FSH gonadotropins in Primary anteriorpituatory cellsCGA26FSHB26HCRTR2Increased HCRTR1expression counteractstestosterone-induced nucleartransloaction ofAndrogen Receptorin LnCaP cellsHCRTR120, 26Regulation ofexpression ofHCRTR1/2 inPrimary anteriorpituatory cellsLHFSHMAPK7Y220T218CYP11A1CYP21A2CortisolCYP11B1CYP11B2TriglycerideProduction1HCRTR22611cAMP1, 1511ARRB11HCRTR1Y836Y358ARRB11717HCRTR1ARRB2HCRTR1ARRB1ARRB217ARRB2Cell deathin HCRTR1-transfectedCHO-K1 cellsIP36, 15, 22Ca2+44 Release from ER4, 27DAGPIP2PIP314Ca2+4L-typeCalciumchannels27CNR125THS40Voltage-gatedCa2+ and Na+channelsCCKGlycerolCCKCholecystokininsecretion inSTC-1 cellsGH14GrowthHormonesecretion insomatotropesTestosteroneTestosteronesecretion intesticular cells20, 2420Cytochrome CCytochrome CCASP7CASP3 Apoptosis in OX1R+ HT29-D4, SK-N-MC, C6 & CHO cell lines17 Sustained HCRTR1-ARRB2 interaction prolonged MAPK1/3 activation in HEK-293T HCRTR1+ cellsPLCD1PRKCEPRKCZHIF1AIncreasedglucoseutilization inhypothalamicneuronsVHLHIF1ALDHAPDK1PDHBActivationof PDH and Suppresionof lactate productionin adipocytesGCGPTPN116PRKCAT638IP1IP2GRIN1GRIN2AGRIN2BGRIA1GRIA2In corticalneuronsGRIA1PRKCDT505PRKCBT641PRKD1S916PRKD3S744S748HCRTR2ARRB1ARRB21515HCRTR2ARRB2ARRB1151515PIK3R2SLC2A4SLC2A45IncreasedGlucose/stimulatedinsulinsecretion inINS-1 cellsADIPOQAdiponectinsecretion inadipocytesIncreasedglucoseuptake inadipocytesPLD1BMP7BMPR1ABMP7BMPR1ASMAD1S463SMAD5S465PRDM16DYNLT1DYNLT3 Regulation of receptor internalizationHCRTR1Regulation ofexpression ofHCRTR1/2 inleuteal cellsProgesteroneDecreasedProgesteronesecretion byluteal cellsReceptor internalization and recyclingEpinephrinePRKAA1T17227IncreasedNeuropeptide Yproduction andregulation offeedingbehaviorCAMKK227NPY27INS3Reducedglucagonsecretion inglucagon-producingInR1-G9 cellsPro-survival /anti-apoptoticfunctions inINS-1 cells &BGC-823 gastriccancer cells3HCRTR119Regulation ofexpression ofHCRTR1 inINS-1 cellsInhibition ofosteoblastogenesisand augmentationof bone formationGHRLLEPMTORS2481HepatocyteproliferationRPS6S235S236S240S244RPS6KB1T389EIF4BS422RPS6KA1S380MTORRRAGCGTPDAGLACASP92Pro-survival /anti-apoptotic functions inSGC-7901 cellsEIF4EBP116T46T37Cortisolsecretionin H295Rcells16NFE2L211HMOX111AngiogenesisNFE2L211HMOX111CASP33Proliferation /anti-apoptoticfunctions inH295R cellsSLC2A1SLC2A1Increasedglucose uptake inHep3B & HepG2 cellsActivationof PDH andMitochondrialglucoseoxidation inHep3B/G2 cells2-AGMAPK3T202Y204MAPK1T185Y187STAT3S727POMCRepression of satietyPOMC Reduced alpha-MSH release in ARC primary neuronsNRF2 pathwayGNA119SLC2A1PDHBRUNX1GJA3RARAGLIS1HOMER1LDLRDOK7NPAS4NOCTCLDN4SERP1KCNK3LUZP1NR4A1OPN3PDP1SFPQPER2YARS2TRIM9KLF4CDKN1AHSPA5CCN2MANFNR4A3DUSP4TRA2AOSBPL3TENT5AEGR3EGR1FOSL2EGR2ARCHBEGFMAFFHMGA2JUNBNOGPAPPAGADD45BCXXC5TNCSKILDCLK1ID3FOSLRRC8CIRF5ID1SPP1HES1MYCBHLH40SRFFOSBGLIS2HMGA1ID4KLF10RUNX2ZFP28ZMYM3HAGHLDBPRUNX1T1Sleep deprivationSGK1SGK1 Genes regulated by SGK1 Regulation oflipogenesis and lipolysisLEP5LEP5, 23Regulationof leptinsecretion inadipocytesLEPVEGFAFLT4NOS3PDP1In hypothalamicneuronsIn hypothalamicneuronsPRKCAMAPK1MAPK3Glutamicacid uptakeRegulation of neuron survivalfollowing hypoxicinjurySLC1A2SLC1A2SLC1A2Glutamic acidIn anoxia /hypoglycemicastrocytesTFAMCOX7A1UCP1COX8BPDIO2PPARGCEBPAMitochondrialbiogenesisand brown fatadipogenesisCYPMCa2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+PMCYCYECCYPMCYECCYECGlucoseCYECCYECCYECCYECCYECCYPMCYPMCYPMCYPMCYPMCYPMCYPMCYECSRC family6HCRTHCRTHCRTHCRTRUNX2SP7ALPPBGLAPCALCAPPOXCOX2GastroprotectionIncorporationof glucoseto NEFA inadipocytesTriglycerideproduction2-AG Decreased expressionMetaboliteProteinProtein Protein function activation Regulation of gene expression Protein-protein interaction Protein activity inhibition Leads to through known or unknown mechanisms (Multiple colored edges are used to delineate the interconnectivity across crossing edges)Protein Protein family/specific subunits or isozymes not reported in studies Protein phosphosite & residueCYPM Protein transportNUEC Plasma membrane Cytoplasm Nucleus ExtracellularReceptorOrexin AProtein Receptor hypersensitizationNUCYMTCYGNRH121NPVF21IL6CXCL8MMP3MMP13VCAM113ICAM113SELE13TNFTNF7, 13IL1BIL9IL4IL10NOX4CXCL2Anti-inflammatoryresponse of orexinin IntracerebralhemorrhageProteinXnnn MitochondriaMT Protein cleavagePA25AAPLA2G4A252514Orexin B


Description

Depiction of a compendium of the orexin stimulated reactions involving the signal transduction mechanisms and downstream effectors associated with the varied physiological outcomes.

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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

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NameTypeDatabase referenceComment
2-AGMetaboliteC13856 (KEGG Compound)
AAMetaboliteC00219 (KEGG Compound)
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:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of AKT1 at Ser473 in InR1-G9 cell line
  • [Pubmed:26459696] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of AKT1 at Ser473 in a PI3K dependent manner in H295R adrenocorticoid 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.
ARCRna23237 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of ARC mRNA in GT1-7 cells.
ARRB1ProteinNP_004032.2 (NCBI Protein) [Pubmed:28487995] have shown that Ox-A/Ox-B stimulate HCRTR2 and induce molecular association of HCRTR2 and ARRB1 in HEK293 cells.
ARRB2ProteinNP_001244257.1 (NCBI Protein) [Pubmed:28487995] have shown that Ox-A/Ox-B stimulate HCRTR2 and induce molecular association of HCRTR2 and ARRB2 in HEK293 cells.
AVPRna551 (Entrez Gene) [Pubmed:11328451] have shown that Ox-A stimulates HCRTR2 and induces upregulation of AVP mRNA in rat PVN neurons.
BGLAPRna632 (Entrez Gene) [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BGLAP mRNA in a RUNX2 dependent manner in MC3T3-E1 cells.
BGLAPProteinNP_954642.1 (NCBI Protein) [Pubmed:19020772] have shown that Ox-B stimulates HCRTR1 and induces upregulation of BGLAP protein in rat calvarial osteoblast-like cells.
BHLH40Rna8553 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BHLH40 mRNA in GT1-7 cells.
BMP7Protein655 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of BMP7 mRNA in C3H10T1/2 cells.
BMPR1AProtein657 (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.
CAMKK2Protein10645 (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.
CASP3ProteinNP_620637.1 (NCBI Protein) [Pubmed:24382962] have shown that Ox-A stimulates HCRTR1 and induces inhibition of CASP3 in a PI3K-AKT dependent pathway in INS1 cells.
CASP7ProteinNP_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: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.
CEBPARna1050 (Entrez Gene) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces upregulation of CEBPA mRNA in C3H10T1/2 cells.
CGAProtein1081 (Entrez Gene) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAI1 in human adult adrenals.
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.
CNR1GeneProduct3062 (Entrez Gene)
COX2Protein6775079 (Entrez Gene) [Pubmed:18378017] have shown that Ox-A stimulates HCRTR1 and induces upregulation of COX2 protein in rat gastric mucosa.
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 CREB1 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.
CYP11A1Rna1583 (Entrez Gene) [Pubmed:19460850] have shown that Ox-B stimulates HCRTR1 and induces upregulation of CYP11A1 mRNA in H295R adernocortical cells.
CYP11B1Rna1584 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces upregulation of CYP11B1 mRNA in H295R adrenal cells.
CYP11B2Rna1585 (Entrez Gene) [Pubmed:19793950] have shown that Ox-A stimulates HCRTR2 and induces upregulation 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.
  • [Pubmed:19460850] have shown that Ox-A or Ox-B stimulates HCRTR1 and induces upregulation of CYP21A2 mRNA in H295R adernocortical cells.
Ca2+Metabolite
Ca2+MetaboliteC00076 (KEGG Compound)
CortisolMetaboliteC00735 (KEGG Compound)
Cytochrome CMetaboliteC00125 (KEGG Compound)
DAGMetabolite
DAGLAProtein747 (NCBI Protein) [Pubmed:33613258] have shown that Ox-A stimulates HCRTR1 and induces activation of DAGLA in TH positive neurons in mice.
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.
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.
DYNLT3Protein6990 (NCBI Protein) [Pubmed:22028875] have shown that Ox-A stimulates HCRTR1 and induces molecular association between HCRTR1 and DYNLT1 in HEK293 cells.
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.
EIF4EBP1ProteinNP_004086.1 (NCBI Protein) [Pubmed:26064108] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of EIF4EBP1 at Thr37 and Thr46 in a MTOR mediated manner in H295R cells.
EpinephrineMetaboliteC00788 (KEGG Compound)
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.
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:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of FOXO1 at Ser256 in InR1-G9 cell line.
FSHBProtein2488 (Entrez Gene) [Pubmed:24333629] have shown that Ox-A/B stimulate HCRTR1/2 and induces upregulation of FSHB in rat anterior pituitary cells.
GADD45BRna4616 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of GADD45B mRNA in GT1-7 cells.
GCGRna2641 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces downregulation of GCG protein in InR-G9 cells.
GH1Protein2688 (NCBI Protein) [Pubmed:14610299] have shown that Ox-B stimulates HCRTR2 and induces upregulation of GH1 protein 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.
GNA11Protein2767 (NCBI Protein) [Pubmed:27237973] have shown that Ox-A/B stimulates HCRTR1 and induces molecular association of HCRTR1 and GNA11 in CHO-K1 cells.
GNAI1GeneProductNP_002060.4 (NCBI Protein) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAI1 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.
  • [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAQ in human adult adrenals.
GNASGeneProductNP_536350.2 (NCBI Protein) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAS in human adult adrenals.
GNRH1Protein2796 (Entrez Gene) [Pubmed:31091547] have shown that Ox-A stimulates HCRTR1 and induces downregulation of GNRH1 mRNA in rats.
GRIA1Rna2890 (Entrez Gene) [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.
Glucose metabolismPathway
GlucoseMetaboliteC00031 (KEGG Compound)
Glutamic

acid

uptake		MetaboliteC00025 (KEGG Compound)
Glutamic acidMetaboliteC00025 (KEGG Compound)
GlycerolMetaboliteC00116 (KEGG Compound)
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.
HCRTProtein3060 (Entrez Gene) [Pubmed:11600545] have shown that Ox-A stimulates HCRTR2 and induces molecular association of HCRTR2 and GNAI1 in human adult adrenals.
HCRTR1GeneProduct3061 (Entrez Gene) [Pubmed:26220343] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HCRTR1 mRNA in LNCaP cells.
HCRTR1ProteinNP_001516.2 (NCBI Protein) [Pubmed:19661287] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of HCRTR1 at Tyr83 and Tyr358 in CHO-OX1 cells.
HCRTR2GeneProduct3062 (Entrez Gene)
HES1Rna3280 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of HES1 mRNA in GT1-7 cells.
HIF1AGeneProduct3091 (Entrez Gene)
  • [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces activation of HIF1A in HEK293 cells and rat hypothalamus.
  • [Pubmed:28886081] have shown that Ox-A stimulates HCRTR1 and induces translocation of HIF1A from cytoplasm to nucleus in HepG2 cells.
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.
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 within 12 hours of treatment on H295R adrenal 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.
IL4Protein3565 (Entrez Gene) [Pubmed:32539736] have shown that Ox-A stimulates HCRTR2 and induces upregulation of IL4 protein in a CAMKK2/PRKAA mediated manner in intacerebral hemorrhagic mouse brain.
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.
INSRna3630 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces upregulation of INS protein secretion in InR-G9 cells.
IP1Metabolite
IP2Metabolite
IP3Metabolite
IRF5Rna3663 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of IRF5 mRNA in GT1-7 cells.
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.
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.
L-type

Calcium channels

ProteinNP_001265478.1 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PDK1 at Ser241 in InR1-G9 cell line.
LAMA2Rna3908 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LAMA2 mRNA in HEK293 cells.
LDHARna3939 (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.
LEPRna3952 (Entrez Gene) [Pubmed:29413903] have shown that Ox-A stimulates HCRTR1 and induces upregulation of LEP mRNA in porcine adipocytes.
LEPRna3952 (NCBI Protein) [Pubmed:24794976] have shown that Ox-A stimulates HCRTR1 and induces downregulation of LEP protein in mouse serum.
LHBProtein3972 (Entrez Gene) [Pubmed:24333629] have shown that Ox-A/B stimulate HCRTR1/2 and induces upregulation of LHB in rat anterior pituitary cells.
LIPERna3991 (Entrez Gene)
  • [Pubmed:17065396] have shown that Ox-A/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.
LPLRna4023 (Entrez Gene) [Pubmed:17065396] have shown that Ox-A/B stimulates HCRTR1 and HCRTR2 and induces upregulation of LPL mRNA in human subcutaneous adipose tissue.
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.
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:23907013] have shown that Ox-a stimulates HCRTR1 and induces phosphorylation of MAPK14 in 3T3-L1 adipocytes.
  • [Pubmed:16282319] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK14 at Thr180 and Tyr182 in CHO-OX1 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:27071101] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK1 at Thr185 and Tyr187 in mouse POMC neurons.
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:27071101] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK3 at Thr202 and Tyr204 in mouse POMC neurons.
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.
MAPK9ProteinNP_002743.3 (NCBI Protein)
  • [Pubmed:23907013] have shown that Ox-a stimulates HCRTR1 and induces phosphorylation of MAPK9 in 3T3-L1 adipocytes.
  • [Pubmed: 16282319] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of MAPK9 at Thr183 in CHO-OX1R cells
  • [Pubmed:25857454] have shown that Ox-a stimualtes HCRTR1 and induces phosphorylation of MAPK9 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:25278019] have shown that OX-A/B stimulates HCRTR1 and/or HCRTR2 and induces activation of MTOR in HEK293T and N41 neural cells.
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.
NPFFR1Protein64106 (Entrez Gene) [Pubmed:31091547] have shown that Ox-A stimulate HCRTR1/2 and induce upregulation of NPFFR1 mRNA in rat brain.
NPVFProtein64111 (Entrez Gene) [Pubmed:31091547] have shown that Ox-A stimulate HCRTR1/2 and induce upregulation of NVPF mRNA in rat brain.
NPYProtein4852 (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.
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.
OPRK1Protein4986 (Entrez Gene)
OSBPL3Rna26031 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of OSBPL3 mRNA in GT1-7 cells.
PAMetaboliteC00416 (KEGG Compound)
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.
PDHBProtein5162 (Entrez Gene) [Pubmed:26549689] have shown that OX-A stimulates HCRTR1 and induces upregulation of PDHB mRNA in Hep3B cells.
PDK1Rna5163 (Entrez Gene) [Pubmed:26549689] have shown that OX-A stimulates HCRTR1 and induces downregulation of PDK1 mRNA in Hep3B cells.
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.
PDPK1ProteinNP_001248745.1 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PDK1 at Ser241 in InR1-G9 cell line.
PER2Rna8864 (Entrez Gene) [Pubmed:29145494] have shown that Ox-A stimulates HCRTR1 and induces upregulation of PER2 mRNA in GT1-7 cells.
PI3K CatalyticProteinNP_001265478.1 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PDK1 at Ser241 in InR1-G9 cell line.
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PIP2Metabolite
PIP3Metabolite
PKAProtein5578 (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.
PLA2G4AProtein5321 (NCBI Protein)
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.
PLD1Protein5337 (Entrez Gene) [Pubmed:21718304] have shown that Ox-A stimulates HCRTR1 and induces activation of PLD1 in a PRKCD dependent manner 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 (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:20621130] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PRKCA at Thr638 in HEK OX1R cells.
PRKCBProtein5579 (NCBI Protein) [Pubmed:20621130] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PRKCB at Thr641 in HEK OX1R cells.
PRKCDProtein5580 (NCBI Protein) [Pubmed:20621130] have shown that OX-A stimulates HCRTR1 and induces phosphorylation of PRKCD at Thr505 in HEKOX1R 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.
PRKCZProtein5590 (NCBI Protein)
PRKD1ProteinNP_001316998.1 (NCBI Protein) [Pubmed:20621130] have shown that OX-A stimulates HCRTR1 and induces phosphorylation of PRKD1 at Ser916 in HEKOX1R 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 (NCBI Protein)
  • [Pubmed:19661287] have shown that Ox-A stimulates HCRTR1 and induces activation of PTPN11 in CHO-OX1 cells.
  • [Pubmed:18198212] have shown that Ox-A stimulates HCRTR1 and induces molecular association of HCRTR1 and PTPN11 in CHO-hOX1R cells.
ProgesteroneMetaboliteC00410 (KEGG Compound)
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.
RPS6KA1ProteinNP_002944.2 (NCBI Protein) [Pubmed:25278019] have shown that Ox-A/B stimulates HCRTR1 and/or HCRTR2 and induces phosphorylation of RPS6KA1 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.
RRAGCProtein64121 (NCBI Protein) [Pubmed:25278019] have shown that OX-A/B stimulates HCRTR1 and/or HCRTR2 and induces activation of RRAGC 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.
RUNX2Protein860 (Entrez Gene) [Pubmed:29999239] have shown that Ox-A stimulates HCRTR1 and induces upregulation of RUNX2 protein in a PKD/MAPK14 dependent manner in MC3T3-E1 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.
SGK1Protein6446 (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.
SLC2A1Rna6513 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SLC2A1 mRNA in a HIF1A dependent manner in rat hypothalamus and HEK293 cells.
SLC2A4Protein6517 (Entrez Gene) [Pubmed:23907013] have shown that Ox-A stimulates HCRTR1 and induces upregulation of SLC2A4 mRNA in 3T3-L1 adipocytes.
SMAD1ProteinNP_001341740.1 (NCBI Protein) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of SMAD1 at Ser463 downstream of BMPR1A in C3H10T1/2 cells.
SMAD5ProteinNP_001001419.1 (NCBI Protein) [Pubmed:21982708] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of SMAD5 at Ser465 downstream of BMPR1A in C3H10T1/2 cells.
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 upregulation of STAR mRNA through MAPK cascades in human H295R adrenocortical cells.
  • [Pubmed:19460850] have shown that Ox-A or Ox-B stimulates HCRTR1 and induces upregulation of STAR mRNA in H295R adernocortical 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.
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.
TestosteroneMetaboliteC00535 (KEGG Compound)
TriglycerideMetaboliteC00422 (KEGG Compound)
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.
VHLGeneProduct7428 (Entrez Gene) [Pubmed:18006690] have shown that Ox-A stimulates HCRTR1 and induces downregulation of VHL protein in HEK293 cells and rat hypothalamus.
Voltage-gated

Ca2+ and Na+ channels

ProteinNP_001265478.1 (NCBI Protein) [Pubmed:18162514] have shown that Ox-A stimulates HCRTR1 and induces phosphorylation of PDK1 at Ser241 in InR1-G9 cell line.
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.
cAMPMetaboliteC00575 (KEGG Compound)

Annotated Interactions

No annotated interactions

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