RORA activates gene expression (Homo sapiens)

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510, 1623, 4, 9, 1914, 18171, 7, 12106, 8cytosolnucleoplasmAA PPARGC1A NPAS2 gene ferriheme b Peroxisome Proliferator Receptor Element (PPRE) p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneRORA:EP300:NPAS2geneRORANCOA6 p-S-ARNTL NRIP1 EP300 NCOR1 NR1D1NCOR1 EP300 CARM1 MED1 NR1D1 gene RORA:Coactivator:NR1D1 geneNR1D1 gene SMARCD3 NRIP1 RORA CPT1A gene EPA ARNTL geneLINA HELZ2 NPAS2 geneHDAC3 EP300 NR1D1 geneferriheme b NCOA2 RORA:Coactivator:ARNTL geneNPAS2 gene CPT1ANR1D1:heme:Corepressors:ARNTL geneNR1D1:heme:Corepressors:NPAS2 geneRORA TBL1XR1 p-S-NPAS2 CHD9 Palm ARNTLRORA PPARA:RXRACoactivator complexCPT1A geneNPAS2NR1D1 RORA EP300SIRT1ARNTL gene SREBF1(1-1147)PPARGC1AHDAC3 HDAC3 SREBF1 gene TBL1X NR1D1 NR1D1 gene RORA:EP300:CPT1AgeneNR1D1 RORA:EP300:SREBF1geneTGS1 CREBBP p-S-CLOCK EP300 NR1D1:heme:Corepressors:NR1D1 geneRXRA ARNTL gene PPARA ALA RORA ferriheme b EP300 NCOA1 NCOR1 SREBF1 genePPARGC1A 11, 131511, 132011, 13


Description

As inferred from mouse, RORA binds ROR elements (ROREs) in DNA and recruits the coactivators PPARGC1A (PGC-1alpha) and p300 (EP300, a histone acetylase) to activate transcription. View original pathway at:Reactome.

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Bibliography

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  1. Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G.; ''Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors.''; PubMed Europe PMC Scholia
  2. Kawabe Y, Honda M, Wada Y, Yazaki Y, Suzuki T, Ohba Y, Nabata H, Endo A, Matsumoto A, Itakura H.; ''Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells.''; PubMed Europe PMC Scholia
  3. Wang X, Sato R, Brown MS, Hua X, Goldstein JL.; ''SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.''; PubMed Europe PMC Scholia
  4. Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, Desvergne B.; ''DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.''; PubMed Europe PMC Scholia
  5. Britton CH, Schultz RA, Zhang B, Esser V, Foster DW, McGarry JD.; ''Human liver mitochondrial carnitine palmitoyltransferase I: characterization of its cDNA and chromosomal localization and partial analysis of the gene.''; PubMed Europe PMC Scholia
  6. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS.; ''Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells.''; PubMed Europe PMC Scholia
  7. Johnson EF, Hsu MH, Savas U, Griffin KJ.; ''Regulation of P450 4A expression by peroxisome proliferator activated receptors.''; PubMed Europe PMC Scholia
  8. Rakhshandehroo M, Hooiveld G, Müller M, Kersten S.; ''Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.''; PubMed Europe PMC Scholia
  9. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, Hua X, Goldstein JL, Brown MS.; ''SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114909view16:42, 25 January 2021ReactomeTeamReactome version 75
113354view11:42, 2 November 2020ReactomeTeamReactome version 74
112563view15:53, 9 October 2020ReactomeTeamReactome version 73
101476view11:34, 1 November 2018ReactomeTeamreactome version 66
101014view21:13, 31 October 2018ReactomeTeamreactome version 65
100550view19:47, 31 October 2018ReactomeTeamreactome version 64
100098view16:32, 31 October 2018ReactomeTeamreactome version 63
99648view15:04, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99250view12:44, 31 October 2018ReactomeTeamreactome version 62
93649view11:29, 9 August 2017ReactomeTeamreactome version 61
86765view09:25, 11 July 2016ReactomeTeamreactome version 56
83362view10:58, 18 November 2015ReactomeTeamVersion54
81526view13:04, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AA MetaboliteCHEBI:15843 (ChEBI)
ALA MetaboliteCHEBI:27432 (ChEBI)
ARNTL gene ProteinENSG00000133794 (Ensembl)
ARNTL geneGeneProductENSG00000133794 (Ensembl)
ARNTLProteinO00327 (Uniprot-TrEMBL)
CARM1 ProteinQ86X55 (Uniprot-TrEMBL)
CHD9 ProteinQ3L8U1 (Uniprot-TrEMBL)
CPT1A gene ProteinENSG00000110090 (Ensembl)
CPT1A geneGeneProductENSG00000110090 (Ensembl)
CPT1AProteinP50416 (Uniprot-TrEMBL)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
EPA MetaboliteCHEBI:28364 (ChEBI)
HDAC3 ProteinO15379 (Uniprot-TrEMBL)
HELZ2 ProteinQ9BYK8 (Uniprot-TrEMBL)
LINA MetaboliteCHEBI:17351 (ChEBI)
MED1 ProteinQ15648 (Uniprot-TrEMBL) MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
NCOA1 ProteinQ15788 (Uniprot-TrEMBL)
NCOA2 ProteinQ15596 (Uniprot-TrEMBL)
NCOA6 ProteinQ14686 (Uniprot-TrEMBL)
NCOR1 ProteinO75376 (Uniprot-TrEMBL)
NPAS2 gene ProteinENSG00000170485 (Ensembl)
NPAS2 geneGeneProductENSG00000170485 (Ensembl)
NPAS2ProteinQ99743 (Uniprot-TrEMBL)
NR1D1 ProteinP20393 (Uniprot-TrEMBL)
NR1D1 gene ProteinENSG00000126368 (Ensembl)
NR1D1 geneGeneProductENSG00000126368 (Ensembl)
NR1D1:heme:Corepressors:ARNTL geneComplexR-HSA-5663269 (Reactome)
NR1D1:heme:Corepressors:NPAS2 geneComplexR-HSA-5663274 (Reactome)
NR1D1:heme:Corepressors:NR1D1 geneComplexR-HSA-5663262 (Reactome)
NR1D1ProteinP20393 (Uniprot-TrEMBL)
NRIP1 ProteinP48552 (Uniprot-TrEMBL)
PPARA ProteinQ07869 (Uniprot-TrEMBL)
PPARA:RXRA Coactivator complexComplexR-HSA-400154 (Reactome)
PPARGC1A ProteinQ9UBK2 (Uniprot-TrEMBL)
PPARGC1AProteinQ9UBK2 (Uniprot-TrEMBL)
Palm MetaboliteCHEBI:15756 (ChEBI)
Peroxisome Proliferator Receptor Element (PPRE) R-NUL-422139 (Reactome) Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
RORA ProteinP35398 (Uniprot-TrEMBL)
RORA:Coactivator:ARNTL geneComplexR-HSA-5663268 (Reactome)
RORA:Coactivator:NR1D1 geneComplexR-HSA-5663260 (Reactome)
RORA:EP300:CPT1A geneComplexR-HSA-5663244 (Reactome)
RORA:EP300:NPAS2 geneComplexR-HSA-5663257 (Reactome)
RORA:EP300:SREBF1 geneComplexR-HSA-5663295 (Reactome)
RORAProteinP35398 (Uniprot-TrEMBL)
RXRA ProteinP19793 (Uniprot-TrEMBL)
SIRT1ProteinQ96EB6 (Uniprot-TrEMBL)
SMARCD3 ProteinQ6STE5 (Uniprot-TrEMBL)
SREBF1 gene ProteinENSG00000072310 (Ensembl)
SREBF1 geneGeneProductENSG00000072310 (Ensembl)
SREBF1(1-1147)ProteinP36956 (Uniprot-TrEMBL)
TBL1X ProteinO60907 (Uniprot-TrEMBL)
TBL1XR1 ProteinQ9BZK7 (Uniprot-TrEMBL)
TGS1 ProteinQ96RS0 (Uniprot-TrEMBL)
ferriheme b MetaboliteCHEBI:36144 (ChEBI)
p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneComplexR-HSA-5663173 (Reactome)
p-S-ARNTL ProteinO00327 (Uniprot-TrEMBL)
p-S-CLOCK ProteinO15516 (Uniprot-TrEMBL)
p-S-NPAS2 ProteinQ99743 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ARNTL geneR-HSA-1368087 (Reactome)
ARNTL geneR-HSA-400342 (Reactome)
ARNTLArrowR-HSA-400342 (Reactome)
CPT1A geneR-HSA-1801587 (Reactome)
CPT1A geneR-HSA-5663264 (Reactome)
CPT1AArrowR-HSA-1801587 (Reactome)
EP300R-HSA-1368087 (Reactome)
EP300R-HSA-5663246 (Reactome)
EP300R-HSA-5663264 (Reactome)
EP300R-HSA-5663273 (Reactome)
EP300R-HSA-5663293 (Reactome)
NPAS2 geneR-HSA-1368065 (Reactome)
NPAS2 geneR-HSA-5663246 (Reactome)
NPAS2ArrowR-HSA-1368065 (Reactome)
NR1D1 geneR-HSA-549475 (Reactome)
NR1D1 geneR-HSA-5663273 (Reactome)
NR1D1:heme:Corepressors:ARNTL geneTBarR-HSA-400342 (Reactome)
NR1D1:heme:Corepressors:NPAS2 geneTBarR-HSA-1368065 (Reactome)
NR1D1:heme:Corepressors:NR1D1 geneTBarR-HSA-549475 (Reactome)
NR1D1ArrowR-HSA-549475 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1368065 (Reactome)
PPARA:RXRA Coactivator complexArrowR-HSA-1801587 (Reactome)
PPARGC1AR-HSA-1368087 (Reactome)
PPARGC1AR-HSA-5663273 (Reactome)
R-HSA-1368065 (Reactome) The NPAS2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein. Transcription of NPAS2 is enhanced by the RORA:Coactivator complex and repressed by the REV-ERBA:Corepressor complex.
R-HSA-1368081 (Reactome) The SREBF1 (SREBP1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1368087 (Reactome) As inferred from mouse, RORA binds RRE DNA elements and recruits the coactivators PGC-1alpha (PPARGC1A), p300 (EP300, a histone acetylase), and NRIP1. Activation of BMAL1 (ARNTL) expression by ROR-alpha (RORA) is inferred from mouse. In mouse, Rora together with coactivators Ep300 and Ppargc1a bind the promoter of Bmal1 and activate transcription.
R-HSA-1801587 (Reactome) The CPT1A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-400342 (Reactome) The BMAL1 (ARNTL) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. The ROR-alpha transcription factor binds the RORE element of the BMAL1 (ARNTL) promoter and activates transcription of the BMAL1 gene. The REV-ERBA transcription factor binds the same RORE element and represses transcription of the BMAL1 gene.
R-HSA-549475 (Reactome) The NR1D1 (REV-ERBA) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. In mouse the Rev-erba gene shows circadian expression due to transactivation by the BMAL1:CLOCK (ARNTL:CLOCK) heterodimer. REV-ERBA binds the promoter of its own gene and represses its own expression (Adelmont et al. 1996).
R-HSA-5663246 (Reactome) As inferred from mouse, RORA binds RRE DNA elements and recruits the coactivators PGC-1alpha (PPARGC1A) and p300 (EP300, a histone acetylase). As inferred from mouse, ROR-alpha binds the promoter of the NPAS2 gene and enhances transcription.
R-HSA-5663264 (Reactome) As inferred from mouse, RORA binds RRE DNA elements and recruits the coactivators PGC-1alpha (PPARGC1A) and p300 (EP300, a histone acetylase). As inferred from mouse, ROR-alpha binds the promoter of the CPT1A gene and, together with coactivators EP300 and PGC-1alpha, enhances transcription.
R-HSA-5663273 (Reactome) As inferred from mouse, RORA binds RRE DNA elements and recruits the coactivators PGC-1alpha (PPARGC1A) and p300 (EP300, a histone acetylase). RORA binds the NR1D1 (REV-ERBA) promoter and activates transcription.
R-HSA-5663293 (Reactome) As inferred from mouse, RORA binds the promoter of the SREBF1 gene and recruits coactivators to enhance transcription.
RORA:Coactivator:ARNTL geneArrowR-HSA-1368087 (Reactome)
RORA:Coactivator:ARNTL geneArrowR-HSA-400342 (Reactome)
RORA:Coactivator:NR1D1 geneArrowR-HSA-549475 (Reactome)
RORA:Coactivator:NR1D1 geneArrowR-HSA-5663273 (Reactome)
RORA:EP300:CPT1A geneArrowR-HSA-1801587 (Reactome)
RORA:EP300:CPT1A geneArrowR-HSA-5663264 (Reactome)
RORA:EP300:NPAS2 geneArrowR-HSA-1368065 (Reactome)
RORA:EP300:NPAS2 geneArrowR-HSA-5663246 (Reactome)
RORA:EP300:SREBF1 geneArrowR-HSA-1368081 (Reactome)
RORA:EP300:SREBF1 geneArrowR-HSA-5663293 (Reactome)
RORAR-HSA-1368087 (Reactome)
RORAR-HSA-5663246 (Reactome)
RORAR-HSA-5663264 (Reactome)
RORAR-HSA-5663273 (Reactome)
RORAR-HSA-5663293 (Reactome)
SIRT1ArrowR-HSA-400342 (Reactome)
SREBF1 geneR-HSA-1368081 (Reactome)
SREBF1 geneR-HSA-5663293 (Reactome)
SREBF1(1-1147)ArrowR-HSA-1368081 (Reactome)
p-BMAL1:p-CLOCK,NPAS2:NR1D1 geneArrowR-HSA-549475 (Reactome)
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