NR1D1 (REV-ERBA) represses gene expression (Homo sapiens)

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Community: Reactome Comment: Reactome version 75 Revision 114863 of this pathway has been approved by the Reactome curation team (tagged by Reactome Team).

Fix interactions Comment: 1 out of 7 lines are not properly connected. Please help improving this pathway by connecting the ends of interactions to nodes.

Ontology Terms

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Bibliography

1. Yin L, Wu N, Lazar MA.; ''Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism.''; PubMed Europe PMC Scholia
2. Phelan CA, Gampe RT, Lambert MH, Parks DJ, Montana V, Bynum J, Broderick TM, Hu X, Williams SP, Nolte RT, Lazar MA.; ''Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction.''; PubMed Europe PMC Scholia
3. Raghuram S, Stayrook KR, Huang P, Rogers PM, Nosie AK, McClure DB, Burris LL, Khorasanizadeh S, Burris TP, Rastinejad F.; ''Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta.''; PubMed Europe PMC Scholia
4. Yin L, Wu N, Curtin JC, Qatanani M, Szwergold NR, Reid RA, Waitt GM, Parks DJ, Pearce KH, Wisely GB, Lazar MA.; ''Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ARNTL gene	Protein	ENSG00000133794 (Ensembl)
ARNTL gene	GeneProduct	ENSG00000133794 (Ensembl)
CLOCK gene	Protein	ENSG00000134852 (Ensembl)
CLOCK gene	GeneProduct	ENSG00000134852 (Ensembl)
ELOVL3 gene	Protein	ENSG00000119915 (Ensembl)
ELOVL3 gene	GeneProduct	ENSG00000119915 (Ensembl)
HDAC3	Protein	O15379 (Uniprot-TrEMBL)
HDAC3	Protein	O15379 (Uniprot-TrEMBL)
NCOR1	Protein	O75376 (Uniprot-TrEMBL)
NCOR1	Protein	O75376 (Uniprot-TrEMBL)
NPAS2 gene	Protein	ENSG00000170485 (Ensembl)
NPAS2 gene	GeneProduct	ENSG00000170485 (Ensembl)
NR1D1	Protein	P20393 (Uniprot-TrEMBL)
NR1D1 gene	Protein	ENSG00000126368 (Ensembl)
NR1D1 gene	GeneProduct	ENSG00000126368 (Ensembl)
NR1D1:heme:Corepressors:ARNTL gene	Complex	R-HSA-5663269 (Reactome)
NR1D1:heme:Corepressors:CLOCK gene	Complex	R-HSA-5663248 (Reactome)
NR1D1:heme:Corepressors:ELOVL3 gene	Complex	R-HSA-5663261 (Reactome)
NR1D1:heme:Corepressors:NPAS2 gene	Complex	R-HSA-5663274 (Reactome)
NR1D1:heme:Corepressors:NR1D1 gene	Complex	R-HSA-5663262 (Reactome)
NR1D1:heme:Corepressors:PPARGC1A gene	Complex	R-HSA-5663272 (Reactome)
NR1D1	Protein	P20393 (Uniprot-TrEMBL)
PPARGC1A gene	Protein	ENSG00000109189 (Ensembl)
PPARGC1A gene	GeneProduct	ENSG00000109189 (Ensembl)
ferriheme b	Metabolite	CHEBI:36144 (ChEBI)
ferriheme b	Metabolite	CHEBI:36144 (ChEBI)

Annotated Interactions

Source	Target	Type	Database reference	Comment
ARNTL gene			R-HSA-1368069 (Reactome)
CLOCK gene			R-HSA-5663271 (Reactome)
ELOVL3 gene			R-HSA-5663252 (Reactome)
HDAC3			R-HSA-1368069 (Reactome)
HDAC3			R-HSA-5663245 (Reactome)
HDAC3			R-HSA-5663252 (Reactome)
HDAC3			R-HSA-5663258 (Reactome)
HDAC3			R-HSA-5663265 (Reactome)
HDAC3			R-HSA-5663271 (Reactome)
NCOR1			R-HSA-1368069 (Reactome)
NCOR1			R-HSA-5663245 (Reactome)
NCOR1			R-HSA-5663252 (Reactome)
NCOR1			R-HSA-5663258 (Reactome)
NCOR1			R-HSA-5663265 (Reactome)
NCOR1			R-HSA-5663271 (Reactome)
NPAS2 gene			R-HSA-5663245 (Reactome)
NR1D1 gene			R-HSA-5663265 (Reactome)
	NR1D1:heme:Corepressors:ARNTL gene	Arrow	R-HSA-1368069 (Reactome)
	NR1D1:heme:Corepressors:CLOCK gene	Arrow	R-HSA-5663271 (Reactome)
	NR1D1:heme:Corepressors:ELOVL3 gene	Arrow	R-HSA-5663252 (Reactome)
	NR1D1:heme:Corepressors:NPAS2 gene	Arrow	R-HSA-5663245 (Reactome)
	NR1D1:heme:Corepressors:NR1D1 gene	Arrow	R-HSA-5663265 (Reactome)
	NR1D1:heme:Corepressors:PPARGC1A gene	Arrow	R-HSA-5663258 (Reactome)
NR1D1			R-HSA-1368069 (Reactome)
NR1D1			R-HSA-5663245 (Reactome)
NR1D1			R-HSA-5663252 (Reactome)
NR1D1			R-HSA-5663258 (Reactome)
NR1D1			R-HSA-5663265 (Reactome)
NR1D1			R-HSA-5663271 (Reactome)
PPARGC1A gene			R-HSA-5663258 (Reactome)
			R-HSA-1368069 (Reactome)	NR1D1 (REV-ERBA) binds heme. The NR1D1:heme complex is then able to recruit the corepressors NCoR and HDAC3. Corepressors do not bind NR1D1 in the absence of heme. NR1D1:heme binds a RRE element in the promoter of the ARNTL (BMAL1) gene, recruits corepressors, and represses transcription.
			R-HSA-5663245 (Reactome)	NR1D1 (REV-ERBA) binds the promoter of the NPAS2 gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
			R-HSA-5663252 (Reactome)	As inferred from mouse homologs, REV-ERBA (NR1D1) binds the promoter of the ELOVL3 gene and represses transcription, possibly by recruiting corepressors.
			R-HSA-5663258 (Reactome)	NR1D1 (REV-ERBA) binds heme and the promoter of the PGC-1alpha (PPARGC1A) gene. The REV-ERBA:heme complex recruits the corepressors NCoR and HDAC3 and represses transcription.
			R-HSA-5663265 (Reactome)	NR1D1 (REV-ERBA) binds its own promoter and represses its own expression.
			R-HSA-5663271 (Reactome)	NR1D1 (REV-ERBA) binds the promoter of the CLOCK gene and recruits corepressors to repress transcription. Recruitment of repressors appears to depend on the binding of heme by NR1D1.
ferriheme b			R-HSA-1368069 (Reactome)
ferriheme b			R-HSA-5663245 (Reactome)
ferriheme b			R-HSA-5663252 (Reactome)
ferriheme b			R-HSA-5663258 (Reactome)
ferriheme b			R-HSA-5663265 (Reactome)
ferriheme b			R-HSA-5663271 (Reactome)