Nr1d2
entrez
353187
canonical
uniprot
Q60674
canonical
ensembl
ENSMUSG00000021775
resolver
ensp
ENSMUSP00000088031
resolver
ensp
ENSMUSP00000307571
resolver
ensp
ENSMUSP00000307572
resolver
ensp
ENSMUSP00000307576
resolver
ensp
ENSMUSP00000307578
resolver
ensp
ENSMUSP00000307583
resolver
ensp
ENSMUSP00000307585
resolver
ensp
ENSMUSP00000307586
resolver
enst
ENSMUST00000090543
resolver
genesymbol
Nr1d2
resolver
uniprot
Q4VAB7
resolver
uniprot
Q60646
resolver
uniprot
Q8C598
resolver
uniprot
Q8C6J1
resolver
uniprot_entry
NR1D2_MOUSE
resolver
uniprot_entry
Q4VAB7_MOUSE
resolver
uniprot_entry
Q8C598_MOUSE
resolver
uniprot_entry
Q8C6J1_MOUSE
resolver
uniprot_sec
Q60646
resolver
activity_regulation
ACTIVITY REGULATION: The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MELNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNCDANGNPKNADISSIDGVLKSDRTDCPVKTGKTSAPGMTKSHSGMTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMNTQFSGHLQNDTLAEQHDQSALPAQEQLRPKSQLEQENIKNTPSDFAKEEVIGMVTRAHKDTFLYNQEHRENSSESMPPQRGERIPRNMEQYNLNQDHRGSGIHNHFPCSERQQHLSGQYKGRNIMHYPNGHAVCIANGHCMNFSSAYTQRVCDRIPVGGCSQTENRNSYLCNTGGRMHLVCPMSKSPYVDPQKSGHEIWEEFSMSFTPAVKEVVEFAKRIPGFRDLSQHDQVNLLKAGTFEVLMVRFASLFDAKERTVTFLSGKKYSVDDLHSMGAGDLLSSMFEFSEKLNALQLSDEEMSLFTAVVLVSADRSGIENVNSVEALQETLIRALRTLIMKNHPNEASIFTKLLLKLPDLRSLNNMHSEELLAFKVHP
uniprot
proteins
function
FUNCTION: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle. Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (PubMed:29355503). Key regulator of skeletal muscle mitochondrial function; negatively regulates the skeletal muscle expression of core clock genes and genes involved in mitochondrial biogenesis, fatty acid beta-oxidation and lipid metabolism (PubMed:29723273). May play a role in the circadian control of neutrophilic inflammation in the lung (PubMed:29533925). {ECO:0000269|PubMed:15623503, ECO:0000269|PubMed:18454201, ECO:0000269|PubMed:19682428, ECO:0000269|PubMed:22474260, ECO:0000269|PubMed:23221024, ECO:0000269|PubMed:23728303, ECO:0000269|PubMed:29355503, ECO:0000269|PubMed:29533925, ECO:0000269|PubMed:29723273}.
uniprot
proteins
mass_dalton
64302
uniprot
proteins
post_translational_modification
PTM: Deacetylated by HDAC1 (By similarity). Acetylation and deacetylation regulate its transcriptional regulatory activity (By similarity). {ECO:0000250|UniProtKB:Q14995}.; PTM: Under more reducing intracellular redox conditions, Cys-381 is in its heme-bound state, which is optimal for recruitment of the NCOR1/HDAC3 corepressor complex and repression of target genes (By similarity). When subjected to oxidative stress conditions, Cys-381 undergoes oxidation to form a disulfide bridge with Cys-371, also triggering a ligand switch that results in release of bound heme and derepression of target genes (By similarity). {ECO:0000250|UniProtKB:Q14995}.; PTM: Ubiquitinated by SIAH2; leading to its proteasomal degradation. {ECO:0000250|UniProtKB:Q14995}.; PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization. {ECO:0000269|PubMed:29533925}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
15623503
uniprot
proteins
pubmed
18454201
uniprot
proteins
pubmed
19682428
uniprot
proteins
pubmed
22474260
uniprot
proteins
pubmed
23221024
uniprot
proteins
pubmed
23728303
uniprot
proteins
pubmed
29355503
uniprot
proteins
pubmed
29508494
uniprot
proteins
pubmed
29533925
uniprot
proteins
pubmed
29723273
uniprot
proteins
pubmed
7838156
uniprot
proteins
pubmed
7838158
uniprot
proteins
sequence_length
576
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:29533925}. Cytoplasm {ECO:0000269|PubMed:29533925}. Note=Phosphorylation by CSNK1E enhances its cytoplasmic localization. {ECO:0000269|PubMed:29533925}.
uniprot
proteins