Nr1d2
entrez
259241
canonical
uniprot
Q63504
canonical
ensembl
ENSRNOG00000046912
resolver
ensembl
ENSRNOG00055014018
resolver
ensembl
ENSRNOG00060011268
resolver
ensembl
ENSRNOG00065011229
resolver
ensp
ENSRNOP00000075553
resolver
genesymbol
Nr1d2
resolver
uniprot
Q62756
resolver
uniprot
Q63542
resolver
uniprot_entry
NR1D2_RAT
resolver
uniprot_sec
Q62756
resolver
uniprot_sec
Q63542
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
MELNAGGVIAYISSSSSASSPASCHSEGSENSFQSSSSSVPSSPNSSNCDANGNPKNTDVSSIDGVLKSDRTDCPVKTGKPGAPGMTKSHSGMTKFSGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLIEMQSAMKTMMSTQFGGHLQSDTLAEPHEQSVPPAQEQLRPKPQLEQENIKSTPPPSDFAKEEVIGMVTRAHKDTFLYNQEHRENSSESMPPHRGERIPRNVEQYNLNHDHRGGGLHSHFPCSESQQHLSGQYKGRNMMHYPNGHTVCISNGHCVNFSSAYPQRVCDRIPVGGCSQTESRNSYLCSTGGRMHLVCPMSKSPYVDPQKSGHEIWEEFSMSFTPAVKEVVEFAKRIPGFRDLSQHDQVNLLKAGTFEVLMVRFASLFDAKERTVTFLSGKKYSVDDLHSMGAGDLLSSMFEFSEKLNGLQLSDEEMSLFTAVVLVSADRSGIENVNSVEALQETLIRALRTLIMKNHPNEASIFTKLLLKLPDLRSLNNMHSEELLAFKVHP
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 (By similarity). Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (By similarity). 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 (By similarity). May play a role in the circadian control of neutrophilic inflammation in the lung (By similarity). {ECO:0000250|UniProtKB:Q60674}.
uniprot
proteins
mass_dalton
64192
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-383 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-383 undergoes oxidation to form a disulfide bridge with Cys-373, 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:0000250|UniProtKB:Q60674}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
7945391
uniprot
proteins
pubmed
8747539
uniprot
proteins
sequence_length
578
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}. Cytoplasm {ECO:0000250|UniProtKB:Q60674}. Note=Phosphorylation by CSNK1E enhances its cytoplasmic localization. {ECO:0000250|UniProtKB:Q60674}.
uniprot
proteins