Nr1d1
entrez
217166
canonical
uniprot
Q3UV55
canonical
ensembl
ENSMUSG00000020889
resolver
ensp
ENSMUSP00000069505
resolver
enst
ENSMUST00000064941
resolver
genesymbol
Nr1d1
resolver
genesymbol_syn
Ear1
resolver
uniprot
Q3UJJ1
resolver
uniprot
Q62171
resolver
uniprot
Q6EEZ6
resolver
uniprot
Q922A5
resolver
uniprot
Q9ESY4
resolver
uniprot_entry
NR1D1_MOUSE
resolver
uniprot_sec
Q3UJJ1
resolver
uniprot_sec
Q62171
resolver
uniprot_sec
Q6EEZ6
resolver
uniprot_sec
Q922A5
resolver
uniprot_sec
Q9ESY4
resolver
amino_acid_sequence
MTTLDSNNNTGGVITYIGSSGSSPSRTSPESLYSDSSNGSFQSLTQGCPTYFPPSPTGSLTQDPARSFGSAPPSLSDDSSPSSASSSSSSSSSSFYNGSPPGSLQVAMEDSSRVSPSKGTSNITKLNGMVLLCKVCGDVASGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRINRNRCQQCRFKKCLSVGMSRDAVRFGRIPKREKQRMLAEMQSAMNLANNQLSSLCPLETSPTPHPTSGSMGPSPPPAPAPTPLVGFSQFPQQLTPPRSPSPEPTMEDVISQVARAHREIFTYAHDKLGTSPGNFNANHASGSPSATTPHRWESQGCPSAPNDNNLLAAQRHNEALNGLRQGPSSYPPTWPSGPTHHSCHQPNSNGHRLCPTHVYSAPEGEAPANSLRQGNTKNVLLACPMNMYPHGRSGRTVQEIWEDFSMSFTPAVREVVEFAKHIPGFRDLSQHDQVTLLKAGTFEVLMVRFASLFNVKDQTVMFLSRTTYSLQELGAMGMGDLLNAMFDFSEKLNSLALTEEELGLFTAVVLVSADRSGMENSASVEQLQETLLRALRALVLKNRPSETSRFTKLLLKLPDLRTLNNMHSEKLLSFRVDAQ
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, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage 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 nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (PubMed:30555544). Represses the transcription of CES2 (PubMed:29653076). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (PubMed:24794873). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (PubMed:27686098). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (PubMed:29533925). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (PubMed:30792350). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (PubMed:30096135). {ECO:0000269|PubMed:18227153, ECO:0000269|PubMed:18454201, ECO:0000269|PubMed:18565334, ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:19721697, ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:21408158, ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:22166979, ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:22474260, ECO:0000269|PubMed:22549838, ECO:0000269|PubMed:23201262, ECO:0000269|PubMed:23728303, ECO:0000269|PubMed:23852339, ECO:0000269|PubMed:23936124, ECO:0000269|PubMed:24030830, ECO:0000269|PubMed:24162845, ECO:0000269|PubMed:24794873, ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29533925, ECO:0000269|PubMed:29653076, ECO:0000269|PubMed:30096135, ECO:0000269|PubMed:30555544, ECO:0000269|PubMed:30792350, ECO:0000269|PubMed:31748741}.
uniprot
proteins
mass_dalton
66802
uniprot
proteins
mutagenesis
MUTAGEN 275; /note="T->A: Loss of interaction with FBXW7 and loss of CDK1-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:27238018"; MUTAGEN 279; /note="S->A: Loss of interaction with FBXW7."; /evidence="ECO:0000269|PubMed:27238018"; MUTAGEN 456; /note="K->A: Reduces interaction with PER2 by 60%."; /evidence="ECO:0000269|PubMed:20159955
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated, leading to its proteasomal degradation (PubMed:20534529). Ubiquitinated by the SCF(FBXW7) complex when phosphorylated by CDK1 leading to its proteasomal degradation (PubMed:27238018). Ubiquitinated by SIAH2; leading to its proteasomal degradation (By similarity). Rapidly ubiquitinated in response to inflammatory triggers and sumoylation is a prerequisite to its ubiquitination (PubMed:29533925). {ECO:0000250|UniProtKB:P20393, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:29533925}.; PTM: Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a prerequisite to its ubiquitination. {ECO:0000269|PubMed:29533925}.; PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization. {ECO:0000269|PubMed:29508494}.; PTM: Undergoes lysosome-mediated degradation in a time-dependent manner in the liver. {ECO:0000269|PubMed:29937374}.
uniprot
proteins
protein_family
NR1 subfamily
uniprot
proteins
protein_family
Nuclear hormone receptor family
uniprot
proteins
pubmed
14645221
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15591021
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
18227153
uniprot
proteins
pubmed
18454201
uniprot
proteins
pubmed
18565334
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19710360
uniprot
proteins
pubmed
19721697
uniprot
proteins
pubmed
20159955
uniprot
proteins
pubmed
20534529
uniprot
proteins
pubmed
21408158
uniprot
proteins
pubmed
21874017
uniprot
proteins
pubmed
22166979
uniprot
proteins
pubmed
22170608
uniprot
proteins
pubmed
22184247
uniprot
proteins
pubmed
22474260
uniprot
proteins
pubmed
22549838
uniprot
proteins
pubmed
23201262
uniprot
proteins
pubmed
23398316
uniprot
proteins
pubmed
23531614
uniprot
proteins
pubmed
23728303
uniprot
proteins
pubmed
23852339
uniprot
proteins
pubmed
23936124
uniprot
proteins
pubmed
24030830
uniprot
proteins
pubmed
24162845
uniprot
proteins
pubmed
24603368
uniprot
proteins
pubmed
24794873
uniprot
proteins
pubmed
25212631
uniprot
proteins
pubmed
27238018
uniprot
proteins
pubmed
27686098
uniprot
proteins
pubmed
29508494
uniprot
proteins
pubmed
29533925
uniprot
proteins
pubmed
29653076
uniprot
proteins
pubmed
29937374
uniprot
proteins
pubmed
30096135
uniprot
proteins
pubmed
30555544
uniprot
proteins
pubmed
30792350
uniprot
proteins
pubmed
31748741
uniprot
proteins
pubmed
9405624
uniprot
proteins
sequence_length
615
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407, ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29508494}. Cytoplasm {ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29508494}. Cell projection, dendrite {ECO:0000269|PubMed:21874017}. Cell projection, dendritic spine {ECO:0000269|PubMed:21874017}. Note=Localizes to the cytoplasm, dendrites and dendritic spine in the presence of OPHN1 (PubMed:21874017). Localizes predominantly to the nucleus at ZT8 whereas it is cytoplasmic at ZT20 (PubMed:27686098). Phosphorylation by CSNK1E enhances its cytoplasmic localization (PubMed:29508494). {ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:29508494}.
uniprot
proteins