NR1D1_HUMAN
ID NR1D1_HUMAN Reviewed; 614 AA.
AC P20393; Q0P5Z4; Q15304;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Nuclear receptor subfamily 1 group D member 1;
DE AltName: Full=Rev-erbA-alpha;
DE AltName: Full=V-erbA-related protein 1;
DE Short=EAR-1;
GN Name=NR1D1; Synonyms=EAR1, HREV, THRAL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=2539258; DOI=10.1016/0092-8674(89)90169-4;
RA Miyajima N., Horiuchi R., Shibuya Y., Fukushige S., Matsubara K.,
RA Toyoshima K., Yamamoto T.;
RT "Two erbA homologs encoding proteins with different T3 binding capacities
RT are transcribed from opposite DNA strands of the same genetic locus.";
RL Cell 57:31-39(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Fetal skeletal muscle;
RX PubMed=1971514; DOI=10.1089/dna.1990.9.77;
RA Lazar M.A., Jones K.E., Chin W.W.;
RT "Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the
RT noncoding DNA strand of a thyroid hormone receptor gene results in a
RT related protein that does not bind thyroid hormone.";
RL DNA Cell Biol. 9:77-83(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 549-614.
RX PubMed=1850510; DOI=10.1093/nar/19.5.1105;
RA Laudet V., Begue A., Henry C., Joubel A., Martin P., Stehelin D., Saule S.;
RT "Genomic organization of the human thyroid hormone receptor alpha (c-erbA-
RT 1) gene.";
RL Nucleic Acids Res. 19:1105-1112(1991).
RN [5]
RP FUNCTION.
RX PubMed=12021280; DOI=10.1074/jbc.m203421200;
RA Coste H., Rodriguez J.C.;
RT "Orphan nuclear hormone receptor Rev-erbalpha regulates the human
RT apolipoprotein CIII promoter.";
RL J. Biol. Chem. 277:27120-27129(2002).
RN [6]
RP FUNCTION.
RX PubMed=15761026; DOI=10.1210/me.2005-0057;
RA Yin L., Lazar M.A.;
RT "The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone
RT deacetylase 3 corepressor to regulate the circadian Bmal1 gene.";
RL Mol. Endocrinol. 19:1452-1459(2005).
RN [7]
RP FUNCTION.
RX PubMed=16968709; DOI=10.1074/jbc.m607873200;
RA Wang J., Yin L., Lazar M.A.;
RT "The orphan nuclear receptor Rev-erb alpha regulates circadian expression
RT of plasminogen activator inhibitor type 1.";
RL J. Biol. Chem. 281:33842-33848(2006).
RN [8]
RP PHOSPHORYLATION AT SER-55 AND SER-59, AND UBIQUITINATION.
RX PubMed=16484495; DOI=10.1126/science.1121613;
RA Yin L., Wang J., Klein P.S., Lazar M.A.;
RT "Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of
RT the circadian clock.";
RL Science 311:1002-1005(2006).
RN [9]
RP INTERACTION WITH ZNHIT1.
RX PubMed=17892483; DOI=10.1111/j.1742-4658.2007.06062.x;
RA Wang J., Li Y., Zhang M., Liu Z., Wu C., Yuan H., Li Y.Y., Zhao X., Lu H.;
RT "A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with
RT orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced
RT inhibition of apoCIII transcription.";
RL FEBS J. 274:5370-5381(2007).
RN [10]
RP FUNCTION, AND HEME-BINDING.
RX PubMed=18006707; DOI=10.1126/science.1150179;
RA Yin L., Wu N., Curtin J.C., Qatanani M., Szwergold N.R., Reid R.A.,
RA Waitt G.M., Parks D.J., Pearce K.H., Wisely G.B., Lazar M.A.;
RT "Rev-erbalpha, a heme sensor that coordinates metabolic and circadian
RT pathways.";
RL Science 318:1786-1789(2007).
RN [11]
RP FUNCTION.
RX PubMed=19710360; DOI=10.1101/gad.1825809;
RA Wu N., Yin L., Hanniman E.A., Joshi S., Lazar M.A.;
RT "Negative feedback maintenance of heme homeostasis by its receptor, Rev-
RT erbalpha.";
RL Genes Dev. 23:2201-2209(2009).
RN [12]
RP REVIEW.
RX PubMed=20414452; DOI=10.1621/nrs.08001;
RA Yin L., Wu N., Lazar M.A.;
RT "Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian
RT rhythm and metabolism.";
RL Nucl. Recept. Signal. 8:E001-E001(2010).
RN [13]
RP INTERACTION WITH HUWE1, AND UBIQUITINATION AND PROTEASOMAL DEGRADATION.
RX PubMed=20534529; DOI=10.1073/pnas.1000438107;
RA Yin L., Joshi S., Wu N., Tong X., Lazar M.A.;
RT "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the
RT circadian heme receptor Rev-erb alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11614-11619(2010).
RN [14]
RP INTERACTION WITH OPHN1.
RX PubMed=21874017; DOI=10.1038/nn.2911;
RA Valnegri P., Khelfaoui M., Dorseuil O., Bassani S., Lagneaux C.,
RA Gianfelice A., Benfante R., Chelly J., Billuart P., Sala C., Passafaro M.;
RT "A circadian clock in hippocampus is regulated by interaction between
RT oligophrenin-1 and Rev-erbalpha.";
RL Nat. Neurosci. 14:1293-1301(2011).
RN [15]
RP INTERACTION WITH CRY1 AND PER2.
RX PubMed=22170608; DOI=10.1038/nature10700;
RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W.,
RA Downes M., Evans R.M.;
RT "Cryptochromes mediate rhythmic repression of the glucocorticoid
RT receptor.";
RL Nature 480:552-556(2011).
RN [16]
RP FUNCTION.
RX PubMed=21479263; DOI=10.1371/journal.pone.0017290;
RA Crumbley C., Burris T.P.;
RT "Direct regulation of CLOCK expression by REV-ERB.";
RL PLoS ONE 6:E17290-E17290(2011).
RN [17]
RP REVIEW.
RX PubMed=22682217; DOI=10.1016/j.cmet.2012.05.006;
RA Stratmann M., Schibler U.;
RT "REV-ERBs: more than the sum of the individual parts.";
RL Cell Metab. 15:791-793(2012).
RN [18]
RP REVIEW.
RX PubMed=22613952; DOI=10.1038/cr.2012.81;
RA Ripperger J.A., Albrecht U.;
RT "REV-ERB-erating nuclear receptor functions in circadian metabolism and
RT physiology.";
RL Cell Res. 22:1319-1321(2012).
RN [19]
RP FUNCTION.
RX PubMed=22184247; DOI=10.1073/pnas.1106750109;
RA Gibbs J.E., Blaikley J., Beesley S., Matthews L., Simpson K.D., Boyce S.H.,
RA Farrow S.N., Else K.J., Singh D., Ray D.W., Loudon A.S.;
RT "The nuclear receptor REV-ERBalpha mediates circadian regulation of innate
RT immunity through selective regulation of inflammatory cytokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:582-587(2012).
RN [20]
RP FUNCTION, INTERACTION WITH CCAR2, PHOSPHORYLATION AT SER-55 AND SER-59, AND
RP UBIQUITINATION.
RX PubMed=23398316; DOI=10.1042/bj20121085;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of
RT the nuclear receptor Rev-erbalpha.";
RL Biochem. J. 451:453-461(2013).
RN [21]
RP ACETYLATION AT LYS-400 AND LYS-591.
RX PubMed=24415752; DOI=10.1074/jbc.m113.512913;
RA Nin V., Chini C.C., Escande C., Capellini V., Chini E.N.;
RT "Deleted in breast cancer 1 (DBC1) protein regulates hepatic
RT gluconeogenesis.";
RL J. Biol. Chem. 289:5518-5527(2014).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP UBIQUITINATION, PROTEASOMAL DEGRADATION, AND INTERACTION WITH SIAH2.
RX PubMed=26392558; DOI=10.1073/pnas.1501204112;
RA DeBruyne J.P., Baggs J.E., Sato T.K., Hogenesch J.B.;
RT "Ubiquitin ligase Siah2 regulates RevErbalpha degradation and the mammalian
RT circadian clock.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:12420-12425(2015).
RN [24]
RP INTERACTION WITH FBXW7.
RX PubMed=27238018; DOI=10.1016/j.cell.2016.05.012;
RA Zhao X., Hirota T., Han X., Cho H., Chong L.W., Lamia K., Liu S.,
RA Atkins A.R., Banayo E., Liddle C., Yu R.T., Yates J.R. III, Kay S.A.,
RA Downes M., Evans R.M.;
RT "Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha
RT degradation.";
RL Cell 165:1644-1657(2016).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 123-215, AND SUBUNIT.
RX PubMed=9660968; DOI=10.1016/s1097-2765(00)80084-2;
RA Zhao Q., Khorasanizadeh S., Miyoshi Y., Lazar M.A., Rastinejad F.;
RT "Structural elements of an orphan nuclear receptor-DNA complex.";
RL Mol. Cell 1:849-861(1998).
CC -!- FUNCTION: Transcriptional repressor which coordinates circadian rhythm
CC and metabolic pathways in a heme-dependent manner. Integral component
CC of the complex transcription machinery that governs circadian
CC rhythmicity and forms a critical negative limb of the circadian clock
CC by directly repressing the expression of core clock components
CC ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic
CC functions, including lipid and bile acid metabolism, adipogenesis,
CC gluconeogenesis and the macrophage inflammatory response. Acts as a
CC receptor for heme which stimulates its interaction with the NCOR1/HDAC3
CC corepressor complex, enhancing transcriptional repression. Recognizes
CC two classes of DNA response elements within the promoter of its target
CC genes and can bind to DNA as either monomers or homodimers, depending
CC on the nature of the response element. Binds as a monomer to a response
CC element composed of the consensus half-site motif 5'-[A/G]GGTCA-3'
CC preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a
CC direct repeat of the core motif spaced by two nucleotides (RevDR-2).
CC Acts as a potent competitive repressor of ROR alpha (RORA) function and
CC regulates the levels of its ligand heme by repressing the expression of
CC PPARGC1A, a potent inducer of heme synthesis. Regulates lipid
CC metabolism by repressing the expression of APOC3 and by influencing the
CC activity of sterol response element binding proteins (SREBPs);
CC represses INSIG2 which interferes with the proteolytic activation of
CC SREBPs which in turn govern the rhythmic expression of enzymes with key
CC functions in sterol and fatty acid synthesis. Regulates gluconeogenesis
CC via repression of G6PC1 and PEPCK and adipocyte differentiation via
CC repression of PPARG. Regulates glucagon release in pancreatic alpha-
CC cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-
CC induced insulin secretion and expression of key lipogenic genes in
CC pancreatic-beta cells. Positively regulates bile acid synthesis by
CC increasing hepatic expression of CYP7A1 via repression of NR0B2 and
CC NFIL3 which are negative regulators of CYP7A1. Modulates skeletal
CC muscle oxidative capacity by regulating mitochondrial biogenesis and
CC autophagy; controls mitochondrial biogenesis and respiration by
CC interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway.
CC Represses the expression of SERPINE1/PAI1, an important modulator of
CC cardiovascular disease and the expression of inflammatory cytokines and
CC chemokines in macrophages. Represses gene expression at a distance in
CC macrophages by inhibiting the transcription of enhancer-derived RNAs
CC (eRNAs). Plays a role in the circadian regulation of body temperature
CC and negatively regulates thermogenic transcriptional programs in brown
CC adipose tissue (BAT); imposes a circadian oscillation in BAT activity,
CC increasing body temperature when awake and depressing thermogenesis
CC during sleep. In concert with NR2E3, regulates transcriptional networks
CC critical for photoreceptor development and function. In addition to its
CC activity as a repressor, can also act as a transcriptional activator.
CC In the ovarian granulosa cells acts as a transcriptional activator of
CC STAR which plays a role in steroid biosynthesis. In collaboration with
CC SP1, activates GJA1 transcription in a heme-independent manner.
CC Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By
CC similarity). Represses the transcription of CES2 (By similarity).
CC Represses and regulates the circadian expression of TSHB in a NCOR1-
CC dependent manner (By similarity). Negatively regulates the protein
CC stability of NR3C1 and influences the time-dependent subcellular
CC distribution of NR3C1, thereby affecting its transcriptional regulatory
CC activity (By similarity). Plays a critical role in the circadian
CC control of neutrophilic inflammation in the lung; under resting, non-
CC stress conditions, acts as a rhythmic repressor to limit inflammatory
CC activity whereas in the presence of inflammatory triggers undergoes
CC ubiquitin-mediated degradation thereby relieving inhibition of the
CC inflammatory response (By similarity). Plays a key role in the
CC circadian regulation of microglial activation and neuroinflammation;
CC suppresses microglial activation through the NF-kappaB pathway in the
CC central nervous system (By similarity). Plays a role in the regulation
CC of the diurnal rhythms of lipid and protein metabolism in the skeletal
CC muscle via transcriptional repression of genes controlling lipid and
CC amino acid metabolism in the muscle (By similarity).
CC {ECO:0000250|UniProtKB:Q3UV55, ECO:0000269|PubMed:12021280,
CC ECO:0000269|PubMed:15761026, ECO:0000269|PubMed:16968709,
CC ECO:0000269|PubMed:18006707, ECO:0000269|PubMed:19710360,
CC ECO:0000269|PubMed:1971514, ECO:0000269|PubMed:21479263,
CC ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:23398316,
CC ECO:0000269|PubMed:2539258}.
CC -!- SUBUNIT: Binds DNA as a monomer or a homodimer (PubMed:9660968).
CC Interacts with C1D, NR2E3 and SP1 (By similarity). Interacts with OPHN1
CC (via C-terminus) (PubMed:21874017). Interacts with ZNHIT1
CC (PubMed:17892483). Interacts with PER2; the interaction associates PER2
CC to ARNTL promoter region (PubMed:22170608). Interacts with CRY1
CC (PubMed:22170608). Interacts with CCAR2 (PubMed:23398316). Interacts
CC with SIAH2 (PubMed:26392558). Interacts with CDK1 (By similarity).
CC Interacts with FBXW7 (PubMed:27238018). Interacts with HUWE1
CC (PubMed:20534529). Interacts with NR0B2 (By similarity). Interacts with
CC NFIL3 (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and
CC HSP90AB1 (By similarity). {ECO:0000250|UniProtKB:Q3UV55,
CC ECO:0000269|PubMed:17892483, ECO:0000269|PubMed:20534529,
CC ECO:0000269|PubMed:21874017, ECO:0000269|PubMed:22170608,
CC ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:26392558,
CC ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:9660968}.
CC -!- INTERACTION:
CC P20393; P06727: APOA4; NbExp=3; IntAct=EBI-2811738, EBI-1222447;
CC P20393; Q7Z6Z7: HUWE1; NbExp=3; IntAct=EBI-2811738, EBI-625934;
CC P20393; A0A0S2Z3X1: INPP1; NbExp=3; IntAct=EBI-2811738, EBI-16430606;
CC P20393; O75376: NCOR1; NbExp=3; IntAct=EBI-2811738, EBI-347233;
CC P20393; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-2811738, EBI-742688;
CC P20393; P48775: TDO2; NbExp=3; IntAct=EBI-2811738, EBI-743494;
CC P20393; O54943: Per2; Xeno; NbExp=2; IntAct=EBI-2811738, EBI-1266779;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q3UV55}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q3UV55}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q3UV55}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q3UV55}. Note=Localizes to the cytoplasm,
CC dendrites and dendritic spine in the presence of OPHN1. Localizes
CC predominantly to the nucleus at ZT8 whereas it is cytoplasmic at ZT20.
CC Phosphorylation by CSNK1E enhances its cytoplasmic localization.
CC {ECO:0000250|UniProtKB:Q3UV55}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high levels in the
CC liver, adipose tissue, skeletal muscle and brain. Also expressed in
CC endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and
CC macrophages. Expression oscillates diurnally in the suprachiasmatic
CC nucleus (SCN) of the hypothalamus as well as in peripheral tissues.
CC Expression increases during the differentiation of pre-adipocytes into
CC mature adipocytes. Expressed at high levels in some squamous carcinoma
CC cell lines. {ECO:0000269|PubMed:2539258}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation
CC (PubMed:16484495, PubMed:23398316, PubMed:20534529). Ubiquitinated by
CC SIAH2; leading to its proteasomal degradation (PubMed:26392558).
CC Ubiquitinated by the SCF(FBXW7) complex when phosphorylated by CDK1
CC leading to its proteasomal degradation (By similarity). Rapidly
CC ubiquitinated in response to inflammatory triggers and sumoylation is a
CC prerequisite to its ubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:Q3UV55, ECO:0000269|PubMed:16484495,
CC ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:23398316,
CC ECO:0000269|PubMed:26392558}.
CC -!- PTM: Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a
CC prerequisite to its ubiquitination. {ECO:0000250|UniProtKB:Q3UV55}.
CC -!- PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic
CC localization. {ECO:0000250|UniProtKB:Q3UV55}.
CC -!- PTM: Undergoes lysosome-mediated degradation in a time-dependent manner
CC in the liver. {ECO:0000250|UniProtKB:Q3UV55}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; M24898; AAA52335.1; -; mRNA.
DR EMBL; M24900; AAA52332.1; -; mRNA.
DR EMBL; X55066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X55067; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; X72631; CAB53540.1; -; mRNA.
DR EMBL; BC047875; AAH47875.1; -; mRNA.
DR EMBL; BC056148; AAH56148.1; -; mRNA.
DR EMBL; M34339; AAA36561.1; -; mRNA.
DR EMBL; M34340; AAA36562.2; -; mRNA.
DR CCDS; CCDS11361.1; -.
DR PIR; A32286; A32608.
DR RefSeq; NP_068370.1; NM_021724.4.
DR PDB; 1A6Y; X-ray; 2.30 A; A/B=123-216.
DR PDB; 1GA5; X-ray; 2.40 A; A/B/E/F=123-216.
DR PDB; 1HLZ; X-ray; 2.80 A; A/B=123-216.
DR PDB; 3N00; X-ray; 2.60 A; A=281-614.
DR PDBsum; 1A6Y; -.
DR PDBsum; 1GA5; -.
DR PDBsum; 1HLZ; -.
DR PDBsum; 3N00; -.
DR AlphaFoldDB; P20393; -.
DR SMR; P20393; -.
DR BioGRID; 114941; 22.
DR DIP; DIP-48396N; -.
DR IntAct; P20393; 15.
DR MINT; P20393; -.
DR STRING; 9606.ENSP00000246672; -.
DR BindingDB; P20393; -.
DR ChEMBL; CHEMBL1961783; -.
DR DrugBank; DB14013; SR-9009.
DR DrugBank; DB14014; SR-9011.
DR GuidetoPHARMACOLOGY; 596; -.
DR iPTMnet; P20393; -.
DR PhosphoSitePlus; P20393; -.
DR BioMuta; NR1D1; -.
DR DMDM; 119100; -.
DR EPD; P20393; -.
DR jPOST; P20393; -.
DR MassIVE; P20393; -.
DR MaxQB; P20393; -.
DR PaxDb; P20393; -.
DR PeptideAtlas; P20393; -.
DR PRIDE; P20393; -.
DR ProteomicsDB; 53759; -.
DR Antibodypedia; 16433; 505 antibodies from 36 providers.
DR DNASU; 9572; -.
DR Ensembl; ENST00000246672.4; ENSP00000246672.3; ENSG00000126368.6.
DR GeneID; 9572; -.
DR KEGG; hsa:9572; -.
DR MANE-Select; ENST00000246672.4; ENSP00000246672.3; NM_021724.5; NP_068370.1.
DR UCSC; uc002htz.4; human.
DR CTD; 9572; -.
DR DisGeNET; 9572; -.
DR GeneCards; NR1D1; -.
DR HGNC; HGNC:7962; NR1D1.
DR HPA; ENSG00000126368; Tissue enhanced (skin).
DR MIM; 602408; gene.
DR neXtProt; NX_P20393; -.
DR OpenTargets; ENSG00000126368; -.
DR PharmGKB; PA31748; -.
DR VEuPathDB; HostDB:ENSG00000126368; -.
DR eggNOG; KOG4846; Eukaryota.
DR GeneTree; ENSGT00940000160548; -.
DR HOGENOM; CLU_007368_2_4_1; -.
DR InParanoid; P20393; -.
DR OMA; LCPTHMY; -.
DR OrthoDB; 1240230at2759; -.
DR PhylomeDB; P20393; -.
DR TreeFam; TF328382; -.
DR PathwayCommons; P20393; -.
DR Reactome; R-HSA-1368071; NR1D1 (REV-ERBA) represses gene expression.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SignaLink; P20393; -.
DR SIGNOR; P20393; -.
DR BioGRID-ORCS; 9572; 15 hits in 1108 CRISPR screens.
DR ChiTaRS; NR1D1; human.
DR EvolutionaryTrace; P20393; -.
DR GeneWiki; Rev-ErbA_alpha; -.
DR GenomeRNAi; 9572; -.
DR Pharos; P20393; Tchem.
DR PRO; PR:P20393; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P20393; protein.
DR Bgee; ENSG00000126368; Expressed in skin of leg and 205 other tissues.
DR ExpressionAtlas; P20393; baseline and differential.
DR Genevisible; P20393; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0070888; F:E-box binding; IEA:Ensembl.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; TAS:ProtInc.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0060086; P:circadian temperature homeostasis; ISS:UniProtKB.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0061889; P:negative regulation of astrocyte activation; ISS:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:UniProtKB.
DR GO; GO:0150079; P:negative regulation of neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0070859; P:positive regulation of bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0042749; P:regulation of circadian sleep/wake cycle; ISS:UniProtKB.
DR GO; GO:0045598; P:regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; ISS:UniProtKB.
DR GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID00033; -.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Biological rhythms; Cell projection;
KW Cytoplasm; Differentiation; DNA-binding; Heme; Iron; Metal-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Repressor; Synapse;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..614
FT /note="Nuclear receptor subfamily 1 group D member 1"
FT /id="PRO_0000053499"
FT DOMAIN 284..614
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 129..205
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 132..152
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 169..193
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..128
FT /note="Modulating"
FT REGION 1..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..70
FT /note="Required for phosphorylation by CSNK1E and
FT cytoplasmic localization"
FT /evidence="ECO:0000250|UniProtKB:Q3UV55"
FT REGION 49..284
FT /note="Crucial for activation of GJA1"
FT /evidence="ECO:0000250"
FT REGION 233..285
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 311..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..263
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 311..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 418
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000250"
FT BINDING 602
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT MOD_RES 55
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:16484495,
FT ECO:0000269|PubMed:23398316"
FT MOD_RES 59
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:16484495,
FT ECO:0000269|PubMed:23398316"
FT MOD_RES 191
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000250"
FT MOD_RES 192
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000250"
FT MOD_RES 274
FT /note="Phosphothreonine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q3UV55"
FT MOD_RES 400
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:24415752"
FT MOD_RES 591
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:24415752"
FT CONFLICT 147
FT /note="H -> L (in Ref. 2; CAB53540)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="E -> Q (in Ref. 2)"
FT /evidence="ECO:0000305"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:1A6Y"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:1A6Y"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:1A6Y"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:1A6Y"
FT HELIX 150..160
FT /evidence="ECO:0007829|PDB:1A6Y"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:1GA5"
FT TURN 179..183
FT /evidence="ECO:0007829|PDB:1A6Y"
FT HELIX 186..193
FT /evidence="ECO:0007829|PDB:1A6Y"
FT TURN 194..197
FT /evidence="ECO:0007829|PDB:1A6Y"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:1GA5"
FT HELIX 285..299
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 434..456
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 465..486
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 509..511
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 514..529
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 534..546
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 556..577
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 584..589
FT /evidence="ECO:0007829|PDB:3N00"
FT HELIX 591..602
FT /evidence="ECO:0007829|PDB:3N00"
FT STRAND 606..610
FT /evidence="ECO:0007829|PDB:3N00"
SQ SEQUENCE 614 AA; 66805 MW; 67C71758E166508A CRC64;
MTTLDSNNNT GGVITYIGSS GSSPSRTSPE SLYSDNSNGS FQSLTQGCPT YFPPSPTGSL
TQDPARSFGS IPPSLSDDGS PSSSSSSSSS SSSFYNGSPP GSLQVAMEDS SRVSPSKSTS
NITKLNGMVL LCKVCGDVAS GFHYGVHACE GCKGFFRRSI QQNIQYKRCL KNENCSIVRI
NRNRCQQCRF KKCLSVGMSR DAVRFGRIPK REKQRMLAEM QSAMNLANNQ LSSQCPLETS
PTQHPTPGPM GPSPPPAPVP SPLVGFSQFP QQLTPPRSPS PEPTVEDVIS QVARAHREIF
TYAHDKLGSS PGNFNANHAS GSPPATTPHR WENQGCPPAP NDNNTLAAQR HNEALNGLRQ
APSSYPPTWP PGPAHHSCHQ SNSNGHRLCP THVYAAPEGK APANSPRQGN SKNVLLACPM
NMYPHGRSGR TVQEIWEDFS MSFTPAVREV VEFAKHIPGF RDLSQHDQVT LLKAGTFEVL
MVRFASLFNV KDQTVMFLSR TTYSLQELGA MGMGDLLSAM FDFSEKLNSL ALTEEELGLF
TAVVLVSADR SGMENSASVE QLQETLLRAL RALVLKNRPL ETSRFTKLLL KLPDLRTLNN
MHSEKLLSFR VDAQ
