NR1D2_HUMAN
ID NR1D2_HUMAN Reviewed; 579 AA.
AC Q14995; B2R8Q3; O00402; Q86XD4;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 4.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Nuclear receptor subfamily 1 group D member 2 {ECO:0000305};
DE AltName: Full=Orphan nuclear hormone receptor BD73;
DE AltName: Full=Rev-erb alpha-related receptor;
DE Short=RVR;
DE AltName: Full=Rev-erb-beta;
DE AltName: Full=V-erbA-related protein 1-related;
DE Short=EAR-1R;
GN Name=NR1D2 {ECO:0000312|HGNC:HGNC:7963};
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].
RA Kamizono A., Shuichiro K., Kohei U.;
RT "Isolation of a novel member of the thyroid/steroid hormone receptor
RT superfamily from human osteoblastic osteosarcoma HOS cell.";
RL Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-21; LYS-282 AND
RP ARG-288.
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-579.
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=7997240; DOI=10.1210/mend.8.8.7997240;
RA Dumas B., Harding H.P., Choi H.-S., Lehmann K.A., Chung M., Lazar M.A.,
RA Moore D.D.;
RT "A new orphan member of the nuclear hormone receptor superfamily closely
RT related to Rev-Erb.";
RL Mol. Endocrinol. 8:996-1005(1994).
RN [6]
RP INTERACTION WITH NCOA5.
RX PubMed=11113208; DOI=10.1128/mcb.21.1.343-353.2001;
RA Sauve F., McBroom L.D.B., Gallant J., Moraitis A.N., Labrie F., Giguere V.;
RT "CIA, a novel estrogen receptor coactivator with a bifunctional nuclear
RT receptor interacting determinant.";
RL Mol. Cell. Biol. 21:343-353(2001).
RN [7]
RP FUNCTION, INTERACTION WITH ZNHIT1, AND SUBCELLULAR LOCATION.
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 [8]
RP FUNCTION, INTERACTION WITH KAT5 AND HDAC1, SUBCELLULAR LOCATION, AND
RP ACETYLATION AT LYS-162 AND LYS-163.
RX PubMed=17996965; DOI=10.1016/j.bbamcr.2007.09.004;
RA Wang J., Liu N., Liu Z., Li Y., Song C., Yuan H., Li Y.Y., Zhao X., Lu H.;
RT "The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to
RT regulate apolipoprotein CIII promoter.";
RL Biochim. Biophys. Acta 1783:224-236(2008).
RN [9]
RP HEME-BINDING, AND DISULFIDE BONDS.
RX PubMed=21123168; DOI=10.1074/jbc.m110.193466;
RA Gupta N., Ragsdale S.W.;
RT "Thiol-disulfide redox dependence of heme binding and heme ligand switching
RT in nuclear hormone receptor rev-erb{beta}.";
RL J. Biol. Chem. 286:4392-4403(2011).
RN [10]
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 [11]
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 [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 386-579, AND SUBUNIT.
RX PubMed=17870090; DOI=10.1016/j.jmb.2007.08.037;
RA Woo E.-J., Jeong D.G., Lim M.-Y., Jun Kim S., Kim K.-J., Yoon S.-M.,
RA Park B.-C., Eon Ryu S.;
RT "Structural insight into the constitutive repression function of the
RT nuclear receptor Rev-erbbeta.";
RL J. Mol. Biol. 373:735-744(2007).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 381-579, HEME-BINDING, AND
RP ACTIVITY REGULATION.
RX PubMed=19243223; DOI=10.1371/journal.pbio.1000043;
RA Pardee K.I., Xu X., Reinking J., Schuetz A., Dong A., Liu S., Zhang R.,
RA Tiefenbach J., Lajoie G., Plotnikov A.N., Botchkarev A., Krause H.M.,
RA Edwards A.;
RT "The structural basis of gas-responsive transcription by the human nuclear
RT hormone receptor REV-ERBbeta.";
RL PLoS Biol. 7:E43-E43(2009).
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 ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic
CC functions, including lipid metabolism and the inflammatory response.
CC Acts as a receptor for heme which stimulates its interaction with the
CC NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression.
CC Recognizes two classes of DNA response elements within the promoter of
CC its target genes and can bind to DNA as either monomers or homodimers,
CC depending on the nature of the response element. Binds as a monomer to
CC a response element composed of the consensus half-site motif 5'-
CC [A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a
CC homodimer to a direct repeat of the core motif spaced by two
CC nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR
CC alpha (RORA) function and also negatively regulates the expression of
CC NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle
CC via repression of genes involved in lipid metabolism and myogenesis
CC including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic
CC lipid metabolism via the repression of APOC3. Represses gene expression
CC at a distance in macrophages by inhibiting the transcription of
CC enhancer-derived RNAs (eRNAs). In addition to its activity as a
CC repressor, can also act as a transcriptional activator. Acts as a
CC transcriptional activator of the sterol regulatory element-binding
CC protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in
CC the skeletal muscle (By similarity). Plays a role in the regulation of
CC circadian sleep/wake cycle; essential for maintaining wakefulness
CC during the dark phase or active period (By similarity). Key regulator
CC of skeletal muscle mitochondrial function; negatively regulates the
CC skeletal muscle expression of core clock genes and genes involved in
CC mitochondrial biogenesis, fatty acid beta-oxidation and lipid
CC metabolism (By similarity). May play a role in the circadian control of
CC neutrophilic inflammation in the lung (By similarity).
CC {ECO:0000250|UniProtKB:Q60674, ECO:0000269|PubMed:17892483,
CC ECO:0000269|PubMed:17996965}.
CC -!- ACTIVITY REGULATION: The heme-bound form can bind gaseous signaling
CC molecules such as CO and nitric oxide (NO) and NO can reverse its
CC transcriptional repressor activity. {ECO:0000269|PubMed:19243223}.
CC -!- SUBUNIT: Binds DNA as a monomer or a homodimer (PubMed:17870090).
CC Interacts with NCOA5 coactivator, leading to a strong increase of
CC transcription of target genes (PubMed:11113208). Interacts (via N-
CC terminus) with KAT5 (PubMed:17996965). Interacts (via C-terminus) with
CC HDAC1 (PubMed:17996965). Interacts with ZNHIT1 (PubMed:17892483).
CC Interacts with SIAH2 (PubMed:26392558). {ECO:0000269|PubMed:11113208,
CC ECO:0000269|PubMed:17870090, ECO:0000269|PubMed:17892483,
CC ECO:0000269|PubMed:17996965, ECO:0000269|PubMed:26392558}.
CC -!- INTERACTION:
CC Q14995; G5E9A7: DMWD; NbExp=3; IntAct=EBI-6144053, EBI-10976677;
CC Q14995; P22607: FGFR3; NbExp=3; IntAct=EBI-6144053, EBI-348399;
CC Q14995; O15354: GPR37; NbExp=3; IntAct=EBI-6144053, EBI-15639515;
CC Q14995; P28799: GRN; NbExp=3; IntAct=EBI-6144053, EBI-747754;
CC Q14995; P28799-2: GRN; NbExp=3; IntAct=EBI-6144053, EBI-25860013;
CC Q14995; P06396: GSN; NbExp=3; IntAct=EBI-6144053, EBI-351506;
CC Q14995; P04792: HSPB1; NbExp=3; IntAct=EBI-6144053, EBI-352682;
CC Q14995; O60333-2: KIF1B; NbExp=3; IntAct=EBI-6144053, EBI-10975473;
CC Q14995; I6L9F6: NEFL; NbExp=3; IntAct=EBI-6144053, EBI-10178578;
CC Q14995; D3DTS7: PMP22; NbExp=3; IntAct=EBI-6144053, EBI-25882629;
CC Q14995; Q96LA8: PRMT6; NbExp=2; IntAct=EBI-6144053, EBI-912440;
CC Q14995; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-6144053, EBI-396669;
CC Q14995; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-6144053, EBI-5235340;
CC Q14995; Q86WV8: TSC1; NbExp=3; IntAct=EBI-6144053, EBI-12806590;
CC Q14995; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-6144053, EBI-741480;
CC Q14995; O76024: WFS1; NbExp=3; IntAct=EBI-6144053, EBI-720609;
CC Q14995; Q9Y649; NbExp=3; IntAct=EBI-6144053, EBI-25900580;
CC Q14995; O08785: Clock; Xeno; NbExp=2; IntAct=EBI-6144053, EBI-79859;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:17892483, ECO:0000269|PubMed:17996965}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q60674}. Note=Phosphorylation by CSNK1E enhances
CC its cytoplasmic localization. {ECO:0000250|UniProtKB:Q60674}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at high levels in the
CC liver, adipose tissue, skeletal muscle and brain. Expression oscillates
CC diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as
CC well as in peripheral tissues.
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: Deacetylated by HDAC1. Acetylation and deacetylation regulate its
CC transcriptional regulatory activity. {ECO:0000269|PubMed:17996965}.
CC -!- PTM: Under more reducing intracellular redox conditions, Cys-384 is in
CC its heme-bound state, which is optimal for recruitment of the
CC NCOR1/HDAC3 corepressor complex and repression of target genes. When
CC subjected to oxidative stress conditions, Cys-384 undergoes oxidation
CC to form a disulfide bridge with Cys-374, also triggering a ligand
CC switch that results in release of bound heme and derepression of target
CC genes. {ECO:0000269|PubMed:21123168}.
CC -!- PTM: Ubiquitinated by SIAH2; leading to proteasomal degradation.
CC {ECO:0000269|PubMed:26392558}.
CC -!- PTM: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic
CC localization. {ECO:0000250|UniProtKB:Q60674}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; D16815; BAA20088.1; -; mRNA.
DR EMBL; AK313464; BAG36250.1; -; mRNA.
DR EMBL; AC124914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC045613; AAH45613.1; -; mRNA.
DR EMBL; L31785; AAA65937.1; -; mRNA.
DR CCDS; CCDS33718.1; -.
DR PIR; A57057; A57057.
DR RefSeq; NP_005117.3; NM_005126.4.
DR PDB; 2V0V; X-ray; 2.40 A; A/B/C/D=387-579.
DR PDB; 2V7C; X-ray; 2.40 A; A/B=387-579.
DR PDB; 3CQV; X-ray; 1.90 A; A=381-579.
DR PDB; 4N73; X-ray; 1.87 A; A=381-578.
DR PDB; 6WMQ; X-ray; 2.55 A; A/B=381-579.
DR PDB; 6WMS; X-ray; 2.00 A; A/B=381-579.
DR PDBsum; 2V0V; -.
DR PDBsum; 2V7C; -.
DR PDBsum; 3CQV; -.
DR PDBsum; 4N73; -.
DR PDBsum; 6WMQ; -.
DR PDBsum; 6WMS; -.
DR AlphaFoldDB; Q14995; -.
DR SMR; Q14995; -.
DR BioGRID; 115299; 57.
DR IntAct; Q14995; 25.
DR MINT; Q14995; -.
DR STRING; 9606.ENSP00000310006; -.
DR BindingDB; Q14995; -.
DR ChEMBL; CHEMBL1961784; -.
DR DrugBank; DB14013; SR-9009.
DR DrugBank; DB14014; SR-9011.
DR GuidetoPHARMACOLOGY; 597; -.
DR iPTMnet; Q14995; -.
DR PhosphoSitePlus; Q14995; -.
DR BioMuta; NR1D2; -.
DR DMDM; 215274122; -.
DR EPD; Q14995; -.
DR jPOST; Q14995; -.
DR MassIVE; Q14995; -.
DR MaxQB; Q14995; -.
DR PaxDb; Q14995; -.
DR PeptideAtlas; Q14995; -.
DR PRIDE; Q14995; -.
DR ProteomicsDB; 60285; -.
DR ABCD; Q14995; 2 sequenced antibodies.
DR Antibodypedia; 11385; 343 antibodies from 31 providers.
DR DNASU; 9975; -.
DR Ensembl; ENST00000312521.9; ENSP00000310006.3; ENSG00000174738.13.
DR GeneID; 9975; -.
DR KEGG; hsa:9975; -.
DR MANE-Select; ENST00000312521.9; ENSP00000310006.3; NM_005126.5; NP_005117.3.
DR UCSC; uc003ccs.2; human.
DR CTD; 9975; -.
DR DisGeNET; 9975; -.
DR GeneCards; NR1D2; -.
DR HGNC; HGNC:7963; NR1D2.
DR HPA; ENSG00000174738; Low tissue specificity.
DR MIM; 602304; gene.
DR neXtProt; NX_Q14995; -.
DR OpenTargets; ENSG00000174738; -.
DR PharmGKB; PA31749; -.
DR VEuPathDB; HostDB:ENSG00000174738; -.
DR eggNOG; KOG4846; Eukaryota.
DR GeneTree; ENSGT00940000155168; -.
DR HOGENOM; CLU_007368_2_4_1; -.
DR InParanoid; Q14995; -.
DR OrthoDB; 1240230at2759; -.
DR PhylomeDB; Q14995; -.
DR TreeFam; TF328382; -.
DR PathwayCommons; Q14995; -.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR SignaLink; Q14995; -.
DR SIGNOR; Q14995; -.
DR BioGRID-ORCS; 9975; 14 hits in 1103 CRISPR screens.
DR ChiTaRS; NR1D2; human.
DR EvolutionaryTrace; Q14995; -.
DR GeneWiki; Rev-ErbA_beta; -.
DR GenomeRNAi; 9975; -.
DR Pharos; Q14995; Tchem.
DR PRO; PR:Q14995; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q14995; protein.
DR Bgee; ENSG00000174738; Expressed in calcaneal tendon and 209 other tissues.
DR ExpressionAtlas; Q14995; baseline and differential.
DR Genevisible; Q14995; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA: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; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048512; P:circadian behavior; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA: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:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:2001014; P:regulation of skeletal muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR DisProt; DP02702; -.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
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; Cytoplasm;
KW Disulfide bond; DNA-binding; Heme; Iron; Metal-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..579
FT /note="Nuclear receptor subfamily 1 group D member 2"
FT /id="PRO_0000053501"
FT DOMAIN 369..579
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 100..176
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 103..123
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 140..164
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..99
FT /note="Modulating"
FT REGION 1..60
FT /note="Required for phosphorylation by CSNK1E and
FT cytoplasmic localization"
FT /evidence="ECO:0000250|UniProtKB:Q60674"
FT REGION 13..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..250
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..579
FT /note="Interaction with ZNHIT1"
FT /evidence="ECO:0000269|PubMed:17892483"
FT COMPBIAS 13..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 384
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT BINDING 568
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT MOD_RES 46
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250"
FT MOD_RES 162
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000269|PubMed:17996965"
FT MOD_RES 163
FT /note="N6-acetyllysine; by KAT5"
FT /evidence="ECO:0000269|PubMed:17996965"
FT DISULFID 337..343
FT /evidence="ECO:0000269|PubMed:21123168"
FT DISULFID 374..384
FT /evidence="ECO:0000269|PubMed:21123168"
FT VARIANT 21
FT /note="P -> H (in dbSNP:rs17854365)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047377"
FT VARIANT 282
FT /note="Q -> K (in dbSNP:rs17857305)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047378"
FT VARIANT 288
FT /note="P -> R (in dbSNP:rs17857306)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047379"
FT VARIANT 386
FT /note="M -> L (in dbSNP:rs4858097)"
FT /id="VAR_047380"
FT CONFLICT 519..520
FT /note="IE -> NRK (in Ref. 5; AAA65937)"
FT /evidence="ECO:0000305"
FT HELIX 398..420
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 424..428
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 431..449
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:4N73"
FT TURN 456..459
FT /evidence="ECO:0007829|PDB:4N73"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:4N73"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 471..476
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 481..495
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 500..512
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:2V0V"
FT HELIX 522..543
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 549..573
FT /evidence="ECO:0007829|PDB:4N73"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:6WMQ"
SQ SEQUENCE 579 AA; 64643 MW; 38F82863D7F8E00F CRC64;
MEVNAGGVIA YISSSSSASS PASCHSEGSE NSFQSSSSSV PSSPNSSNSD TNGNPKNGDL
ANIEGILKND RIDCSMKTSK SSAPGMTKSH SGVTKFSGMV LLCKVCGDVA SGFHYGVHAC
EGCKGFFRRS IQQNIQYKKC LKNENCSIMR MNRNRCQQCR FKKCLSVGMS RDAVRFGRIP
KREKQRMLIE MQSAMKTMMN SQFSGHLQND TLVEHHEQTA LPAQEQLRPK PQLEQENIKS
SSPPSSDFAK EEVIGMVTRA HKDTFMYNQE QQENSAESMQ PQRGERIPKN MEQYNLNHDH
CGNGLSSHFP CSESQQHLNG QFKGRNIMHY PNGHAICIAN GHCMNFSNAY TQRVCDRVPI
DGFSQNENKN SYLCNTGGRM HLVCPMSKSP YVDPHKSGHE IWEEFSMSFT PAVKEVVEFA
KRIPGFRDLS QHDQVNLLKA GTFEVLMVRF ASLFDAKERT VTFLSGKKYS VDDLHSMGAG
DLLNSMFEFS EKLNALQLSD EEMSLFTAVV LVSADRSGIE NVNSVEALQE TLIRALRTLI
MKNHPNEASI FTKLLLKLPD LRSLNNMHSE ELLAFKVHP
