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Protein

Nuclear receptor subfamily 1 group D member 1

Gene

Nr1d1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 ARTNL/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 G6PC 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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei419 – 4191HemeBy similarity
Binding sitei603 – 6031HemeBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi130 – 20677Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri133 – 15321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri170 – 19425NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor, Repressor

Keywords - Biological processi

Biological rhythms, Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Heme, Iron, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 1 group D member 1
Alternative name(s):
Rev-erbA-alpha
V-erbA-related protein 1
Short name:
EAR-1
Gene namesi
Name:Nr1d1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi628827. Nr1d1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • Cytoplasm By similarity
  • Cell projectiondendrite By similarity
  • Cell projectiondendritic spine By similarity

  • Note: Localizes to the cytoplasm, dendrites and dendritic spine in the presence of OPHN1.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • dendrite Source: UniProtKB
  • dendritic spine Source: UniProtKB
  • neuronal cell body Source: RGD
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 615615Nuclear receptor subfamily 1 group D member 1PRO_0000053500Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei55 – 551Phosphoserine; by GSK3-betaBy similarity
Modified residuei59 – 591Phosphoserine; by GSK3-betaBy similarity
Modified residuei192 – 1921N6-acetyllysine; by KAT5By similarity
Modified residuei193 – 1931N6-acetyllysine; by KAT5By similarity
Modified residuei401 – 4011N6-acetyllysineBy similarity
Modified residuei592 – 5921N6-acetyllysineBy similarity

Post-translational modificationi

Ubiquitinated, leading to its proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ63503.

PTM databases

iPTMnetiQ63503.

Expressioni

Inductioni

In bladder smooth muscle cells, exhibits night/day variations with a peak time at circadian time (CT) 4-12 and a trough at CT16-24.1 Publication

Interactioni

Subunit structurei

Binds DNA as a monomer or a homodimer. Interacts with C1D, NR2E3, SP1 and ZNHIT1. Interacts with OPHN1 (via C-terminus). Interacts with PER2; the interaction associates PER2 to ARNTL promoter region. Interacts with CRY1. Interacts with CCAR2 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ63503. 1 interaction.
STRINGi10116.ENSRNOP00000012537.

Structurei

3D structure databases

ProteinModelPortaliQ63503.
SMRiQ63503. Positions 128-211, 417-611.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 129129ModulatingAdd
BLAST
Regioni49 – 285237Crucial for activation of GJA1By similarityAdd
BLAST
Regioni207 – 28579HingeAdd
BLAST
Regioni286 – 615330Ligand-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi79 – 9416Poly-SerAdd
BLAST

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri133 – 15321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri170 – 19425NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IMDK. Eukaryota.
ENOG410ZPPI. LUCA.
HOGENOMiHOG000261691.
HOVERGENiHBG106790.
InParanoidiQ63503.
KOiK03728.
PhylomeDBiQ63503.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q63503-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTLDSNNNT GGVITYIGSS GSSPSRTSPE SLYSDSSNGS FQSLTQGCPT
60 70 80 90 100
YFPPSPTGSL TQDPARSFGT VPPSLSDDSS PSSASSSSSS SSSSFYNGSP
110 120 130 140 150
PGSLQVAMED SSRVSPSKGT SNITKLNGMV LLCKVCGDVA SGFHYGVHAC
160 170 180 190 200
EGCKGFFRRS IQQNIQYKRC LKNENCSIVR INRNRCQQCR FKKCLSVGMS
210 220 230 240 250
RDAVRFGRIP KREKQRMLAE MQNAMNLANN QLSSLCPLET SPAPHPTSGS
260 270 280 290 300
VGPSPPPAPA PTPLVGFSQF PQQLTPPRSP SPEPTVEDVI SQVARAHREI
310 320 330 340 350
FTYAHDKLGT SPGNFNANHA SGSPPATTPQ CWESQGCPST PNDNNLLAAQ
360 370 380 390 400
RHNEALNGLR QGPSSYPPTW PSGPAHHSCH QPNSNGHRLC PTHVYSAPEG
410 420 430 440 450
KAPANGLRQG NTKNVLLACP MNMYPHGRSG RTVQEIWEDF SMSFTPAVRE
460 470 480 490 500
VVEFAKHIPG FRDLSQHDQV TLLKAGTFEV LMVRFASLFN VKDQTVMFLS
510 520 530 540 550
RTTYSLQELG AMGMGDLLNA MFDFSEKLNS LALTEEELGL FTAVVLVSAD
560 570 580 590 600
RSGMENSASV EQLQKTLLRA LRALVLKNRP SETSRFTKLL LKLPDLRTLN
610
NMHSEKLLSF RVDAQ
Length:615
Mass (Da):66,693
Last modified:November 13, 2007 - v2
Checksum:i3CC44132F82A25F6
GO

Sequence cautioni

The sequence AAA74939.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti457 – 4571H → Q in AAA74939 (PubMed:2542765).Curated
Sequence conflicti550 – 5512DR → EG in AAA74939 (PubMed:2542765).Curated
Sequence conflicti565 – 5651K → E in AAA74939 (PubMed:2542765).Curated
Sequence conflicti569 – 5691R → G in AAA74939 (PubMed:2542765).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC062047 mRNA. Translation: AAH62047.1.
M25804 mRNA. Translation: AAA74939.1. Different initiation.
PIRiA30226.
RefSeqiNP_001106893.1. NM_001113422.1.
NP_665718.2. NM_145775.2.
UniGeneiRn.29848.

Genome annotation databases

GeneIDi252917.
KEGGirno:252917.
UCSCiRGD:628827. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC062047 mRNA. Translation: AAH62047.1.
M25804 mRNA. Translation: AAA74939.1. Different initiation.
PIRiA30226.
RefSeqiNP_001106893.1. NM_001113422.1.
NP_665718.2. NM_145775.2.
UniGeneiRn.29848.

3D structure databases

ProteinModelPortaliQ63503.
SMRiQ63503. Positions 128-211, 417-611.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63503. 1 interaction.
STRINGi10116.ENSRNOP00000012537.

PTM databases

iPTMnetiQ63503.

Proteomic databases

PaxDbiQ63503.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi252917.
KEGGirno:252917.
UCSCiRGD:628827. rat.

Organism-specific databases

CTDi9572.
RGDi628827. Nr1d1.

Phylogenomic databases

eggNOGiENOG410IMDK. Eukaryota.
ENOG410ZPPI. LUCA.
HOGENOMiHOG000261691.
HOVERGENiHBG106790.
InParanoidiQ63503.
KOiK03728.
PhylomeDBiQ63503.

Miscellaneous databases

PROiQ63503.

Family and domain databases

Gene3Di1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  2. "A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit."
    Lazar M.A., Hodin R.A., Darling D.S., Chin W.W.
    Mol. Cell. Biol. 9:1128-1136(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-615.
  3. "A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbalpha."
    Valnegri P., Khelfaoui M., Dorseuil O., Bassani S., Lagneaux C., Gianfelice A., Benfante R., Chelly J., Billuart P., Sala C., Passafaro M.
    Nat. Neurosci. 14:1293-1301(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH OPHN1.
  4. "Rev-erbalpha regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112."
    Chen H., Chu G., Zhao L., Yamauchi N., Shigeyoshi Y., Hashimoto S., Hattori M.A.
    Biochem. Biophys. Res. Commun. 420:374-379(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Involvement of urinary bladder Connexin43 and the circadian clock in coordination of diurnal micturition rhythm."
    Negoro H., Kanematsu A., Doi M., Suadicani S.O., Matsuo M., Imamura M., Okinami T., Nishikawa N., Oura T., Matsui S., Seo K., Tainaka M., Urabe S., Kiyokage E., Todo T., Okamura H., Tabata Y., Ogawa O.
    Nat. Commun. 3:809-809(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  6. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNR1D1_RAT
AccessioniPrimary (citable) accession number: Q63503
Secondary accession number(s): Q6P6S7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 13, 2007
Last modified: June 8, 2016
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.