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Protein

Nuclear receptor subfamily 1 group D member 2

Gene

Nr1d2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 ARNTL/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.6 Publications

Activity regulationi

The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei381HemeBy similarity1
Binding sitei565HemeBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi100 – 176Nuclear receptorPROSITE-ProRule annotationAdd BLAST77
Zinc fingeri103 – 123NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri140 – 164NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Receptor, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation
LigandHeme, Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 1 group D member 2
Alternative name(s):
Orphan nuclear receptor RVR
Rev-erb-beta
Gene namesi
Name:Nr1d2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:2449205 Nr1d2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535021 – 576Nuclear receptor subfamily 1 group D member 2Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei46Phosphoserine; by GSK3-betaBy similarity1
Modified residuei162N6-acetyllysine; by KAT5By similarity1
Modified residuei163N6-acetyllysine; by KAT5By similarity1
Disulfide bondi334 ↔ 340By similarity
Disulfide bondi371 ↔ 381By similarity

Post-translational modificationi

Deacetylated by HDAC1. Acetylation and deacetylation regulate its transcriptional regulatory activity (By similarity).By similarity
Under more reducing intracellular redox conditions, Cys-381 is in its heme-bound state, which is optimal for recruitment of the NCOR1/HDAC3 corepressor complex and repression of target genes. When subjected to oxidative stress conditions, Cys-381 undergoes oxidation to form a disulfide bridge with Cys-371, also triggering a ligand switch that results in release of bound heme and derepression of target genes (By similarity).By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiQ60674
PRIDEiQ60674

PTM databases

iPTMnetiQ60674
PhosphoSitePlusiQ60674

Expressioni

Tissue specificityi

Ubiquitious. Expressed abundantly in skeletal muscle and brown adipose tissue. Expressed during skeletal muscle myogenesis.2 Publications

Inductioni

Activated by the CLOCK-ARNTL/BMLA1 heterodimer and DBP and repressed by CRY1.1 Publication

Gene expression databases

BgeeiENSMUSG00000021775 Expressed in 306 organ(s), highest expression level in iris
CleanExiMM_NR1D2
ExpressionAtlasiQ60674 baseline and differential
GenevisibleiQ60674 MM

Interactioni

Subunit structurei

Binds DNA as a monomer or a homodimer. Interacts with NCOA5 coactivator, leading to a strong increase of transcription of target genes. Interacts (via N-terminus) with KAT5. Interacts (via C-terminus) with HDAC1. Interacts with ZNHIT1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
NCOA5Q9HCD52EBI-5326205,EBI-2863498From Homo sapiens.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi237266, 1 interactor
IntActiQ60674, 1 interactor
STRINGi10090.ENSMUSP00000088031

Structurei

3D structure databases

ProteinModelPortaliQ60674
SMRiQ60674
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini366 – 576NR LBDPROSITE-ProRule annotationAdd BLAST211

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 99ModulatingAdd BLAST99
Regioni124 – 246HingeAdd BLAST123
Regioni394 – 576Interaction with ZNHIT1By similarityAdd BLAST183

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi13 – 20Poly-Ser8
Compositional biasi35 – 39Poly-Ser5

Domaini

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

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri103 – 123NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri140 – 164NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4846 Eukaryota
ENOG4110581 LUCA
GeneTreeiENSGT00870000136388
HOGENOMiHOG000261691
HOVERGENiHBG106790
InParanoidiQ60674
KOiK08531
OMAiQHLNGQY
OrthoDBiEOG091G066Y
PhylomeDBiQ60674
TreeFamiTF328382

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q60674-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MELNAGGVIA YISSSSSASS PASCHSEGSE NSFQSSSSSV PSSPNSSNCD
60 70 80 90 100
ANGNPKNADI SSIDGVLKSD RTDCPVKTGK TSAPGMTKSH SGMTKFSGMV
110 120 130 140 150
LLCKVCGDVA SGFHYGVHAC EGCKGFFRRS IQQNIQYKKC LKNENCSIMR
160 170 180 190 200
MNRNRCQQCR FKKCLSVGMS RDAVRFGRIP KREKQRMLIE MQSAMKTMMN
210 220 230 240 250
TQFSGHLQND TLAEQHDQSA LPAQEQLRPK SQLEQENIKN TPSDFAKEEV
260 270 280 290 300
IGMVTRAHKD TFLYNQEHRE NSSESMPPQR GERIPRNMEQ YNLNQDHRGS
310 320 330 340 350
GIHNHFPCSE RQQHLSGQYK GRNIMHYPNG HAVCIANGHC MNFSSAYTQR
360 370 380 390 400
VCDRIPVGGC SQTENRNSYL CNTGGRMHLV CPMSKSPYVD PQKSGHEIWE
410 420 430 440 450
EFSMSFTPAV KEVVEFAKRI PGFRDLSQHD QVNLLKAGTF EVLMVRFASL
460 470 480 490 500
FDAKERTVTF LSGKKYSVDD LHSMGAGDLL SSMFEFSEKL NALQLSDEEM
510 520 530 540 550
SLFTAVVLVS ADRSGIENVN SVEALQETLI RALRTLIMKN HPNEASIFTK
560 570
LLLKLPDLRS LNNMHSEELL AFKVHP
Length:576
Mass (Da):64,302
Last modified:November 1, 1996 - v1
Checksum:i6620629052D2CD42
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A286YD98A0A286YD98_MOUSE
Nuclear receptor subfamily 1 group ...
Nr1d2
175Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12142 mRNA Translation: AAA79513.1
U09504 mRNA Translation: AAC52144.1
CCDSiCCDS36811.1
PIRiA57048
RefSeqiNP_035714.3, NM_011584.4
UniGeneiMm.26587

Genome annotation databases

EnsembliENSMUST00000090543; ENSMUSP00000088031; ENSMUSG00000021775
GeneIDi353187
KEGGimmu:353187
UCSCiuc007shp.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12142 mRNA Translation: AAA79513.1
U09504 mRNA Translation: AAC52144.1
CCDSiCCDS36811.1
PIRiA57048
RefSeqiNP_035714.3, NM_011584.4
UniGeneiMm.26587

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EFJmodel-A243-263[»]
B393-576[»]
ProteinModelPortaliQ60674
SMRiQ60674
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi237266, 1 interactor
IntActiQ60674, 1 interactor
STRINGi10090.ENSMUSP00000088031

PTM databases

iPTMnetiQ60674
PhosphoSitePlusiQ60674

Proteomic databases

PaxDbiQ60674
PRIDEiQ60674

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000090543; ENSMUSP00000088031; ENSMUSG00000021775
GeneIDi353187
KEGGimmu:353187
UCSCiuc007shp.2 mouse

Organism-specific databases

CTDi9975
MGIiMGI:2449205 Nr1d2

Phylogenomic databases

eggNOGiKOG4846 Eukaryota
ENOG4110581 LUCA
GeneTreeiENSGT00870000136388
HOGENOMiHOG000261691
HOVERGENiHBG106790
InParanoidiQ60674
KOiK08531
OMAiQHLNGQY
OrthoDBiEOG091G066Y
PhylomeDBiQ60674
TreeFamiTF328382

Enzyme and pathway databases

ReactomeiR-MMU-383280 Nuclear Receptor transcription pathway

Miscellaneous databases

ChiTaRSiNr1d2 mouse
PROiPR:Q60674
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021775 Expressed in 306 organ(s), highest expression level in iris
CleanExiMM_NR1D2
ExpressionAtlasiQ60674 baseline and differential
GenevisibleiQ60674 MM

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNR1D2_MOUSE
AccessioniPrimary (citable) accession number: Q60674
Secondary accession number(s): Q60646
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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