Tchem NR1D2 Nuclear receptor subfamily 1 group D member 2

Protein Summary

Description

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. This gene encodes a member of the nuclear hormone receptor family, specifically the NR1 subfamily of receptors. The encoded protein functions as a transcriptional repressor and may play a role in circadian rhythms and carbohydrate and lipid metabolism. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

Uniprot Accession IDs

• Q14995
• B2R8Q3
• O00402
• Q86XD4

Gene Name

• NR1D2

Ensembl ID

• ENST00000312521
• ENSP00000310006
• ENSG00000174738

Symbol

• RVR
• BD73
• EAR-1R
• REVERBB
• REVERBbeta

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.91
virus perturbation	0.85
disease perturbation	0.79
biological process	0.75
small molecule perturbation	0.75

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Nuclear Receptor Subfamily 1 Group D Member 2

Protein / Receptor / Nuclear Receptor Subfamily 1 Group D Member 2

Protein / Nucleic Acid Binding / Nuclear Receptor Subfamily 1 Group D Member 2

Protein / ... / C4 Zinc Finger Nuclear Receptor / Nuclear Receptor Subfamily 1 Group D Member 2

DTO Classes

Protein / Nuclear Receptor / Rev-erb Receptors / Nuclear Receptor Subfamily 1 Group D Member 2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 74.44   (req: < 5)

Gene RIFs: 14   (req: <= 3)

Antibodies: 299   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 74.44   (req: >= 5)

Gene RIFs: 14   (req: > 3)

Antibodies: 299   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 30

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (4)

Explore Active Ligands

1 – 4 of 4

SR9009

NR1D2Tchem NR

pIC50 : 6.17

SR9011

NR1D2Tchem NR

pIC50 : 6.25

heme

NR1D2Tchem NR

pKd : 6.45

cobalt protoporphyrin IX

NR1D2Tchem NR

pKd : 5.59

Protein-Protein Interactions (45)

Explore Interacting Targets

1 – 10 of 45

• See Interactions on String-DB

USP48

Tbio

Family:  Enzyme

Novelty:  0.10103618

p_int:  0.999335144

p_ni:  0.000595618

p_wrong:  0.000069238

Score:  0.19

Data Source:  BioPlex,STRINGDB

NR1D1

Tchem

Family:  NR

Novelty:  0.00250799

p_int:  0.978675871

p_wrong:  0.021324128

Score:  0.897

Data Source:  BioPlex,STRINGDB

SATB2

Tbio

Family:  TF

Novelty:  0.00405935

p_int:  0.768301332

p_ni:  0.005192884

p_wrong:  0.226505784

Score:  0.237

Data Source:  BioPlex,STRINGDB

ZNF703

Tbio

Novelty:  0.03956045

p_int:  0.751462482

p_ni:  0.24852319

p_wrong:  0.000014327

Score:  0.242

Data Source:  BioPlex,STRINGDB

MED1

Tbio

Family:  Enzyme

Novelty:  0.00852082

Score:  0.905

Data Source:  STRINGDB

DBP

Tbio

Family:  TF

Novelty:  0.02264853

Score:  0.897

Data Source:  STRINGDB

CRY1

Tchem

Novelty:  0.00116593

Score:  0.878

Data Source:  STRINGDB

ARNTL

Tbio

Family:  TF

Novelty:  0.00102829

Score:  0.876

Data Source:  STRINGDB

PER3

Tbio

Novelty:  0.00350199

Score:  0.858

Data Source:  STRINGDB

CLOCK

Tbio

Family:  TF; Epigenetic

Novelty:  0.00159625

Score:  0.83

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (31)

Reactome (4)

WikiPathways (27)

Gene expression (Transcription) (R-HSA-74160)

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1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436
Reactome	Nuclear Receptor transcription pathway	53 targets	R-HSA-383280
Reactome	RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Name	Explore in Pharos	Explore in Source
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436
Nuclear Receptor transcription pathway	53 targets	R-HSA-383280
RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (33)

Functions (13)

Components (3)

Processes (17)

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1 – 10 of 13

GO Term	Evidence	Assigned by
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
nuclear receptor transcription coactivator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
RNA polymerase II regulatory region sequence-specific DNA binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transcription factor binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transcription regulatory region sequence-specific DNA binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
nuclear receptor activity	Traceable Author Statement (TAS)	UniProtKB
distal enhancer DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (7)

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1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
intelligence	EFO_0004337	8	15	8	6.3	89.2
self reported educational attainment	EFO_0004784	4	3	3	5.7	77.1
mathematical ability	EFO_0004875	3	3	3		72
vitamin D measurement	EFO_0004631	1	1	1		69.2
cognitive function measurement	EFO_0008354	3	2	3		68.5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
intelligence	EFO_0004337	8	6.3	89.2
self reported educational attainment	EFO_0004784	3	5.7	77.1
mathematical ability	EFO_0004875	3		72
vitamin D measurement	EFO_0004631	1		69.2
cognitive function measurement	EFO_0008354	3		68.5

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Biological rhythms
Complete proteome
Disulfide bond
DNA-binding
Heme
Iron
Metal-binding

GWAS Trait Find Similar Targets

No Header	No Header
cognitive function measurement
intelligence
mathematical ability
schizophrenia
self reported educational attainment
testosterone measurement
vitamin D measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
immune system phenotype
mortality/aging
reproductive system phenotype
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	nuclear receptor subfamily 1 group D member 2	VGNC:7078	460230
Macaque	nuclear receptor subfamily 1 group D member 2		701624
Mouse	nuclear receptor subfamily 1, group D, member 2	MGI:2449205	353187
Rat	nuclear receptor subfamily 1, group D, member 2	RGD:628828	259241
Dog	nuclear receptor subfamily 1 group D member 2	VGNC:43941	485643

Species	Name	OMA	EggNOG	Inparanoid
Chimp	nuclear receptor subfamily 1 group D member 2
Macaque	nuclear receptor subfamily 1 group D member 2
Mouse	nuclear receptor subfamily 1, group D, member 2
Rat	nuclear receptor subfamily 1, group D, member 2
Dog	nuclear receptor subfamily 1 group D member 2

Publication Statistics

PubMed Score 74.44

PubMed score by year

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PubTator Score 124.36

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Patents

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Related Publications

Text Mined References (33)

GeneRif Annotations (14)

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PMID	Year	Title