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: 87.33   (req: < 5)

Gene RIFs: 20   (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: 87.33   (req: >= 5)

Gene RIFs: 20   (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