InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Nr1d2

Summary

InnateDB Protein

IDBP-133627.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Nr1d2

Protein Name

nuclear receptor subfamily 1, group D, member 2

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000088031

InnateDB Gene

IDBG-133625 (Nr1d2)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:15623503, ECO:0000269PubMed:18454201, ECO:0000269PubMed:19682428, ECO:0000269PubMed:22474260, ECO:0000269PubMed:23221024, ECO:0000269PubMed:23728303}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00407}.

Disease Associations

Tissue Specificity

Ubiquitious. Expressed abundantly in skeletal muscle and brown adipose tissue. Expressed during skeletal muscle myogenesis. {ECO:0000269PubMed:15623503, ECO:0000269PubMed:18454201}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 12 interaction(s) predicted by orthology.

Experimentally validated
Total	2 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	12 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001046	core promoter sequence-specific DNA binding
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0004887	thyroid hormone receptor activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0043565	sequence-specific DNA binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0019216	regulation of lipid metabolic process
GO:0030522	intracellular receptor signaling pathway
GO:0042752	regulation of circadian rhythm
GO:0043401	steroid hormone mediated signaling pathway
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0048511	rhythmic process
GO:0050727	regulation of inflammatory response
GO:0055088	lipid homeostasis
GO:2000505	regulation of energy homeostasis
GO:2001014	regulation of skeletal muscle cell differentiation

Cellular Component

GO:0005634

nucleus

Protein Structure and Domains

PDB ID

MGI:2449205

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR001728 Thyroid hormone receptor
IPR003078 Retinoic acid receptor
IPR008946 Nuclear hormone receptor, ligand-binding

PFAM

PF00104
PF00105

PRINTS

PR00047
PR00398
PR00546
PR01292

PIRSF

SMART

SM00430
SM00399

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt