InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RORC

Summary

InnateDB Protein

IDBP-102438.7

Last Modified

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

Gene Symbol

RORC

Protein Name

RAR-related orphan receptor C

Synonyms

NR1F3; RORG; RZR-GAMMA; RZRG; TOR;

Species

Homo sapiens

Ensembl Protein

ENSP00000349164

InnateDB Gene

IDBG-102434 (RORC)

Protein Structure

UniProt Annotation

Function

Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25- hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue- selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC- mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1.Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR- J(alpha) locus.

Subcellular Localization

Nucleus {ECO:0000305}.

Disease Associations

Tissue Specificity

Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. Isoform 2 is primarily expressed in immature thymocytes.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 30 experimentally validated interaction(s) in this database.
They are also associated with 18 interaction(s) predicted by orthology.

Experimentally validated
Total	30 [view]
Protein-Protein	28 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	18 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003707	steroid hormone receptor activity
GO:0004879	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
GO:0005515	protein binding
GO:0008142	oxysterol binding
GO:0008270	zinc ion binding
GO:0043565	sequence-specific DNA binding
GO:0098531	direct ligand regulated sequence-specific DNA binding transcription factor activity

Biological Process

GO:0006355	regulation of transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006805	xenobiotic metabolic process
GO:0010467	gene expression
GO:0010906	regulation of glucose metabolic process
GO:0019218	regulation of steroid metabolic process
GO:0030522	intracellular receptor signaling pathway
GO:0032922	circadian regulation of gene expression
GO:0036315	cellular response to sterol
GO:0042093	T-helper cell differentiation
GO:0042753	positive regulation of circadian rhythm
GO:0043401	steroid hormone mediated signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0045598	regulation of fat cell differentiation
GO:0048535	lymph node development
GO:0048541	Peyer's patch development
GO:0060612	adipose tissue development
GO:0060850	regulation of transcription involved in cell fate commitment
GO:0070244	negative regulation of thymocyte apoptotic process
GO:0072539	T-helper 17 cell differentiation

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000536 Nuclear hormone receptor, ligand-binding, core
IPR001628 Zinc finger, nuclear hormone receptor-type
IPR001723 Steroid hormone receptor
IPR001728 Thyroid hormone receptor
IPR003079 Nuclear receptor ROR
IPR008946 Nuclear hormone receptor, ligand-binding

PFAM

PF00104
PF00105

PRINTS

PR00047
PR00398
PR00546
PR01293

PIRSF

SMART

SM00430
SM00399

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt