Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002529
UniProt IDP51449
Primary gene name(s)RORC
Synonym gene name(s)NR1F3, RORG, RZRG
Protein nameNuclear receptor ROR-gamma
Protein functionNuclear 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, PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100. 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, PubMed:19965867, PubMed:22789990. 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, PubMed:19965867. 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, PubMed:19965867. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization, PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100. Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity, PubMed:26160376. {ECO:0000250|UniProtKB:P51450, ECO:0000269|PubMed:19381306, ECO:0000269|PubMed:19965867, ECO:0000269|PubMed:20203100, ECO:0000269|PubMed:22789990, ECO:0000269|PubMed:26160376}.; FUNCTION: 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(H17 cells, antagonizing the T(H1 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. {ECO:0000269|PubMed:21499262}.
Subcellular locationNucleus {ECO:0000269|PubMed:26160376}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P51449
Gene Ontology
(Biological Process)
Complete annatation
adipose tissue development [GO:0060612];
cellular response to sterol [GO:0036315];
circadian regulation of gene expression [GO:0032922];
lymph node development [GO:0048535];
negative regulation of thymocyte apoptotic process [GO:0070244];
Peyer's patch development [GO:0048541];
positive regulation of circadian rhythm [GO:0042753];
positive regulation of transcription, DNA-templated [GO:0045893];
regulation of fat cell differentiation [GO:0045598];
regulation of glucose metabolic process [GO:0010906];
regulation of steroid metabolic process [GO:0019218];
regulation of transcription involved in cell fate commitment [GO:0060850];
T-helper 17 cell differentiation [GO:0072539];
T-helper cell differentiation [GO:0042093];
transcription initiation from RNA polymerase II promoter [GO:0006367];
xenobiotic metabolic process [GO:0006805]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
oxysterol binding [GO:0008142];
RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding [GO:0004879];
sequence-specific DNA binding [GO:0043565];
steroid hormone receptor activity [GO:0003707];
transcription factor activity, direct ligand regulated sequence-specific DNA binding [GO:0098531];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
intracellular membrane-bounded organelle [GO:0043231];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction112024
Phylogenetic treeP51449
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation-0.6080375978913890.5685268291225820.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
-0.6313 0.01181

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change -1.886351082
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -1.93507 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3B0W X-ray 2.2Å A/B=265-507.
3KYT X-ray 2.3Å A=265-507.
3L0J X-ray 2.4Å A=265-507.
3L0L X-ray 1.7Å A/B=260-507.
4NB6 X-ray 2.8Å A/B=262-507.
4NIE X-ray 2.0Å A/B=263-509.
4QM0 X-ray 2.2Å A/C=262-507.
4S14 X-ray 3.5Å A=262-518.
4WLB X-ray 1.7Å A/B=262-507.
4WPF X-ray 2.2Å A/D=262-509.
4WQP X-ray 1.9Å A/B=262-507# P=480-492.
4XT9 X-ray 2.2Å A=265-507.
4YMQ X-ray 2.0Å A=260-507.
4YPQ X-ray 2.3Å A=265-507.
4ZJR X-ray 2.7Å A/B/C/D=265-487.
4ZJW X-ray 2.5Å A/B=265-487.
4ZOM X-ray 2.2Å A/B/C/D=265-487.
5APH X-ray 1.5Å A=265-507.
5APJ X-ray 2.0Å A=265-507.
5APK X-ray 2.1Å A/B=265-507# D=480-492.
5AYG X-ray 2.6Å A/B=261-518.
5C4O X-ray 2.2Å A=267-507.
5C4S X-ray 2.2Å A=267-507.
5C4T X-ray 1.7Å A=267-507.
5C4U X-ray 2.0Å A=267-507.
5EJV X-ray 2.5Å A/B=259-518.
5ETH X-ray 2.8Å A/B=267-487.
5G42 X-ray 1.7Å A=265-507.
5G43 X-ray 2.5Å A=265-507.
5G44 X-ray 1.8Å A=265-507.
5G45 X-ray 2.0Å A=265-507.
5G46 X-ray 1.7Å A=265-507.
5IXK X-ray 2.3Å A/B=268-487.
5IZ0 X-ray 2.6Å A/B/D/G=259-518.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)