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Entry version 184 (13 Feb 2019)
Sequence version 2 (21 Jun 2004)
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Protein

Nuclear receptor ROR-gamma

Gene

RORC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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 (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).By similarity5 Publications
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.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section specifies the position and type of each DNA-binding domain present within the protein.<p><a href='/help/dna_bind' target='_top'>More...</a></p>DNA bindingi31 – 96Nuclear receptorPROSITE-ProRule annotationAdd BLAST66
<p>This subsection of the ‘Function’ section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri31 – 51NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri67 – 91NR C4-typePROSITE-ProRule annotationAdd BLAST25

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Receptor
Biological processBiological rhythms, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P51449

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Nuclear receptor ROR-gamma
Alternative name(s):
Nuclear receptor RZR-gamma
Nuclear receptor subfamily 1 group F member 3
RAR-related orphan receptor C
Retinoid-related orphan receptor-gamma
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:RORC
Synonyms:NR1F3, RORG, RZRG
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000143365.16

Human Gene Nomenclature Database

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HGNCi
HGNC:10260 RORC

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602943 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P51449

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Immunodeficiency 42 (IMD42)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive primary immunodeficiency characterized by increased susceptibility to concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. Mycobacteriosis is characterized by infections caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. IMD42 patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections.
See also OMIM:616622
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07372538S → L in IMD42; does not affect nuclear localization; loss of transcription regulatory region sequence-specific DNA binding; loss of transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs774357869EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi327A → F: Completely abolishes transcriptional activity. 1 Publication1
Mutagenesisi378F → Q: Completely abolishes transcriptional activity. 1 Publication1
Mutagenesisi397I → N: Nearly abolishes transcriptional activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

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DisGeNETi
6097

MalaCards human disease database

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MalaCardsi
RORC
MIMi616622 phenotype

Open Targets

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OpenTargetsi
ENSG00000143365

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
477857 Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA34632

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1741186

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
600

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
RORC

Domain mapping of disease mutations (DMDM)

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DMDMi
49066040

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000535171 – 518Nuclear receptor ROR-gammaAdd BLAST518

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P51449

PeptideAtlas

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PeptideAtlasi
P51449

PRoteomics IDEntifications database

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PRIDEi
P51449

ProteomicsDB human proteome resource

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ProteomicsDBi
56305
56306 [P51449-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P51449

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P51449

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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.

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Up-regulated in the state of obesity.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000143365 Expressed in 101 organ(s), highest expression level in gastrocnemius

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P51449 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P51449 HS

Organism-specific databases

Human Protein Atlas

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HPAi
HPA065620

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts (via AF-2 motif) with the coactivator NCOA2 (via LXXLL motif). Interacts with the corepressor NCOR1. Interacts with CRY1. Interacts (via AF-2 motif) with the coactivators NCOA1 and PPARGC1A (via LXXLL motif) (By similarity). Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with FOXP3.By similarity4 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
112024, 34 interactors

Database of interacting proteins

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DIPi
DIP-60622N

Protein interaction database and analysis system

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IntActi
P51449, 28 interactors

Molecular INTeraction database

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MINTi
P51449

STRING: functional protein association networks

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STRINGi
9606.ENSP00000327025

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P51449

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1518
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B0WX-ray2.20A/B265-507[»]
3KYTX-ray2.35A265-507[»]
3L0JX-ray2.40A265-507[»]
3L0LX-ray1.74A/B260-507[»]
4NB6X-ray2.85A/B262-507[»]
4NIEX-ray2.01A/B263-509[»]
4QM0X-ray2.20A/C262-507[»]
4S14X-ray3.54A262-518[»]
4WLBX-ray1.70A/B262-507[»]
4WPFX-ray2.20A/D262-509[»]
4WQPX-ray1.99A/B262-507[»]
P480-492[»]
4XT9X-ray2.25A265-507[»]
4YMQX-ray2.00A260-507[»]
4YPQX-ray2.32A265-507[»]
4ZJRX-ray2.70A/B/C/D265-487[»]
4ZJWX-ray2.50A/B265-487[»]
4ZOMX-ray2.27A/B/C/D265-487[»]
5APHX-ray1.54A265-507[»]
5APJX-ray2.08A265-507[»]
5APKX-ray2.10A/B265-507[»]
D480-492[»]
5AYGX-ray2.60A/B261-518[»]
5C4OX-ray2.24A267-507[»]
5C4SX-ray2.23A267-507[»]
5C4TX-ray1.77A267-507[»]
5C4UX-ray2.08A267-507[»]
5EJVX-ray2.58A/B259-518[»]
5ETHX-ray2.80A/B267-487[»]
5G42X-ray1.72A265-507[»]
5G43X-ray2.58A265-507[»]
5G44X-ray1.84A265-507[»]
5G45X-ray2.07A265-507[»]
5G46X-ray1.76A265-507[»]
5IXKX-ray2.35A/B268-487[»]
5IZ0X-ray2.63A/B/D/G259-518[»]
5K38X-ray2.05A/B265-507[»]
5K3LX-ray2.75A/B/C/D265-507[»]
5K3MX-ray2.89A/B265-507[»]
5K3NX-ray2.67A/B/C/D265-507[»]
5K6EX-ray2.80A/B265-507[»]
5K74X-ray2.75A/B265-507[»]
5LWPX-ray2.40A265-506[»]
5M96X-ray1.77A/B263-491[»]
5NI5X-ray2.30A265-507[»]
5NI7X-ray2.45A265-507[»]
5NI8X-ray1.94A265-507[»]
5NIBX-ray1.82A265-507[»]
5NTIX-ray2.40A/B/C/D263-518[»]
5NTKX-ray1.90A/B263-491[»]
5NTNX-ray1.90A/B/C/D263-518[»]
5NTPX-ray1.70A263-499[»]
5NTQX-ray2.26A/B263-499[»]
5NTWX-ray1.64A/B/C/D263-518[»]
5NU1X-ray1.85A/B263-518[»]
5UFOX-ray2.80A265-507[»]
5UFRX-ray2.07A/B265-507[»]
5UHIX-ray3.20A/B265-507[»]
5VB3X-ray1.95A260-507[»]
5VB5X-ray2.23A260-507[»]
5VB6X-ray2.04A260-507[»]
5VB7X-ray2.33A260-507[»]
5VQKX-ray3.10A260-507[»]
5VQLX-ray2.70A260-507[»]
5W4RX-ray3.00A/B265-481[»]
5W4VX-ray2.65A/B/C/D/E/F266-475[»]
5X8QX-ray2.20A/C/E/G261-518[»]
5YP5X-ray2.65A265-507[»]
5YP6X-ray2.20A265-507[»]
5ZA1X-ray2.52A/B265-494[»]
6A22X-ray2.55A/C/E/G261-518[»]
6B30X-ray2.69A/B265-479[»]
6B31X-ray3.18A/B265-492[»]
6B33X-ray2.48A/B265-482[»]
6BN6X-ray2.40A/B265-508[»]
6BR2X-ray3.18A/B265-479[»]
6BR3X-ray3.00A/B265-480[»]
6CN5X-ray2.30A/B259-518[»]
6CN6X-ray2.45A259-517[»]
6CVHX-ray3.50A265-489[»]
6ESNX-ray1.84A265-507[»]
6FGQX-ray2.37A/B265-507[»]
6FZUX-ray1.80A/B263-518[»]
6G05X-ray1.90A/B263-518[»]
6G07X-ray1.66A/B/C/D263-518[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P51449

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P51449

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P51449

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini269 – 508NR LBDPROSITE-ProRule annotationAdd BLAST240

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 30ModulatingSequence analysisAdd BLAST30

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi501 – 506AF-26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi121 – 130Poly-Gln10

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri31 – 51NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri67 – 91NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4216 Eukaryota
ENOG410XUGR LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000161521

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG106848

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P51449

KEGG Orthology (KO)

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KOi
K08534

Identification of Orthologs from Complete Genome Data

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OMAi
MDRAPQR

Database of Orthologous Groups

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OrthoDBi
583704at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P51449

TreeFam database of animal gene trees

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TreeFami
TF319910

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.30.50.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR003079 ROR_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA

Pfam protein domain database

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Pfami
View protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR01293 RORNUCRECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48508 SSF48508, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative promoter usage. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P51449-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDRAPQRQHR ASRELLAAKK THTSQIEVIP CKICGDKSSG IHYGVITCEG
60 70 80 90 100
CKGFFRRSQR CNAAYSCTRQ QNCPIDRTSR NRCQHCRLQK CLALGMSRDA
110 120 130 140 150
VKFGRMSKKQ RDSLHAEVQK QLQQRQQQQQ EPVVKTPPAG AQGADTLTYT
160 170 180 190 200
LGLPDGQLPL GSSPDLPEAS ACPPGLLKAS GSGPSYSNNL AKAGLNGASC
210 220 230 240 250
HLEYSPERGK AEGRESFYST GSQLTPDRCG LRFEEHRHPG LGELGQGPDS
260 270 280 290 300
YGSPSFRSTP EAPYASLTEI EHLVQSVCKS YRETCQLRLE DLLRQRSNIF
310 320 330 340 350
SREEVTGYQR KSMWEMWERC AHHLTEAIQY VVEFAKRLSG FMELCQNDQI
360 370 380 390 400
VLLKAGAMEV VLVRMCRAYN ADNRTVFFEG KYGGMELFRA LGCSELISSI
410 420 430 440 450
FDFSHSLSAL HFSEDEIALY TALVLINAHR PGLQEKRKVE QLQYNLELAF
460 470 480 490 500
HHHLCKTHRQ SILAKLPPKG KLRSLCSQHV ERLQIFQHLH PIVVQAAFPP
510
LYKELFSTET ESPVGLSK
Length:518
Mass (Da):58,195
Last modified:June 21, 2004 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i7F423140BD7922BE
GO
Isoform 2 (identifier: P51449-2) [UniParc]FASTAAdd to basket
Also known as: RORgT

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.
     22-24: HTS → MRT

Show »
Length:497
Mass (Da):55,813
Checksum:i6D0048673483EA11
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1W2PRM4A0A1W2PRM4_HUMAN
Nuclear receptor ROR-gamma
RORC
51Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAA64751 differs from that shown. Reason: Frameshift at position 516.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07372538S → L in IMD42; does not affect nuclear localization; loss of transcription regulatory region sequence-specific DNA binding; loss of transcriptional activity. 1 PublicationCorresponds to variant dbSNP:rs774357869EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0106321 – 21Missing in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_01063322 – 24HTS → MRT in isoform 2. 1 Publication3

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U16997 mRNA Translation: AAA64751.1 Frameshift.
AL834219 mRNA Translation: CAD38900.1
AL589765 Genomic DNA No translation available.
BC031554 mRNA Translation: AAH31554.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS1004.1 [P51449-1]
CCDS30856.1 [P51449-2]

Protein sequence database of the Protein Information Resource

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PIRi
JC2494

NCBI Reference Sequences

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RefSeqi
NP_001001523.1, NM_001001523.1 [P51449-2]
NP_005051.2, NM_005060.3 [P51449-1]

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.256022
Hs.607993

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000318247; ENSP00000327025; ENSG00000143365 [P51449-1]
ENST00000356728; ENSP00000349164; ENSG00000143365 [P51449-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
6097

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:6097

UCSC genome browser

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UCSCi
uc001ezg.4 human [P51449-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16997 mRNA Translation: AAA64751.1 Frameshift.
AL834219 mRNA Translation: CAD38900.1
AL589765 Genomic DNA No translation available.
BC031554 mRNA Translation: AAH31554.1
CCDSiCCDS1004.1 [P51449-1]
CCDS30856.1 [P51449-2]
PIRiJC2494
RefSeqiNP_001001523.1, NM_001001523.1 [P51449-2]
NP_005051.2, NM_005060.3 [P51449-1]
UniGeneiHs.256022
Hs.607993

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3B0WX-ray2.20A/B265-507[»]
3KYTX-ray2.35A265-507[»]
3L0JX-ray2.40A265-507[»]
3L0LX-ray1.74A/B260-507[»]
4NB6X-ray2.85A/B262-507[»]
4NIEX-ray2.01A/B263-509[»]
4QM0X-ray2.20A/C262-507[»]
4S14X-ray3.54A262-518[»]
4WLBX-ray1.70A/B262-507[»]
4WPFX-ray2.20A/D262-509[»]
4WQPX-ray1.99A/B262-507[»]
P480-492[»]
4XT9X-ray2.25A265-507[»]
4YMQX-ray2.00A260-507[»]
4YPQX-ray2.32A265-507[»]
4ZJRX-ray2.70A/B/C/D265-487[»]
4ZJWX-ray2.50A/B265-487[»]
4ZOMX-ray2.27A/B/C/D265-487[»]
5APHX-ray1.54A265-507[»]
5APJX-ray2.08A265-507[»]
5APKX-ray2.10A/B265-507[»]
D480-492[»]
5AYGX-ray2.60A/B261-518[»]
5C4OX-ray2.24A267-507[»]
5C4SX-ray2.23A267-507[»]
5C4TX-ray1.77A267-507[»]
5C4UX-ray2.08A267-507[»]
5EJVX-ray2.58A/B259-518[»]
5ETHX-ray2.80A/B267-487[»]
5G42X-ray1.72A265-507[»]
5G43X-ray2.58A265-507[»]
5G44X-ray1.84A265-507[»]
5G45X-ray2.07A265-507[»]
5G46X-ray1.76A265-507[»]
5IXKX-ray2.35A/B268-487[»]
5IZ0X-ray2.63A/B/D/G259-518[»]
5K38X-ray2.05A/B265-507[»]
5K3LX-ray2.75A/B/C/D265-507[»]
5K3MX-ray2.89A/B265-507[»]
5K3NX-ray2.67A/B/C/D265-507[»]
5K6EX-ray2.80A/B265-507[»]
5K74X-ray2.75A/B265-507[»]
5LWPX-ray2.40A265-506[»]
5M96X-ray1.77A/B263-491[»]
5NI5X-ray2.30A265-507[»]
5NI7X-ray2.45A265-507[»]
5NI8X-ray1.94A265-507[»]
5NIBX-ray1.82A265-507[»]
5NTIX-ray2.40A/B/C/D263-518[»]
5NTKX-ray1.90A/B263-491[»]
5NTNX-ray1.90A/B/C/D263-518[»]
5NTPX-ray1.70A263-499[»]
5NTQX-ray2.26A/B263-499[»]
5NTWX-ray1.64A/B/C/D263-518[»]
5NU1X-ray1.85A/B263-518[»]
5UFOX-ray2.80A265-507[»]
5UFRX-ray2.07A/B265-507[»]
5UHIX-ray3.20A/B265-507[»]
5VB3X-ray1.95A260-507[»]
5VB5X-ray2.23A260-507[»]
5VB6X-ray2.04A260-507[»]
5VB7X-ray2.33A260-507[»]
5VQKX-ray3.10A260-507[»]
5VQLX-ray2.70A260-507[»]
5W4RX-ray3.00A/B265-481[»]
5W4VX-ray2.65A/B/C/D/E/F266-475[»]
5X8QX-ray2.20A/C/E/G261-518[»]
5YP5X-ray2.65A265-507[»]
5YP6X-ray2.20A265-507[»]
5ZA1X-ray2.52A/B265-494[»]
6A22X-ray2.55A/C/E/G261-518[»]
6B30X-ray2.69A/B265-479[»]
6B31X-ray3.18A/B265-492[»]
6B33X-ray2.48A/B265-482[»]
6BN6X-ray2.40A/B265-508[»]
6BR2X-ray3.18A/B265-479[»]
6BR3X-ray3.00A/B265-480[»]
6CN5X-ray2.30A/B259-518[»]
6CN6X-ray2.45A259-517[»]
6CVHX-ray3.50A265-489[»]
6ESNX-ray1.84A265-507[»]
6FGQX-ray2.37A/B265-507[»]
6FZUX-ray1.80A/B263-518[»]
6G05X-ray1.90A/B263-518[»]
6G07X-ray1.66A/B/C/D263-518[»]
ProteinModelPortaliP51449
SMRiP51449
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112024, 34 interactors
DIPiDIP-60622N
IntActiP51449, 28 interactors
MINTiP51449
STRINGi9606.ENSP00000327025

Chemistry databases

BindingDBiP51449
ChEMBLiCHEMBL1741186
GuidetoPHARMACOLOGYi600

PTM databases

iPTMnetiP51449
PhosphoSitePlusiP51449

Polymorphism and mutation databases

BioMutaiRORC
DMDMi49066040

Proteomic databases

PaxDbiP51449
PeptideAtlasiP51449
PRIDEiP51449
ProteomicsDBi56305
56306 [P51449-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
6097
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318247; ENSP00000327025; ENSG00000143365 [P51449-1]
ENST00000356728; ENSP00000349164; ENSG00000143365 [P51449-2]
GeneIDi6097
KEGGihsa:6097
UCSCiuc001ezg.4 human [P51449-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
6097
DisGeNETi6097
EuPathDBiHostDB:ENSG00000143365.16

GeneCards: human genes, protein and diseases

More...
GeneCardsi
RORC
HGNCiHGNC:10260 RORC
HPAiHPA065620
MalaCardsiRORC
MIMi602943 gene
616622 phenotype
neXtProtiNX_P51449
OpenTargetsiENSG00000143365
Orphaneti477857 Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
PharmGKBiPA34632

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4216 Eukaryota
ENOG410XUGR LUCA
GeneTreeiENSGT00940000161521
HOVERGENiHBG106848
InParanoidiP51449
KOiK08534
OMAiMDRAPQR
OrthoDBi583704at2759
PhylomeDBiP51449
TreeFamiTF319910

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-8949275 RUNX3 Regulates Immune Response and Cell Migration
SIGNORiP51449

Miscellaneous databases

EvolutionaryTraceiP51449

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
RAR-related_orphan_receptor_gamma

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
6097

Protein Ontology

More...
PROi
PR:P51449

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000143365 Expressed in 101 organ(s), highest expression level in gastrocnemius
ExpressionAtlasiP51449 baseline and differential
GenevisibleiP51449 HS

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR003079 ROR_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01293 RORNUCRECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiRORG_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P51449
Secondary accession number(s): Q5SZR9, Q8N5V7, Q8NCY8
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: June 21, 2004
Last modified: February 13, 2019
This is version 184 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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