General Information of the Protein
Protein ID
PT05439
Protein Name
Nuclear receptor ROR-gamma
Secondarily
Protein Name
Nuclear receptor RZR-gamma
Nuclear receptor subfamily 1 group F member 3
RAR-related orphan receptor C
Retinoid-related orphan receptor-gamma
Thymus orphan receptor
Gene Name
RORC
Secondarily
Gene Name
Nr1f3
Rorg
Thor
Sequence
MDRAPQRHHRTSRELLAAKKTHTSQIEVIPCKICGDKSSGIHYGVITCEGCKGFFRRSQQCNVAYSCTRQQNCPIDRTSRNRCQHCRLQKCLALGMSRDAVKFGRMSKKQRDSLHAEVQKQLQQQQQQEQVAKTPPAGSRGADTLTYTLGLSDGQLPLGASPDLPEASACPPGLLRASGSGPPYSNTLAKTEVQGASCHLEYSPERGKAEGRDSIYSTDGQLTLGRCGLRFEETRHPELGEPEQGPDSHCIPSFCSAPEVPYASLTDIEYLVQNVCKSFRETCQLRLEDLLRQRTNLFSREEVTSYQRKSMWEMWERCAHHLTEAIQYVVEFAKRLSGFMELCQNDQIILLTAGAMEVVLVRMCRAYNANNHTVFFEGKYGGVELFRALGCSELISSIFDFSHFLSALCFSEDEIALYTALVLINANRPGLQEKRRVEHLQYNLELAFHHHLCKTHRQGLLAKLPPKGKLRSLCSQHVEKLQIFQHLHPIVVQAAFPPLYKELFSTDVESPEGLSK
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Organism
Mus musculus, Mouse
Protein Classification
Transcription factor
>
Nuclear receptor
>
Nuclear hormone receptor subfamily 1
>
Nuclear hormone receptor subfamily 1 group F
>
Nuclear hormone receptor subfamily 1 group F member 3
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 (PubMed:17666523, PubMed:19381306, PubMed:19965867, PubMed:21853531, PubMed:22789990, PubMed:23723244). Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner (PubMed:22753030). Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as 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 (PubMed:22753030). 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 (PubMed:21853531). Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization.
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Uniprot ID
Primary ID:
P51450

Secondarily ID:
E9Q8I1
Q3U513
Q61027
Q91YT5
Q9QXD9
Q9R177
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Subcellular Location
Nucleus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000764 , Bone marrow macrophage immortalized C57BL/6
Compound ID Compound Name Compound Formula
CP0060047
N-[4-(5-acetamido-2-propan-2-ylpyrazol-3-yl)-2-piperidin-1-ylphenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
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C27H31ClFN5O2
 1
1
EC50 = 11 nM
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CP0281549
N-[4-(5-acetamido-2-propan-2-ylpyrazol-3-yl)-2-pyrrolidin-1-ylphenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
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C26H29ClFN5O2
 1
1
EC50 = 17 nM
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CP0717530
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(1-isopropyl-3-propionamido-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C28H31ClFN5O2
 1
1
EC50 = 33 nM
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CP0072489
N-[5-(5-acetamido-2-propan-2-ylpyrazol-3-yl)-3-piperidin-1-ylpyridin-2-yl]-2-chloro-6-fluoro-N-methylbenzamide
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C26H30ClFN6O2
 1
1
EC50 = 34 nM
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CP0674649
N-(4-(3-acetamido-1-isopropyl-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2-chloro-6-fluoro-N-[2H]-methylbenzamide
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C27H29ClFN5O2
 1
1
EC50 = 38 nM
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CP0731677
N-(4-(3-acetamido-1-cyclopentyl-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C29H31ClFN5O2
 1
1
EC50 = 60 nM
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CP0770850
N-(4-(3-acetamido-1-isopropyl-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2,6-dichloro-N-[2H]-methylbenzamide
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C27H29Cl2N5O2
 1
1
EC50 = 73 nM
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CP0694116
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(3-(cyclopropanecarboxamido)-1-isopropyl-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C29H31ClFN5O2
 1
1
EC50 = 88 nM
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CP0199396
N-[4-(5-acetamido-2-propan-2-ylpyrazol-3-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl]-2-chloro-6-fluoro-N-methylbenzamide
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C27H29ClFN5O2
 1
1
EC50 = 110 nM
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CP0806353
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(3-(2-hydroxyacetamido)-1-isopropyl-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N-[2H]-methylbenzamide
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C27H29ClFN5O3
 1
1
EC50 = 120 nM
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CP0849524
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(3-isobutyramido-1-isopropyl-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C29H33ClFN5O2
 1
1
EC50 = 128 nM
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CP0382327
N-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[5-[(3-hydroxycyclobutanecarbonyl)amino]-2-propan-2-ylpyrazol-3-yl]phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
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C30H33ClFN5O3
 1
1
EC50 = 134 nM
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CP0830825
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(3-((1r,3r)-3-hydroxycyclobutanecarboxamido)-1-isopropyl-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C30H33ClFN5O3
 1
1
EC50 = 134 nM
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CP0731675
N-(5-(3-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(2-chloro-6-fluoro-N[2H]-methylbenzamido)phenyl)-1-isopropyl-1H-pyrazol-3-yl)-2-oxa-6-azaspiro[3.3]heptane-6-carboxamide
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C31H34ClFN6O3
 1
1
EC50 = 148 nM
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CP0659888
N-(4-(3-acetamido-1-cyclobutyl-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C28H29ClFN5O2
 1
1
EC50 = 199 nM
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CP0674427
N-(4-(3-acetamido-1-(cyclopropylmethyl)-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C28H29ClFN5O2
 1
1
EC50 = 201 nM
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CP0770851
N-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(1-isopropyl-3-(3-methylureido)-1H-pyrazol-5-yl)phenyl)-2-chloro-6-fluoro-N[2H]-methylbenzamide
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C27H30ClFN6O2
 1
1
EC50 = 354 nM
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CP0660102
N-(4-(3-acetamido-1-isopropyl-1H-pyrazol-5-yl)-2-(3-azabicyclo[3.1.0]hexan-3-yl)phenyl)-2-fluoro-N[2H],6-dimethylbenzamide
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C28H32FN5O2
 1
1
EC50 = 355 nM
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CP0146700
2-chloro-6-fluoro-N-[4-(1-methyl-5-propan-2-ylpyrazol-4-yl)-2-(2,2,2-trifluoroethoxy)phenyl]-N-(trideuteriomethyl)benzamide
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C23H22ClF4N3O2
 1
1
EC50 = 818 nM
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CP0045935
N-[4-(5-carbamoyl-2-chlorophenyl)-2-(2,2,2-trifluoroethoxy)phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
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C23H16Cl2F4N2O3
 1
1
EC50 = 895 nM
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CP0199394
5-[4-[(2-chloro-6-fluorobenzoyl)-(trideuteriomethyl)amino]-3-(2,2,2-trifluoroethoxy)phenyl]-1-propan-2-ylpyrazole-3-carboxamide
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C23H21ClF4N4O3
 1
1
EC50 = 2000 nM
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CP0059556
N-[4-(5-acetamido-2-propan-2-ylpyrazol-3-yl)-2-(cyclobutylmethoxy)phenyl]-2-chloro-6-fluoro-N-(trideuteriomethyl)benzamide
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C27H30ClFN4O3
 1
1
EC50 = 3110 nM
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