Nuclear receptor ROR-gamma

Details

Name
Nuclear receptor ROR-gamma
Kind
protein
Synonyms
  • NR1F3
  • Nuclear receptor RZR-gamma
  • Nuclear receptor subfamily 1 group F member 3
  • RAR-related orphan receptor C
  • Retinoid-related orphan receptor-gamma
  • RORG
  • RZRG
Gene Name
RORC
UniProtKB Entry
P51449Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0009280|Nuclear receptor ROR-gamma
MDRAPQRQHRASRELLAAKKTHTSQIEVIPCKICGDKSSGIHYGVITCEGCKGFFRRSQR
CNAAYSCTRQQNCPIDRTSRNRCQHCRLQKCLALGMSRDAVKFGRMSKKQRDSLHAEVQK
QLQQRQQQQQEPVVKTPPAGAQGADTLTYTLGLPDGQLPLGSSPDLPEASACPPGLLKAS
GSGPSYSNNLAKAGLNGASCHLEYSPERGKAEGRESFYSTGSQLTPDRCGLRFEEHRHPG
LGELGQGPDSYGSPSFRSTPEAPYASLTEIEHLVQSVCKSYRETCQLRLEDLLRQRSNIF
SREEVTGYQRKSMWEMWERCAHHLTEAIQYVVEFAKRLSGFMELCQNDQIVLLKAGAMEV
VLVRMCRAYNADNRTVFFEGKYGGMELFRALGCSELISSIFDFSHSLSALHFSEDEIALY
TALVLINAHRPGLQEKRKVEQLQYNLELAFHHHLCKTHRQSILAKLPPKGKLRSLCSQHV
ERLQIFQHLHPIVVQAAFPPLYKELFSTETESPVGLSK
Number of residues
518
Molecular Weight
58194.845
Theoretical pI
Not Available
GO Classification
Functions
DNA-binding transcription factor activity / DNA-binding transcription factor activity, RNA polymerase II-specific / DNA-binding transcription repressor activity, RNA polymerase II-specific / ligand-activated transcription factor activity / nuclear receptor activity / oxysterol binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / sequence-specific double-stranded DNA binding / zinc ion binding
Processes
adipose tissue development / cellular response to sterol / circadian regulation of gene expression / lymph node development / negative regulation of thymocyte apoptotic process / negative regulation of transcription by RNA polymerase II / Peyer's patch development / positive regulation of circadian rhythm / positive regulation of DNA-templated transcription / regulation of fat cell differentiation / regulation of glucose metabolic process / regulation of steroid metabolic process / regulation of transcription by RNA polymerase II / T-helper 17 cell differentiation / T-helper cell differentiation / xenobiotic metabolic process
Components
chromatin / nuclear body / nucleoplasm / nucleus
General 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 (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). 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, 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 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 a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376)
Specific Function
DNA-binding transcription factor activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
Not Available
Chromosome Location
1
Locus
1q21.3
External Identifiers
ResourceLink
UniProtKB IDP51449
UniProtKB Entry NameRORG_HUMAN
GeneCard IDRORC
HGNC IDHGNC:10260
PDB ID(s)3B0W, 3KYT, 3L0J, 3L0L, 4NB6, 4NIE, 4QM0, 4S14, 4WLB, 4WPF, 4WQP, 4XT9, 4YMQ, 4YPQ, 4ZJR, 4ZJW, 4ZOM, 5APH, 5APJ, 5APK, 5AYG, 5C4O, 5C4S, 5C4T, 5C4U, 5EJV, 5ETH, 5G42, 5G43, 5G44, 5G45, 5G46, 5IXK, 5IZ0, 5K38, 5K3L, 5K3M, 5K3N, 5K6E, 5K74, 5LWP, 5M96, 5NI5, 5NI7, 5NI8, 5NIB, 5NTI, 5NTK, 5NTN, 5NTP, 5NTQ, 5NTW, 5NU1, 5UFO, 5UFR, 5UHI, 5VB3, 5VB5, 5VB6, 5VB7, 5VQK, 5VQL, 5W4R, 5W4V, 5X8Q, 5YP5, 5YP6, 5ZA1, 6A22, 6B30, 6B31, 6B33, 6BN6, 6BR2, 6BR3, 6CN5, 6CN6, 6CVH, 6E3E, 6E3G, 6ESN, 6FGQ, 6FZU, 6G05, 6G07, 6IVX, 6J1L, 6J3N, 6LO9, 6LOA, 6LOB, 6LOC, 6NAD, 6NWS, 6NWT, 6NWU, 6O3Z, 6O98, 6P9F, 6Q2W, 6Q6M, 6Q6O, 6Q7A, 6Q7H, 6R7A, 6R7J, 6R7K, 6SAL, 6SLZ, 6T4G, 6T4I, 6T4J, 6T4K, 6T4T, 6T4U, 6T4W, 6T4X, 6T4Y, 6T50, 6TLM, 6TLQ, 6TLT, 6U25, 6UCG, 6VQF, 6VSW, 6W9H, 6W9I, 6XAE, 6XFV, 7E3M, 7JH2, 7JTM, 7JTW, 7JYM, 7KCO, 7KQJ, 7KXD, 7KXE, 7KXF, 7LUK, 7NEC, 7NP5, 7NP6, 7NPC, 7OFI, 7OFK, 7QP4, 7W3P, 7W3Q, 7XQE, 8FAV, 8FB1, 8FB2, 8GXP, 8XU5
KEGG IDhsa:6097
IUPHAR/Guide To Pharmacology ID600
NCBI Gene ID6097
General References
Not Available

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
25-HydroxycholesterolexperimentalyestargetagonistDetails
GSK-2981278investigationalyestargetagonistDetails