Details of Protein

General Information of Protein (ID: PRT00030)
Name Nuclear receptor ROR-gamma (RORC)
Synonyms   Click to Show/Hide Synonyms of This Protein
Nuclear receptor RZR-gamma; Nuclear receptor subfamily 1 group F member 3; RAR-related orphan receptor C; Retinoid-related orphan receptor-gamma; RORC; NR1F3; RORG; RZRG
Gene Name RORC Gene ID
6097
UniProt ID
P51449
Family Nuclear hormone receptor (NHR)
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MDRAPQRQHRASRELLAAKKTHTSQIEVIPCKICGDKSSGIHYGVITCEGCKGFFRRSQR
CNAAYSCTRQQNCPIDRTSRNRCQHCRLQKCLALGMSRDAVKFGRMSKKQRDSLHAEVQK
QLQQRQQQQQEPVVKTPPAGAQGADTLTYTLGLPDGQLPLGSSPDLPEASACPPGLLKAS
GSGPSYSNNLAKAGLNGASCHLEYSPERGKAEGRESFYSTGSQLTPDRCGLRFEEHRHPG
LGELGQGPDSYGSPSFRSTPEAPYASLTEIEHLVQSVCKSYRETCQLRLEDLLRQRSNIF
SREEVTGYQRKSMWEMWERCAHHLTEAIQYVVEFAKRLSGFMELCQNDQIVLLKAGAMEV
VLVRMCRAYNADNRTVFFEGKYGGMELFRALGCSELISSIFDFSHSLSALHFSEDEIALY
TALVLINAHRPGLQEKRKVEQLQYNLELAFHHHLCKTHRQSILAKLPPKGKLRSLCSQHV
ERLQIFQHLHPIVVQAAFPPLYKELFSTETESPVGLSK
Structure
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 ; 7JH2 ; 7JTM ; 7JYM
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 G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization. Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity.; [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.
Regulatory Network
Full List of Metabolite(s) Regulating This Protein
      Lipids and lipid-like molecules
            20-Hydroxycholesterol Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 20-Hydroxycholesterol addition (24h)
                      Induced Change RORC protein binding activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 20-hydroxycholesterol addition causes the increase of RORC protein binding activity compared with control group.
            22-Alpha-Hydroxycholesterol Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 22-Alpha-Hydroxycholesterol addition (24h)
                      Induced Change RORC protein binding activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 22-alpha-Hydroxycholesterol addition causes the increase of RORC protein binding activity compared with control group.
            25-Hydroxycholesterol Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation 25-Hydroxycholesterol addition (24h)
                      Induced Change RORC protein binding activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that 25-hydroxycholesterol addition causes the increase of RORC protein binding activity compared with control group.
            Cholesterol Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Cholesterol addition (24h)
                      Induced Change RORC protein binding activity levels: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that cholesterol addition causes the increase of RORC protein binding activity compared with control group.
References
1 Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. Mol Endocrinol. 2010 May;24(5):923-9.

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