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The RAR-related orphan receptors (RORs) are members of the nuclear receptor family of intracellular transcription factors.[1][2] There are three forms of ROR, ROR-α, -β, and -γ and each is encoded by a separate gene (RORA, RORB, and RORC respectively). The RORs are somewhat unusual in that they appear to bind as monomers to hormone response elements as opposed to the majority of other nuclear receptors which bind as dimers.[3]
Ligands [edit]
Melatonin has been reported to be the endogenous ligand for ROR-α while CGP 52608 has been identified as a ROR-α selective synthetic ligand.[4] However X-ray crystallographic (PDB 1n83 and 1s0x) and functional data both suggest that cholesterol or a cholesterol derivative may be the endogenous ligand.[5]
In contrast, all-trans retinoic acid binds with high affinity to ROR-β and -γ but not ROR-α.[6]
Function [edit]
The three forms of RORs fulfill a number of critical roles[7] including:
References [edit]
- ^ Giguère V, Tini M, Flock G, Ong E, Evans RM, Otulakowski G (1994). "Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors". Genes Dev. 8 (5): 538–53. doi:10.1101/gad.8.5.538. PMID 7926749.
- ^ Hirose T, Smith RJ, Jetten AM (1994). "ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle". Biochem. Biophys. Res. Commun. 205 (3): 1976–83. doi:10.1006/bbrc.1994.2902. PMID 7811290.
- ^ Jetten AM, Kurebayashi S, Ueda E (2001). The ROR nuclear orphan receptor subfamily: Critical regulators of multiple biological processes. "Progress in Nucleic Acid Research and Molecular Biology Volume 69". Prog. Nucleic Acid Res. Mol. Biol. Progress in Nucleic Acid Research and Molecular Biology 69: 205–47. doi:10.1016/S0079-6603(01)69048-2. ISBN 978-0-12-540069-5. PMID 11550795.
- ^ Wiesenberg I, Missbach M, Kahlen JP, Schräder M, Carlberg C (1995). "Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand". Nucleic Acids Res. 23 (3): 327–33. doi:10.1093/nar/23.3.327. PMC 306679. PMID 7885826.
- ^ Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B (December 2002). "X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha". Structure 10 (12): 1697–707. doi:10.1016/S0969-2126(02)00912-7. PMID 12467577.
- ^ Stehlin-Gaon C, Willmann D, Zeyer D, Sanglier S, Van Dorsselaer A, Renaud JP, Moras D, Schüle R (2003). "All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta". Nat. Struct. Biol. 10 (10): 820–5. doi:10.1038/nsb979. PMID 12958591.
- ^ Jetten AM (2004). "Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs)". Current drug targets. Inflammation and allergy 3 (4): 395–412. doi:10.2174/1568010042634497. PMID 15584888.
External links [edit]
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(1) Basic domains
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Activating transcription factor ( AATF, 1, 2, 3, 4, 5, 6, 7) · AP-1 ( c-Fos, FOSB, FOSL1, FOSL2, JDP2, c-Jun, JUNB, JUND) · BACH ( 1, 2) · BATF · BLZF1 · C/EBP ( α, β, γ, δ, ε, ζ) · CREB ( 1, 3, L1) · CREM · DBP · DDIT3 · GABPA · HLF · MAF ( B, F, G, K) · NFE ( 2, L1, L2, L3) · NFIL3 · NRL · NRF ( 1, 2, 3) · XBP1
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(1.2) Basic helix-loop-helix ( bHLH)
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ATOH1 · AhR · AHRR · ARNT · ASCL1 · BHLH ( 2, 9) · BMAL ( ARNTL, ARNTL2) · CLOCK · EPAS1 · FIGLA · HAND ( 1, 2) · HES ( 5, 6) · HEY ( 1, 2, L) · HES1 · HIF ( 1A, 3A) · ID ( 1, 2, 3, 4) · LYL1 · MESP2 · MXD4 · MYCL1 · MYCN · Myogenic regulatory factors ( MyoD, Myogenin, MYF5, MYF6) · Neurogenins ( 1, 2, 3) · NeuroD ( 1, 2) · NPAS ( 1, 2, 3) · OLIG ( 1, 2) · Pho4 · Scleraxis · SIM ( 1, 2) · TAL ( 1, 2) · Twist · USF1
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(1.4) NF-1
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(1.5) RF-X
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(1.6) Basic helix-span-helix (bHSH)
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subfamily 1 ( Thyroid hormone ( α, β), CAR, FXR, LXR ( α, β), PPAR ( α, β/δ, γ), PXR, RAR ( α, β, γ), ROR ( α, β, γ), Rev-ErbA ( α, β), VDR)
subfamily 2 ( COUP-TF ( I, II), Ear-2, HNF4 ( α, γ), PNR, RXR ( α, β, γ), Testicular receptor ( 2, 4), TLX)
subfamily 3 ( Steroid hormone ( Androgen, Estrogen ( α, β), Glucocorticoid, Mineralocorticoid, Progesterone), Estrogen related ( α, β, γ))
subfamily 4 NUR ( NGFIB, NOR1, NURR1) · subfamily 5 ( LRH-1, SF1) · subfamily 6 ( GCNF) · subfamily 0 ( DAX1, SHP)
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(2.2) Other Cys4
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(2.3) Cys2His2
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General transcription factors ( TFIIA, TFIIB, TFIID, TFIIE ( 1, 2), TFIIF ( 1, 2), TFIIH ( 1, 2, 4, 2I, 3A, 3C1, 3C2))
ATBF1 · BCL ( 6, 11A, 11B) · CTCF · E4F1 · EGR ( 1, 2, 3, 4) · ERV3 · GFI1 · GLI-Krüppel family ( 1, 2, 3, REST, S1, S2, YY1) · HIC ( 1, 2) · HIVEP ( 1, 2, 3) · IKZF ( 1, 2, 3) · ILF ( 2, 3) · KLF ( 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17) · MTF1 · MYT1 · OSR1 · PRDM9 · SALL ( 1, 2, 3, 4) · SP ( 1, 2, 4, 7, 8) · TSHZ3 · WT1 · Zbtb7 ( 7A, 7B) · ZBTB ( 11, 16, 17, 20, 32, 33, 40) · zinc finger ( 3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 300, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 644, 649, 655)
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(2.4) Cys6
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(2.5) Alternating composition
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ARX · CDX ( 1, 2) · CRX · CUTL1 · DBX ( 1, 2) · DLX ( 3, 4, 5) · EMX ( 1, 2) · EN ( 1, 2) · FHL ( 1, 2, 3) · HESX1 · HHEX · HLX · Homeobox ( A1, A2, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C12, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) · HOPX · IRX ( 1, 2, 3, 4, 5, 6, MKX) · LMX ( 1A, 1B) · MEIS ( 1, 2) · MEOX2 · MNX1 · MSX ( 1, 2) · NANOG · NKX ( 2-1, 2-2, 2-3, 2-5, 3-1, 3-2, 6-1, 6-2) · NOBOX · PBX ( 1, 2, 3) · PHF ( 1, 3, 6, 8, 10, 16, 17, 20, 21A) · PHOX ( 2A, 2B) · PITX ( 1, 2, 3) · POU domain ( PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11) · OTX ( 1, 2) · PDX1 · SATB2 · SHOX2 · SIX ( 1, 2, 3, 4, 5) · VAX1 · ZEB ( 1, 2)
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(3.2) Paired box
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E2F ( 1, 2, 3, 4, 5) · FOX proteins ( A1, A2, A3, C1, C2, D3, D4, E1, E3, F1, G1, H1, I1, J1, J2, K1, K2, L2, M1, N1, N3, O1, O3, O4, P1, P2, P3, P4)
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(3.5) Tryptophan clusters
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ELF ( 2, 4, 5) · EGF · ELK ( 1, 3, 4) · ERF · ETS ( 1, 2, ERG, SPIB) · ETV ( 1, 4, 5, 6) · FLI1 · Interferon regulatory factors ( 1, 2, 3, 4, 5, 6, 7, 8) · MYB · MYBL2
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(3.6) TEA domain
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transcriptional enhancer factor ( 1, 2, 3, 4)
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(4) β-Scaffold factors with minor groove contacts
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(4.3) p53
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BBX · HMGB ( 1, 2, 3, 4) · HMGN ( 1, 2, 3, 4) · HNF ( 1A, 1B) · LEF1 · SOX ( 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21) · SRY · SSRP1 · TCF ( 3, 4) · TOX ( 1, 2, 3, 4)
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(4.9) Grainyhead
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(4.10) Cold-shock domain
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(4.11) Runt
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(0) Other transcription factors
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(0.2) HMGI(Y)
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(0.6) Miscellaneous
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ARID ( 1A, 1B, 2, 3A, 3B, 4A) · CAP · IFI ( 16, 35) · MLL ( 2, 3, T1) · MNDA · NFY ( A, B, C) · Rho/ Sigma
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see also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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