RAR-srodni orfan receptor

RAR-srodni orfan receptor A (alfa)
1n83
Identifikatori
Simbol RORA
Alt. simboli RZRA, ROR1, ROR2, ROR3, NR1F1
Entrez 6095
HUGO 10258
OMIM 600825
PDB 1N83
RefSeq NM_002943
UniProt P35398
Drugi podaci
Lokus Hromozom 15 q21-q22
RAR-srodni orfan receptor B (beta)
1k4w
Identifikatori
Simbol RORB
Alt. simboli RZRB, NR1F2, ROR-BETA
Entrez 6096
HUGO 10259
OMIM 601972
PDB 1NQ7
RefSeq NM_006914
UniProt Q92753
Drugi podaci
Lokus Hromozom 9 q22
RAR-srodni orfan receptor C (gama)
3KYT
Identifikatori
Simbol RORC
Alt. simboli RZRG, RORG, NR1F3, TOR
Entrez 6097
HUGO 10260
OMIM 602943
RefSeq NM_005060
UniProt P51449
Drugi podaci
Lokus Hromozom 1 q21

RAR-srodni orfan receptori' (ROR) su članovi familije nuklearnih receptora intracelularnih transkripcionih faktora.[1][2] Postoje tre forme ROR, ROR-α, -β, i -γ i svaki je kodiran posebnim genom (RORA, RORB, i RORC respektivno). ROR proteini us donekle neuobičajeni u tome da se oni izgleda da se vezuju kao monomeri za elemente hormonskog odgovora što je u kontrastu sa većinom drugih nuklearnih receptora koji se vezuju kao dimeri.[3]

Ligandi

Melatonin se smatra endogenim ligandom receptora ROR-α, dok je CGP 52608 identifikovan kao ROR-α selektivni sintetički ligand.[4] Međutim kristalografski (PDB 1n83 i 1s0x) i funkcionalni podaci sugerišu da je holesterol ili jedan of derivata holesterola mogući endogeni ligand.[5]

U kontrastu s tim, sva-trans retinoinska kiselina[6] se vezuje sa visokim afinitetom za ROR-β i -γ ali ne za ROR-α.[7]

Funkcija

Tri forme ROR receptora ispunjavaju brojne kritične uloge[8] uključujući:

Reference

  1. ↑ 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. 
  2. ↑ 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. 
  3. ↑ Jetten AM, Kurebayashi S, Ueda E (2001). „The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes”. Prog. Nucleic Acid Res. Mol. Biol. 69: 205–47. DOI:10.1016/S0079-6603(01)69048-2. PMID 11550795. 
  4. ↑ 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. PMID 7885826. 
  5. ↑ 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. 
  6. ↑ Donald Voet, Judith G. Voet (2005). Biochemistry (3 izd.). Wiley. str. 1494. ISBN 978-0-471-19350-0. 
  7. ↑ 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. 
  8. ↑ 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. 

Spoljašnje veze

  • MeSH RAR-related+orphan+receptor+A
  • MeSH RAR-related+orphan+receptor+B
  • MeSH RAR-related+orphan+receptor+C
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(1) Osnovni domeni
(1.1) Osnovni leucin rajsferšlus (bZIP)
Aktivirajući transkripcioni faktor (AATF, 1, 2, 3, 4, 5, 6, 7) • AP-1 (c-Fos, FOSB, FOSL1, FOSL2, 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) • NFIL3 • NRL • NRF1 • XBP1
(1.2) Osnovni heliks-petlja-heliks (bHLH)
ATOH1 • AhR • AHRR • ARNT • ASCL1 • BHLHB2 • BMAL (ARNTL, ARNTL2) • CLOCK • EPAS1 • HAND (1, 2) • HES (5, 6) • HEY (1, 2, L) • HES1 • HIF (1A, 3A) • ID (1, 2, 3, 4) • LYL1 • MXD4 • MYCL1 • MYCN • Myogenic regulatorni faktori (MyoD, Myogenin, MYF5, MYF6) • Neurogenini (1, 2, 3) • NeuroD (1, 2) • NPAS (1, 2, 3) • OLIG (1, 2) • Pho4 • Scleraxis • TAL (1, 2) • Twist • USF1
(1.3) bHLH-ZIP
AP-4 • MAX • MITF • MNT • MLX • MXI1 • Myc • SREBP (1, 2)
(1.4) NF-1
NFI (A, B, C, X) • SMAD (R-SMAD (1, 2, 3, 5, 9) - I-SMAD (6, 7) - 4)
(1.5) RF-X
RFX (1, 2, 3, 4, 5, ANK)
(1.6) Osnovni heliks-razmak-heliks (bHSH)
AP-2 (α, β, γ, δ, ε)
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(2) Cink prst DNA-vezujući domeni
(2.1) Nuklearni receptor (Cys4)
podfamilija 1 (Tiroidni hormon (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)
podfamilija 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testikularni receptor (2, 4), TLX)
podfamilija 3 (Steroidni hormon (Androgen, Estrogen (α, β), Glukokortikoid, Mineralokortikoid, Progesteron), Estrogen-vezani (α, β, γ))
podfamilija 4 NUR (NGFIB, NOR1, NURR1) • podfamilija 5 (LRH-1, SF1) • podfamilija 6 (GCNF) • podfamilija 0 (DAX1, SHP)
(2.2) Drugi Cys4
GATA (1, 2, 3, 4, 5, 6) • MTA (1, 2, 3) • TRPS1
(2.3) Cys2His2
Generalni transkripcioni faktori (TFIIA, TFIIB, TFIID, TFIIE, TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2))
ATBF1 • BCL (6, 11A, 11B) • CTCF • E4F1 • EGR (2, 3) • ERV3 • GFI1 • GLI-Kruppel familija (1, 2, 3, REST, 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, 17) • MTF1 • MYT1 • OSR1 • SP (1, 2, 4, 7) • WT1 • Zbtb7 (7A, 7B) • ZBTB (16, 17, 20, 32, 33, 40) • cink prst (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, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 649, 655)
(2.4) Cys6
HIVEP1
(2.5) Naizmenična kompozicija
AIRE • DIDO1 • GRLF1 • ING (1, 2, 4) • JARID (1A, 1B, 1C, 1D, 2) • JMJD1B
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(3.1) Homeodomen
ARX • CDX (1, 2) • CRX • CUTL1 • DBX (1, 2)  • DLX (3, 4, 5) • EMX2 • 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, 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) • PBX (1, 2, 3) • PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) • PITX (1, 2, 3) • POU domen (PIT-1, BRN-3: A, B, C, Oktamer transkripcioni faktor: 1, 2, 3/4, 6, 7, 11) • OTX (1, 2) • PDX1 • ZEB (1, 2)
(3.2) Paired box
PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)
(3.3) Fork glava / winged heliks
E2F (1, 2, 3, 4, 5) • FOX proteini (C1, C2, D3, E1, G1, H1, K2, L2, M1, N3, O1, O3, O4, P1, P2, P3)
(3.4) Faktori toplotnog šoka
HSF (1, 2, 4)
(3.5) Triptofan klasteri
ELF (2, 4, 5) • EGF • ELK (1, 3, 4) • ERF • ERG • ETS (1, 2, SPIB) • ETV (1, 4, 5, 6) • FLI1 • Interferon regulatorni faktori (1, 2, 3, 4, 5, 6, 7, 8) • MYB • MYBL2
(3.6) TEA domen
transkripcioni pojačivač faktor (1, 2, 3, 4)
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(4) β-Scaffold faktori sa manjim žljebnim kontaktima
(4.1) Rel homologni region
NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (C1, C2, C3, C4, 5)
(4.2) STAT
STAT (1, 2, 3, 4, 5, 6)
(4.3) p53
p53 • TBX (1, 2, 3, 5, 19, 21, 22, Brahiuri, TBR1)
(4.4) MADS kutija
Mef2 (A, B, C, D) • SRF
(4.6) TATA vezujući proteini
TBP • TBPL1
(4.7) Grupa visoke pokretljivosti
HMGB (1, 2, 3) • 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)
(4.10) Domen hladnog šoka
CSDA, YBX1
(4.11) Runt
CBF (CBFA2T2, CBFA2T3, RUNX1, RUNX2, RUNX3, RUNX1T1)
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(0) Drugi transkripcioni faktori
(0.2) HMGI(Y)
HMGA (1, 2) • HBP1
(0.3) Džep domen
Rb • RBL1 • RBL2
(0.5) AP-2/EREBP-vezani faktori
Apetala 2 • EREBP • B3
(0.6) Razno
ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma
vidi isto transkripcioni faktor/koregulator nedostataka