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
Ostali 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
Ostali 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
Ostali 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:

ROR-α - razvoj cerebeluma i limfni čvorova, lipidni metabolizam, imuno odgovor, održavanje kostiju,
ROR-β – precizna uloga je nepoznata, mada je visoko izražen u mozgu i retini,
ROR-γ – razvoj limfnih čvorova i imuni odgovor, opstanak T pomoćnih 17 ćelija.

Reference

^ 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. PMID 7926749. doi:10.1101/gad.8.5.538.
^ 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. PMID 7811290. doi:10.1006/bbrc.1994.2902.
^ 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. PMID 11550795. doi:10.1016/S0079-6603(01)69048-2.
^ 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. PMID 7885826. doi:10.1093/nar/23.3.327.
^ Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B (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. PMID 12467577. doi:10.1016/S0969-2126(02)00912-7.
^ Donald Voet; Judith G. Voet (2005). Biochemistry (3 изд.). Wiley. стр. 1494. ISBN 9780471193500.
^ 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. PMID 12958591. doi:10.1038/nsb979.
^ 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. PMID 15584888. doi:10.2174/1568010042634497.

Literatura

Spoljašnje veze

RAR-related+orphan+receptor+A на US National Library of Medicine Medical Subject Headings (MeSH)
RAR-related+orphan+receptor+B на US National Library of Medicine Medical Subject Headings (MeSH)
RAR-related+orphan+receptor+C на US National Library of Medicine Medical Subject Headings (MeSH)

Transkripcioni faktori i intracelularni receptori

(1) Osnovni domeni

(1.1) Osnovni leucinski zatvarač (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)

(2) DNA-vezujući domeni cinkovog prsta

(2.1) Nuklearni receptor (Cys₄)	potfamilija 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) potfamilija 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testikularni receptor (2, 4), TLX) potfamilija 3 (Steroidni hormon (Androgen, Estrogen (α, β), Glukokortikoid, Mineralokortikoid, Progesteron), Estrogen-vezani (α, β, γ)) potfamilija 4 NUR (NGFIB, NOR1, NURR1) • potfamilija 5 (LRH-1, SF1) • potfamilija 6 (GCNF) • potfamilija 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

(3) Heliks-zavoj-heliks domeni

(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)

(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)

(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
B bsyn: dnk (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)