Receptor Nomenclature NR1B1
Receptor code 4.10.1:RA:1:B1
Molecular information Hs: 462aa, P10276, chr. 17q21.11,2
Rn: 459aa, chr. 101,3
Mm: 462aa, P11416, 11 D1,46
DNA binding
   Structure Heterodimer, RXR partner
   HRE core sequence PuG(G/T)TCA (DR1, DR2, DR5)
Partners Cyclin H/cdk7/TFIIH (physical functional): TFIIH phosphorylates RARα1 in its A/B region (Ser77) by cdk7 subunit79; AP-1 (physical, functional): RAR inhibits AP-1-driven transactivation, and AP-1 represses RAR-mediated transcription1014; CRABPII (physical, functional): can enhance the transactivation by RARα-RXR on DR5 element15; PARP-1 (physical, functional): indispensable to RARα-mediated transcription from the RAR α216
Agonists 9-cis-Retinoic acid (0.3 nM),* all-trans-retinoic acid (0.4 nM),* AGN195183 (3 nM) [Kd]1722; Am580 (36 nM), TTNPB (36–72 nM), Am80 (124 nM) [IC50]1923; BMS75324
Antagonists BMS614 (2 nM), BMS493 (4.2 nM), AGN193109 (2–16 nM), Ro-41-5253 (60 nM) [IC50]19,22,2428
Coactivators NCOA1, NCOA2, NCOA3, PPARBP, CREBBP, p30012,2939
Corepressors NCOR1, NCOR24044
Biologically important isoforms RARα1 {Hm, Mm}: transcribed from the promoter P1 and differs from RARα2 in the A domain—RARα1 is phosphorylated by cdk7/TFIIH (Ser77)5,45,46; RARα2 {Hs, Mm}: in contrast with the RARα1 isoform, RARα2 is transcribed from downstream promoter P2, which contains a DR5 and is inducible by retinoid5,47
Tissue distribution Majority of tissues {Hs, Mm, Rn} [Northern blot, in situ hybridization, Western blot]6,4854
Functional assays Inhibition of cellular proliferation of the MCF-7 breast cancer cell line expressing the estrogen receptor {Hs}55; induction of maturation of acute myeloid leukemia cell lines (NB4, PBL985, U937, HL60) using the histological nitro blue tetrazolium reaction and analysis of CD11c integrin expression by direct immunofluorescence {Hs}21,32,56 ,57; parietal endodermal differentiation in the presence of cAMP of F9 murine embryonal carcinoma cell line {Mm}58
Main target genes Activated: CYP26 {Hs, Mm, Rn},59 RARβ2 {Hs, Mm, Rn}26,57,60,61, Hoxa-1 {Mm}51,60,62 , CRBP1 {Mm}60,63, CRABPII {Mm}60,64
Mutant phenotype Abnormalities observed: growth retardation, male sterility, impaired alveolar formation; congenital defects observed: webbed digits, homeotic transformations and malformations of cervical vertebrae, pterygoquadrate cartilage, malformations of the squamosal bone; note that both the specific RARα1-null and RARα2-null mutants are apparently normal {Mm} [knockout]34,6567
Human disease APL, a subtype of acute myelogenous leukemia: caused by several translocations that implicate the human RARα gene; the reciprocal chromosomal translocation between RARα and PML human genes produces a fusion protein PML-RARα; the use of supraphysiological doses of ATRA lead to remission in patients with APL; in contrast, the fusion protein resulting from the translocation between RARα and the PLZF is insensitive to ATRA treatment6870
  • aa, amino acids; chr., chromosome; HRE, hormone response element; PARP-1, poly(ADP-ribose) polymerase 1; TTNPB, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-pr openyl]benzoic acid; PPARBP, peroxisome proliferator-activated receptor binding protein; CREBBP, cAMP response element-binding protein-binding protein

  • * Radioligand

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