Receptor Nomenclature NR1B3
Receptor code 4.10.1:RA:1:B3
Molecular information Hs: 454aa, P13631, chr. 12q1313
Rn: chr. 735
Mm: 458aa, P18911, chr. 15 F3,6
DNA binding
   Structure Heterodimer, RXR partner
   HRE core sequence PuG(G/T)TCA (DR2, DR5)
Partners AP-1 (functional): RARγ inhibits AP-1-driven transactivation711; cdk7/TFIIH (physical, functional): TFIIH phosphorylates RARγ 2 in its A/B region (Ser68) by cdk7 subunit12,13; p38 MAPK (functional): required for RA-induced RARγ degradation and transactivation1315; SUG1 (physical, functional): required for RA-induced RARγ degradation and transactivation1315; vinexin β (physical, functional): interacts with AF-1 domain of RARγ and represses RAR-mediated transcription16
Agonists All-trans-retinoic acid (0.2 nM),* 9-cis-retinoic acid (0.8 nM)* [Kd]1721 ; TTNPB (15–26 nM), CD666 (68 nM), BMS270394 (528 nM), BMS961 (500 nM) [IC50]1823
Antagonists AGN193109 (3–7 nM), BMS493 (98 nM), CD2665 (81 nM) [IC50]21,2427
Coactivators NCOA1, NCOA2, NCOA34,2834
Corepressors NCOR1, NCOR229,31,3538
Biologically important isoforms RARγ 1 {Hs, Mm}: differs from RARγ 2 in its N-terminal domain6,39; RARγ 2 {Hs, Mm}: the expression of RARγ 2 is regulated through a specific RARE element; RARγ 2 is phosphorylated by p38 MAPK (Ser66) and by cdk7/TFIIH (Ser68) {Hs, Mm}6,12,14,15,4043
Tissue distribution Highly expressed in the epidermis {Hs, Mm} [Northern blot, in situ hybridization, Western blot]2,6,41,4447
Functional assays Primitive endodermal differentiation and morphological differentiation of the F9 murine embryonal carcinoma cell line {Mm}4850
Main target genes Activated: laminin B1 {Mm}50, RARβ 2 {Hs, Mm, Rn}48,51,52, Hoxa-1 {Mm}4,48,53, CRBP1 {Mm}48,54, CRABPII {Mm}48,55; repressed:
Mutant phenotype Abnormalities observed: growth deficiency, male sterility, squamous epithelia of various epithelia, impaired alveolar formation; congenital defects observed: webbed digits, homeotic transformations and malformations of cervical vertebrae, malformed laryngeal cartilages and tracheal rings, agenesis of the Harderian glands, agenesis of the metopic pillar of the skull, abnormal differentiation of granular keratinocytes; note that specific RARγ 2-null mutants are apparently normal, and specific RARγ 1-null mutants exhibited a growth deficiency, malformations of cervical vertebrae, and abnormal differentiation of granular keratinocytes {Mm} [knockout]5660
Human disease Photoaging: level of RARγ is reduced after UV treatment of human skin6163
  • aa, amino acids; chr., chromosome; HRE, hormone response element; TFIIH, transcription factor IIH; TTNPB, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-pr openyl]benzoic acid

  • * Radioligand

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