Homeobox Genes DataBase

Drosophila/Vertebrates HOX Genes



Retinoic Acid Receptors (RARs)

Retinoic Acid receptors (RARs) are nuclear receptors related to the steroid and thyroid hormone Receptors, a family of proteins that function as ligand-dependent transcription factors. Several loci encoding RAR isoforms have been identified in mammals - RAR-alpha, -beta and gamma - as well as novel nuclear receptors known as RXR (Retinoid X receptor), which are distantly related to RARs and respond to high concentrations of RA. The RARs show spatially restricted distribution patterns during embryogenesis, which have led to speculation on a variety of roles for RA in developmental processes. As with other enhancer-binding proteins, nuclear receptors act as transcription factors by binding to specific DNA recognition sequences generally located upstream of responsive genes. Although RARs can activate gene expression through binding to thyroid hormone response elements, a much more specific and potent RA response element (RARE) has been identified recently within the promoter of the RAR-beta gene. This RARE is essential for RA induction of the RAR-beta gene and, when linked to heterologous promoters, can confer transcriptional activation via all three RARs.

Retinoic Acid (RA)

Retinoic acid (RA) may act as a regulator of differentiation at various stages of vertebrate embryogenesis. In particular, the results of exogeneous RA treatment have implicated RA in antero-posterior patterning both along the body axis and in developing Limb bud. A variety of abnormalities, including Neural tube defects, craniofacial abnormalities, and limb defects, have been reported after treatment of pregnant mammals with RA. The recent discovery that RA interacts with nuclear Receptors related to the steroid and thyroid hormone receptors, a family of proteins that function as ligand-dependent transcription factors, suggests that the morphogenetic functions of RA may result at least in part, from activation of developmentally regulated genes by RA receptor (RAR) complexes. An additional feature of retinoid physiology is the existence of a distinct class of molecules, the cellular retinol- and RA-binding proteins (CRBPs and CRABPs), which may modulate the accessibility of RA to the receptors. Representatives of each binding protein also show spatially restricted patterns of expression in the embryo. The complexity of retinoid action was demonstrated further by the recent finding that specific interactions between RARs and other nuclear proteins, including the thyroid hormone receptors and AP-1 transcription factor, can modulate their transcriptional activity.

Retinoic Acid Response Elements (RARE)

TRE-like sequences containing spacers may mediate response to retinoic acid: -GGTAA....[7bp spacer]...TGACC-


Several retinoids can act on activation/repression of Hox- and related genes. These retinoids include All-trans-retinoic acid; 11-cis-retinoic acid and retinol as metabolite of the retinoic acid.

Regulatory Connections

Upstream Genes







Downstream Genes

Regulatory Connections:

HOX-network Map



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Comments are welcome to Alex Spirov

Structure of the HOX Pro DB