What is the Difference Between Retinoic Acid Receptor Alpha Beta and Gamma

The key difference between retinoic acid receptor alpha beta and gamma is that retinoic acid receptor alpha is coded by the gene RARA while retinoic acid receptor beta is coded by the gene RARB, and retinoic acid receptor gamma is coded by the gene RARG.

Retinoic acid receptors are nuclear receptors. They also act as transcriptional factors or activators. There are three sub-types of retinoic acid receptors as retinoic acid receptor alpha, retinoic acid receptor beta and retinoic acid receptor gamma. They bind with all-trans retinoic acid and 9-cis retinoic acid and get activated. Retinoic acid is a signalling molecule and the active form of vitamin A. It is essential for the normal development process of organs in vertebrates (organogenesis). Retinoic acid receptors mediate the effects of retinoic acid by binding with retinoic acid and help in the signalling pathways.

CONTENTS

1. Overview and Key Difference
2. What is Retinoic Acid Receptor Alpha  
3. What is Retinoic Acid Receptor Beta 
4. What is Retinoic Acid Receptor Gamma
4. Similarities – Retinoic Acid Receptor Alpha Beta and Gamma
5. Retinoic Acid Receptor Alpha vs Beta vs Gamma in Tabular Form
6. Summary – Retinoic Acid Receptor Alpha vs Beta vs Gamma

What is Retinoic Acid Receptor Alpha?

Retinoic acid receptor alpha is one of the three subtypes of retinoic acid receptors. It is coded by the gene RARA. There are two isoforms of this receptor protein that differ from their N terminal AF-1 domain. They are RARα1 and RARα2.

RARα is a nuclear receptor residing in the nucleus. It is also a transcriptional factor. RARα participates in regulating myeloid differentiation. Retinoic acid receptors show similar affinity. But their kinetics of the binding is different. RARα displaces 9-cis retinoic acid six-fold more than RARβ. Met 406 and Leu 410 in RARα are very important when binding with 9-cis retinoic acid.

What is Retinoic Acid Receptor Beta?

Retinoic acid receptor beta is another subtype of retinoic acid receptors. This receptor protein is coded by the gene RARB. Generally, RARs are tumor suppressors. Methylation of the RARB gene is found to be correlated with tumor progression.

The methylation status of the RARB gene promoter in human thyroid cancer cell lines is evidence for this. In contrast, demethylation of these genes predominantly inhibits cell growth. Moreover, RARβ is generally poorly expressed in myeloid cells.

What is Retinoic Acid Receptor Gamma?

Retinoic acid receptor gamma is a subtype of retinoic acid receptors. It is also a nuclear hormone receptor. RARγ is coded by the gene RARG. Embryonal Carcinoma and Exfoliative Ichthyosis are two diseases associated with the RARG gene.

The expression of the RARG gene is readily detected in myeloid cells. Moreover, human skin predominantly expresses RARγ in comparison to the other two types. Most importantly, RARγ prefers to bind with all-trans retinoic acid as its ligand than 9-cis retinoic acid.

Similarities Between Retinoic Acid Receptor Alpha Beta and Gamma

• Retinoic acid receptors alpha, beta and gamma are three subtypes identified in vertebrate genome.
• They are nuclear receptors.
• Therefore, they reside mainly in the nucleus.
• They are known as ligand-activated transcription factors.
• They work as transcription factors once they become activated on binding of ligand.
• Moreover, they show similar affinity to bind with the ligand.
• Retinoic acid can activate all three receptor types.
• Once they are activated, they regulate the expression of RA target genes.
• They are able to form functional heterodimers with retinoid X receptors.
• These receptors are also regarded as tumor suppressors.
• They all possess the same architecture of the DNA-binding domain and co-activator binding domain.

Difference Between Retinoic Acid Receptor Alpha Beta and Gamma

Retinoic acid receptor alpha is a subtype of nuclear receptor coded by the gene RARA, while retinoic acid receptor beta is the second subtype of nuclear receptor coded by the gene RARB and retinoic acid receptor gamma is the third subtype of nuclear receptor coded by the gene RARG. So, this is the key difference between the retinoic acid receptor alpha beta and gamma.

The following infographic lists the differences between retinoic acid receptor alpha beta and gamma in tabular form for side by side comparison.

Summary – Retinoic Acid Receptor Alpha vs Beta vs Gamma

Retinoic acid receptors and retinoid X receptors are two families of nuclear receptors that mediate retinoic acid effects and action. Retinoic acid receptors are three types as alpha, beta and gamma.  They are isoforms. These three receptors, α, β, and γ are coded by three distinct nuclear hormone receptor genes. They show a similar architecture but different kinetics in binding with the ligand. Thus, this is the summary of the difference between retinoic acid receptor alpha beta and gamma.

Reference:

1. “Retinoic Acid Receptor.” An Overview | ScienceDirect Topics.
2. JJ, Fisher; GJ, Datta SC; . “Retinoic Acid Receptor-Gamma in Human Epidermis Preferentially Traps All-Trans Retinoic Acid as Its Ligand Rather than 9-Cis Retinoic Acid.” The Journal of Investigative Dermatology, U.S. National Library of Medicine.

Image Courtesy:

1. “Protein RARA PDB 1dkf” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Protein RARB PDB 1dsz” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia
3. “Protein RARG PDB 1dsz” By Emw – Own work (CC BY-SA 3.0) via Commons Wikimedia