Retinoic acid receptor alpha
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Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1) is a
nuclear receptor In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
that in humans is encoded by the ''RARA''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. NR1B1 is a gene with a protein product and has a chromosomal location of 17q21.2. RARA codes for the nuclear hormone receptor Retinoic Acid Receptor, Alpha subtype, and are themselves transcription factors. There are another 2 subtypes of RARs, Beta subtype, and Gamma subtype.


Function

Retinoid signaling is transduced by 2 families of nuclear receptors, retinoic acid receptor ( RAR) and retinoid X receptor ( RXR), which form RXR/RAR heterodimers. In the absence of ligand, DNA-bound RXR/RARA represses transcription by recruiting the corepressors
NCOR1 The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which c ...
, SMRT ( NCOR2), and histone deacetylase. When ligand binds to the complex, it induces a conformational change allowing the recruitment of coactivators, histone acetyltransferases, and the basic transcription machinery. Retinoic Acid Receptor Alpha, the protein, interacts with
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in ...
, a derivative of
Vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...
, which plays an important role in cell growth, differentiation, and the formation of organs in embryonic development. Once Retinoic Acid binds to the RAR, they initiate
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
and allow for their respective gene to be expressed.  


Clinical significance

RA signaling has been correlated with several signaling pathways in early
embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
. First, it participates in the formation of the embryonic axis, which establishes symmetry in the offspring. RA also influences neural differentiation by regulating the expression of pro-neural induction factor Neurogenin 2 (
Neurog2 Neurogenin-2 is a protein that in humans is encoded by the ''NEUROG2'' gene. Neurogenin-2 is a member of the neurogenin subfamily of basic helix-loop-helix ( bHLH) transcription factor In molecular biology, a transcription factor (TF) (or s ...
). RA affects cardiogenesis, as it plays a role specifically in the formation of the atrial chambers of the heart. RA also plays a role in the development of the pancreas, kidneys, lungs, and extremities.  
Translocations In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...
that always involve rearrangement of the RARA gene are a cardinal feature of acute promyelocytic leukemia (APL; MIM 612376). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene.


Interactions

Retinoic acid receptor alpha has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with: *
BAG1 BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the ''BAG1'' gene. Function The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein ...
, *
CLOCK A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and the ...
, * CCND3, *
NCOA6 Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene. Function The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcrip ...
, *
NCOR1 The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which c ...
, * NCOR2, *
NPAS2 Neuronal PAS domain protein 2 (NPAS2) also known as member of PAS protein 4 (MOP4) is a transcription factor protein that in humans is encoded by the ''NPAS2'' gene. NPAS2 is paralogous to CLOCK, and both are key proteins involved in the maintenan ...
, *
NRIP1 Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the ''NRIP1'' gene. Function Nuclear receptor interacting protein 1 (NRIP1) is a nuclear prote ...
, * NR0B2, * NR4A2, * PML *
RXRA Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear receptor that in humans is encoded by the ''RXRA'' gene. Function Retinoid X receptors (RXRs) and retinoic acid receptor ...
. * Src, *
TADA3L Transcriptional adapter 3-like is a protein that in humans is encoded by the ''TADA3'' gene. Cytogenetic location: 3p25.3 Function Many DNA-binding transcriptional activator proteins enhance the initiation rate of RNA polymerase II-mediated ge ...
, and * ZBTB16.


Genetic Studies

Knock-out mice studies showed that a deletion in one of the copies of the RARA gene did not create any observable defect, while deletion of both copies shows symptoms similar to that of Vitamin A deficiency. This proved that all 3 subtypes of RARs work redundantly.


Ligands

;Antagonists * BMS-189453 (non selective) * YCT529 (selective for RAR-α)


See also

*
Retinoic acid receptor The retinoic acid receptor (RAR) is a type of nuclear receptor which can also act as a ligand-activated transcription factor that is activated by both all-trans retinoic acid and 9-cis retinoic acid the retinoid active derivatives of Vitamin A ...
* Retinoic X Receptor * Acute promyelocytic leukemia


References


Further reading

* * * * * * * * * * * * * * * * * {{DEFAULTSORT:Retinoic Acid Receptor Alpha Intracellular receptors Transcription factors