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Retinoic acid receptor alpha

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(Redirected from RARA (gene)) Protein found in humans
RARA
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1DKF, 1DSZ, 3A9E, 3KMR, 3KMZ, 4DQM, 5K13

Identifiers
AliasesRARA, NR1B1, RAR, retinoic acid receptor alpha, RARalpha
External IDsOMIM: 180240; MGI: 97856; HomoloGene: 20262; GeneCards: RARA; OMA:RARA - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)
Chromosome 17 (human)Genomic location for RARAGenomic location for RARA
Band17q21.2Start40,309,180 bp
End40,357,643 bp
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)
Chromosome 11 (mouse)Genomic location for RARAGenomic location for RARA
Band11 D|11 62.76 cMStart98,818,644 bp
End98,865,768 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • lactiferous duct

  • monocyte

  • granulocyte

  • blood

  • gallbladder

  • right lung

  • left uterine tube

  • upper lobe of left lung

  • tibial arteries

  • canal of the cervix
Top expressed in
  • granulocyte

  • genital tubercle

  • tail of embryo

  • lip

  • yolk sac

  • spermatocyte

  • neural layer of retina

  • spermatid

  • molar

  • female urethra
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5914

19401

Ensembl

ENSG00000131759

ENSMUSG00000037992

UniProt

P10276
Q6I9R7

P11416

RefSeq (mRNA)

NM_000964
NM_001024809
NM_001033603
NM_001145301
NM_001145302

NM_001176528
NM_001177302
NM_001177303
NM_009024
NM_001361954

RefSeq (protein)
NP_000955
NP_001019980
NP_001138773
NP_001138774
NP_000955.1

NP_001138773.1

NP_001169999
NP_001170773
NP_001170774
NP_033050
NP_001348883

Location (UCSC)Chr 17: 40.31 – 40.36 MbChr 11: 98.82 – 98.87 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Retinoic acid receptor alpha (RAR-α), also known as NR1B1 (nuclear receptor subfamily 1, group B, member 1), is a nuclear receptor that in humans is encoded by the RARA gene.

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, a transcription factor. There are another two subtypes of RARs: beta and gamma subtypes.

Function

Retinoid signaling is transduced by two 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, 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, a derivative of vitamin A, which plays an important role in cell growth, differentiation, and the formation of organs in embryonic development.

Once retinoic acid binds to the RAR, the heterodimer initiates transcription and allows for its target genes to be expressed.  

Clinical significance

RA signaling has been correlated with several signaling pathways in early embryonic development. 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). 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 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.

Acute promyeloid leukemia

RARA plays an important role in the establishment of the immune system by inducing T-regulatory cells, promoting tolerance, and controlling the differentiation of immature immune cells in the bone marrow called promyelocytes into mature white blood cells. The prevalence of this gene in the developing immune system leaves it subject to possible defects, the most common of which is a condition known as acute promyeloid leukemia (APL), caused by a somatic mutation described by the fusion of RARA and the PML gene located on chromosome 15. This fusion results in the formation of the protein complex PML-RARα. Under normal circumstances, PML produces a tumor suppressing protein that works by inhibiting uncontrolled rapid cell growth. When the two proteins fuse together, their normal functions are hindered, resulting in the accumulation of promyelocytes in the bone marrow unable to differentiate past this immature phase. This fusion makes up for the cause of 98% of APL cases, with some other rare mutations and fusions making up the other 2%.6 Current treatment approaches include all-trans-retinoic acid (ATRA) which works by targeting and degrading the PML-RARα protein complex, in addition to chemotherapy and platelet transfusions.

Interactions

Retinoic acid receptor alpha has been shown to interact with:

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 three subtypes of RARs work redundantly.

Ligands

Antagonists

See also

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000131759Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000037992Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Giguere V, Ong ES, Segui P, Evans RM (1987). "Identification of a receptor for the morphogen retinoic acid". Nature. 330 (6149): 624–9. Bibcode:1987Natur.330..624G. doi:10.1038/330624a0. PMID 2825036. S2CID 4308015.
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  7. "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2021-04-27.
  8. ^ "OMIM Entry - * 180240 - RETINOIC ACID RECEPTOR, ALPHA; RARA". www.omim.org. Retrieved 2021-04-27.
  9. "Entrez Gene: retinoic acid receptor".
  10. ^ Kam RK, Deng Y, Chen Y, Zhao H (March 2012). "Retinoic acid synthesis and functions in early embryonic development". Cell & Bioscience. 2 (1): 11. doi:10.1186/2045-3701-2-11. PMC 3325842. PMID 22439772.
  11. Vitoux D, Nasr R, de The H (2007). "Acute promyelocytic leukemia: new issues on pathogenesis and treatment response". The International Journal of Biochemistry & Cell Biology. 39 (6): 1063–70. doi:10.1016/j.biocel.2007.01.028. PMID 17468032.
  12. Mora JR, Iwata M, von Andrian UH (September 2008). "Vitamin effects on the immune system: vitamins A and D take centre stage". Nat Rev Immunol. 8 (9): 685–98. doi:10.1038/nri2378. PMC 2906676. PMID 19172691.
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  20. Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961.
  21. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M (May 1999). "Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein". The Journal of Biological Chemistry. 274 (22): 15901–7. doi:10.1074/jbc.274.22.15901. PMID 10336495.
  22. Guidez F, Ivins S, Zhu J, Söderström M, Waxman S, Zelent A (April 1998). "Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia". Blood. 91 (8): 2634–42. doi:10.1182/blood.V91.8.2634.2634_2634_2642. PMID 9531570.
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  26. Farooqui M, Franco PJ, Thompson J, Kagechika H, Chandraratna RA, Banaszak L, Wei LN (February 2003). "Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity". Biochemistry. 42 (4): 971–9. doi:10.1021/bi020497k. PMID 12549917.
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Further reading

PDB gallery
  • 1dkf: CRYSTAL STRUCTURE OF A HETERODIMERIC COMPLEX OF RAR AND RXR LIGAND-BINDING DOMAINS 1dkf: CRYSTAL STRUCTURE OF A HETERODIMERIC COMPLEX OF RAR AND RXR LIGAND-BINDING DOMAINS
  • 1dsz: STRUCTURE OF THE RXR/RAR DNA-BINDING DOMAIN HETERODIMER IN COMPLEX WITH THE RETINOIC ACID RESPONSE ELEMENT DR1 1dsz: STRUCTURE OF THE RXR/RAR DNA-BINDING DOMAIN HETERODIMER IN COMPLEX WITH THE RETINOIC ACID RESPONSE ELEMENT DR1
  • 1hra: THE SOLUTION STRUCTURE OF THE HUMAN RETINOIC ACID RECEPTOR-BETA DNA-BINDING DOMAIN 1hra: THE SOLUTION STRUCTURE OF THE HUMAN RETINOIC ACID RECEPTOR-BETA DNA-BINDING DOMAIN
Transcription factors and intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies
Retinoid receptor modulators
RARTooltip Retinoic acid receptor
  • Retinoic acid metabolism inhibitors: Liarozole
RXRTooltip Retinoid X receptor
See also
Receptor/signaling modulators

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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