RARA

This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

Retinoic Acid Receptor Alpha

Receptor for retinoic acid (PubMed:19850744, PubMed:16417524, PubMed:20215566).
Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:28167758).
The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:28167758, PubMed:19398580).
In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (PubMed:16417524).
On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:9267036, PubMed:19850744, PubMed:20215566).
Formation of a complex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (PubMed:28167758).
Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (PubMed:28167758).
RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (By similarity).
Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (By similarity).
In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (By similarity).
In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (PubMed:28167758).
In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (PubMed:28167758).

Biological Process apoptotic cell clearanceManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process cellular response to estrogen stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process cellular response to lipopolysaccharideIEA:Ensembl
Biological Process cellular response to retinoic acidManual Assertion Based On ExperimentIMP:ARUK-UCL
Biological Process chondroblast differentiationIEA:Ensembl
Biological Process embryonic camera-type eye developmentIEA:Ensembl
Biological Process face developmentIEA:Ensembl
Biological Process female pregnancyIEA:Ensembl
Biological Process germ cell developmentIEA:Ensembl
Biological Process glandular epithelial cell developmentIEA:Ensembl
Biological Process growth plate cartilage developmentIEA:Ensembl
Biological Process hippocampus developmentIEA:Ensembl
Biological Process hormone-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process limb developmentIEA:Ensembl
Biological Process liver developmentIEA:Ensembl
Biological Process mRNA transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:ComplexPortal
Biological Process multicellular organism growthIEA:Ensembl
Biological Process negative regulation of cartilage developmentIEA:Ensembl
Biological Process negative regulation of cell population proliferationIEA:Ensembl
Biological Process negative regulation of granulocyte differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of interferon-gamma productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of miRNA transcriptionManual Assertion Based On ExperimentIMP:ARUK-UCL
Biological Process negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process neural tube closureIEA:Ensembl
Biological Process positive regulation of bindingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of cell cycleManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of interleukin-13 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of interleukin-4 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of interleukin-5 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of neuron differentiationIEA:Ensembl
Biological Process positive regulation of T-helper 2 cell differentiationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process prostate gland developmentIEA:Ensembl
Biological Process protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of apoptotic processIEA:Ensembl
Biological Process regulation of hematopoietic progenitor cell differentiationIEA:Ensembl
Biological Process regulation of myelinationIEA:Ensembl
Biological Process regulation of synaptic plasticityIEA:Ensembl
Biological Process response to cytokineIEA:Ensembl
Biological Process response to estradiolIEA:Ensembl
Biological Process response to ethanolIEA:Ensembl
Biological Process response to retinoic acidManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process response to vitamin AIEA:Ensembl
Biological Process retinoic acid receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process Sertoli cell fate commitmentIEA:Ensembl
Biological Process trachea cartilage developmentIEA:Ensembl
Biological Process ureteric bud developmentIEA:Ensembl
Biological Process ventricular cardiac muscle cell differentiationIEA:Ensembl

Nucleus
Cytoplasm
Nuclear localization depends on ligand binding, phosphorylation and sumoylation (PubMed:19850744).
Translocation to the nucleus in the absence of ligand is dependent on activation of PKC and the downstream MAPK phosphorylation (By similarity).
Increased nuclear localization upon pulsatile shear stress (PubMed:28167758).

Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation.

Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for transcriptional activity (By similarity).
Phosphorylation by AKT1 is required for the repressor activity but has no effect on DNA binding, protein stability nor subcellular localization. Phosphorylated by PKA in vitro. This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling.
Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated transcriptional activity.
Trimethylation enhances heterodimerization with RXRA and positively modulates the transcriptional activation.
Ubiquitinated.
Acetylated; acetylation is increased upon pulsatile shear stress and decreased upon oscillatory shear stress.