| Comment type | Description |
|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=Alpha-1; IsoId=P11416-1; Sequence=Displayed; Name=Alpha-2; IsoId=P11416-2; Sequence=VSP_003630; |
| Disruption Phenotype | Seminiferous tubules of 6 month-old animals display varying degrees of testicular degeneration, with moderate to severe levels of germ-cell degeneration. Epithelial cells in the epididymis show general disorganization. Sperm count is reduced to about 1.7% of wild-type and sperm mobility reduced by half. Rara and Rarg, but not Rara and Rarb, double knockout mice exhibit growth retardation after 3 weeks. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed. {ECO:0000269|PubMed:15901285, ECO:0000269|PubMed:17905941, ECO:0000269|PubMed:19389355}. |
| Domain | Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. |
| Function | Receptor for retinoic acid. 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. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing KMT2E/MLL5. Mediates retinoic acid-induced granulopoiesis. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function. {ECO:0000269|PubMed:10660575, ECO:0000269|PubMed:15901285, ECO:0000269|PubMed:17205979, ECO:0000269|PubMed:17905941, ECO:0000269|PubMed:19078967, ECO:0000269|PubMed:19389355, ECO:0000269|PubMed:9230306}. |
| Induction | By retinoic acid. {ECO:0000269|PubMed:17905941}. |
| Interaction | Q8C050:Rps6ka5; NbExp=2; IntAct=EBI-346736, EBI-8391218; |
| Ptm | Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for the N-terminal AF1 transcriptional activity. Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation. Phosphorylation by AKT1 inhibits the transactivation activity. On retinoic acid stimulation, phosphorylation on Ser-369 by RPS6KA5 promotes interaction with GTF2H3 and the CDK7-mediated phosphorylation of Ser-77. {ECO:0000269|PubMed:12079996, ECO:0000269|PubMed:19078967, ECO:0000269|PubMed:9230306}. |
| Ptm | 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 (By similarity). {ECO:0000250}. |
| Similarity | Belongs to the nuclear hormone receptor family. NR1 subfamily. {ECO:0000305}. |
| Similarity | Contains 1 nuclear receptor DNA-binding domain. {ECO:0000255|PROSITE-ProRule:PRU00407}. |
| Subcellular Location | Nucleus. Cytoplasm. Note=Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus is dependent on activation of PKC and the downstream MAPK phosphorylation. |
| Subunit | Interacts with PRMT2 (By similarity). Interacts with LRIF1 (By similarity). Interacts with NCOA7 in a ligand-inducible manner. Interacts with KMT2E/MLL5. Interacts (via the ligand- binding domain) with PRAME; interaction is direct and ligand (retinoic acid)-dependent. Interacts with PRKAR1A; the interaction negatively. regulates RARA transcriptional activity. Interacts with NCOR1 and NCOR2; the interaction occurs in the absence of ligand and represses transciptional activity. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with CDK7; the interaction is enhanced by interaction with GTF2H3. Interacts with GTF2H3; the interaction requires prior phosphorylation on Ser-369 which then enhances interaction with CDK7. Interacts with ASXL1 and NCOA1 (By similarity). {ECO:0000250}. |
| Tissue Specificity | Expressed in Sertoli cells and germ cells. {ECO:0000269|PubMed:17905941}. |