Retinoids (RA) are metabolites of vitamin A (retinol) that are important signaling molecules during vertebrate development and tissue differentiation. RAs activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) nuclear transcription factor families. Most retinoid forms activate RAR family members, whereas RXR family members are activated by 9-cis-RA only. RAR family members, which include RARα, RARβ and RARγ, have a high affinity for all transretinoic acids and belong to the same class of nuclear transcription factors as thyroid hormone receptors, vitamin D3 receptor and ecdysone receptor. RAR isoforms are expressed in distinct patterns throughout development and in the mature organism. The human RARα gene maps to chromosome 17 and is implicated in the chromosomal translocation associated with acute promyelocytic leukemia (APL-M3). Specifically, the RARα gene is fused with the promyelocytic leukemia (PML) gene, which encodes the fusion protein PML/RARα. The PML/RARα fusion protein inhibits PML-dependent apoptotic pathways and halts myeloid differentiation at the promyelocytic stage.
Background References
1. Alotaibi H et al. Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription. Nucleic Acids Res 38:3172-85 (2010).
2. Pendino F et al. Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis. Blood 113:3172-81 (2009).
Sequence Similarity
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Tissue Specificity
Expressed in monocytes.
Post-translational Modification
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.
Western blot analysis of Retinoic Acid Receptor alpha on different lysates with Rabbit anti-Retinoic Acid Receptor alpha antibody (ET1611-77) at 1/1,000 dilution.
Lane 1: MCF7 cell lysate Lane 2: SK-Br-3 cell lysate Lane 3: HEK-293 cell lysate Lane 4: NIH/3T3 cell lysate Lane 5: PC-12 cell lysate
Lysates/proteins at 20 µg/Lane.
Predicted band size: 51 kDa Observed band size: 60 kDa
Exposure time: 1 minute 18 seconds; ECL: K1801;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (ET1611-77) at 1/1,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1/50,000 dilution was used for 1 hour at room temperature.
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