The fragile X mental retardation protein, FMRP, is subject to post-translational phosphorylation and arginine methylation. Both modifications map to amino acids encoded by exon 15 of the human FMR1 gene. Furthermore, both modifications have been shown to play important roles in the normal functioning of FMRP, although the kinase(s) and methyltransferase(s) responsible for them have yet to be identified. Methylation influences FMRP’s dimerization-state and its ability to bind mRNA, while phosphorylation appears to control the translatability of FMRP bound mRNAs. In addition, FMR1 exon 15 is subject to alternative splicing. This, results in variants that lack the conserved serine phosphorylation site and a single arginine that lies within a conformational switch region, suggesting that these residues may play unique and/or synergistic roles in the function of FMRP.
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