Protein arginine N-methyltransferase 1 (PRMT1) is a member of the protein arginine N-methyltransferase (PRMT) family of proteins that catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) to a guanidine nitrogen of arginine. Though all PRMT proteins catalyze the formation of mono-methyl arginine, Type I PRMTs (PRMT1, 3, 4, and 6) add an additional methyl group to produce an asymmetric di-methyl arginine while Type II PRMTs (PRMT 5 and 7) produce symmetric di-methyl arginine. Mono-methyl arginine, but not di-methyl arginine, can be converted to citrulline through deimination catalyzed by enzymes such as PADI4 . Most PRMTs, including PRMT1, methylate arginine residues found within glycine-arginine rich (GAR) protein domains, such as RGG, RG, and RXR repeats. However, PRMT4/CARM1 and PRMT5 methylate arginine residues within PGM (proline-, glycine-, methionine-rich) motifs. PRMT1 methylates Arg3 of histone H4 and cooperates synergistically with p300/CBP to enhance transcriptional activation by nuclear receptor proteins. In addition, PRMT1 methylates many non-histone proteins, including the orphan nuclear receptor HNF4, components of the heterogeneous nuclear ribonucleoprotein (hnRNP) particle, the RNA binding protein Sam68, interleukin enhancer-binding factor 3 (ILF3) and interferon-alpha and beta receptors. These interactions suggest additional functions in transcriptional regulation, mRNA processing and signal transduction. Alternative mRNA splicing produces three enzymatically active PRMT1 isoforms that differ in their amino-terminal regions. PRMT1 is localized to the nucleus or cytoplasm, depending on cell type, and appears in many distinct protein complexes. ILF3, TIS21 and the leukemia-associated BTG1 proteins bind PRMT1 to regulate its methyltransferase activity.
