Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.
Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia.
Belongs to the protein arginine N-methyltransferase family.
Auto-methylated on Arg-550. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing. Phosphorylation at Ser-216 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity (By similarity). Phosphorylation at Ser-216 is strongly increased during mitosis, and decreases rapidly to a very low, basal level after entry into the G1 phase of the cell cycle. Phosphorylation at Ser-216 may promote location in the cytosol.
Nucleus. Cytoplasm. Mainly nuclear during the G1, S and G2 phases of the cell cycle. Cytoplasmic during mitosis, after breakup of the nuclear membrane.