PRMT4/CARM1

PRMT4/CARM1

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. Acts as a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by enriching H3R17 methylation at its promoter, thereby positively regulating fatty acid synthesis (By similarity).

AgingIEA:Ensembl
Chromatin organizationIEA:UniProtKB-KW
Histone H3-R17 methylationISS:UniProtKB
Histone H3-R2 methylationManual Assertion Based On ExperimentIMP:UniProtKB
Histone methylationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of dendrite developmentIEA:Ensembl
Positive regulation of cell population proliferationIEA:Ensembl
Positive regulation of fat cell differentiationISS:UniProtKB
Regulation of intracellular estrogen receptor signaling pathwayISS:UniProtKB
Regulation of mRNA bindingIEA:Ensembl
Regulation of transcription, DNA-templatedISS:UniProtKB
Response to cAMPIEA:Ensembl

Nucleus
Cytoplasm
Mainly nuclear during the G1, S and G2 phases of the cell cycle (PubMed:19843527).
Cytoplasmic during mitosis, after breakup of the nuclear membrane (PubMed:19843527).

Auto-methylated on Arg-550. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing (By similarity).
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.