| Post Translational Modifications | 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 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. Phosphorylation at Ser-216 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity. Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO9 at Lys-227.leading to proteasomal degradation. |
| Function | 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 activation of 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 a 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. Independently of its methyltransferase activity, involved in replication fork progression: promotes PARP1 recruitment to replication forks, leading to poly-ADP-ribosylation of chromatin at replication forks and reduced fork speed. |
| Protein Name | Histone-Arginine Methyltransferase Carm1Coactivator-Associated Arginine Methyltransferase 1Protein Arginine N-Methyltransferase 4 |
| Database Links | Reactome: R-HSA-1368082Reactome: R-HSA-1368108Reactome: R-HSA-1989781Reactome: R-HSA-2151201Reactome: R-HSA-2426168Reactome: R-HSA-3214858Reactome: R-HSA-381340Reactome: R-HSA-400206Reactome: R-HSA-400253Reactome: R-HSA-6804114Reactome: R-HSA-9018519Reactome: R-HSA-9707564Reactome: R-HSA-9707616 |
| Cellular Localisation | NucleusCytoplasmChromosomeMainly Nuclear During The G1S And G2 Phases Of The Cell CycleCytoplasmic During MitosisAfter Breakup Of The Nuclear MembraneLocalizes To Replication Forks |
| Alternative Protein Names | Histone-Arginine Methyltransferase Carm1 proteinCoactivator-Associated Arginine Methyltransferase 1 proteinProtein Arginine N-Methyltransferase 4 proteinCARM1 proteinPRMT4 protein |
Information sourced from Uniprot.org
