功能 |
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.
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總結(jié) |
CARM1 (coactivator-associated arginine methyltransferase 1), also known as protein arginine N-methyltransferase 4 (PRMT4), is a 585 amino acid nuclear and cytoplasmic protein belonging to the protein arginine N-methyltransferase family. As a protein arginine N-methyltransferase, CARM1 is capable of catalyzing the transfer of methyl groups from S-adenosylmethionine to the guanidino group nitrogen atoms of arginine residues in certain proteins involved in mRNA stability, DNA packaging and transcriptional regulation. The methyltransferase activity of CARM1 has been found to be negatively regulated through phosphorylation at a conserved serine residue. CARM1 acts as a positive regulator for multiple transcription factors and functions as a secondary coactivator through its association with p160 coactivators. CARM1 exists as two alternatively spliced isoforms, and is encoded by a gene that maps to human chromosome 19p13.2.
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別名 |
CARM1, CARM-1, Coactivator-Associated Arginine Methyltransferase 1, PRMT4, Protein Arginine N-methyltransferase 4
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