LMP013496 UniProt Annotations
Gene Name coactivator-associated arginine methyltransferase 1
Protein Entry CARM1_RAT
UniProt ID Q4AE70
Species Rat
Comment type Description
Alternative Products Event=Alternative splicing; Named isoforms=4; Comment=Named isoforms=2.; Name=1; Synonyms=CARM1-v2; IsoId=Q4AE70-1; Sequence=Displayed; Name=2; Synonyms=CARM1-v1; IsoId=Q4AE70-2; Sequence=VSP_020384; Name=3; Synonyms=CARM1-v3; IsoId=Q4AE70-3; Sequence=VSP_020382, VSP_020385; Name=4; Synonyms=CARM1-v4; IsoId=Q4AE70-4; Sequence=VSP_020383;
Catalytic Activity S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone].
Developmental Stage Isoforms 2 and 3 are expressed in fetal brain
Enzyme Regulation Methylation of H3R17 (H3R17me) by CARM1 is stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23' (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17' (H3R17ci) by PADI4
Function Isoform 3 specifically affects pre-mRNA splicing. This activity is independent from methyltransferase activity
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 activates 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
Ptm Auto-methylated on Arg-551. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing (By similarity)
Ptm Phosphorylation at Ser-217 interferes with S-adenosyl-L- methionine binding and strongly reduces methyltransferase activity. Phosphorylation at Ser-217 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- 217 may promote location in the cytosol (By similarity)
Similarity Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N- methyltransferase family
Similarity Contains 1 SAM-dependent MTase PRMT-type domain
Subcellular Location Nucleus . Cytoplasm . Note=Mainly nuclear during the G1, S and G2 phases of the cell cycle. Cytoplasmic during mitosis, after breakup of the nuclear membrane (By similarity)
Subunit Homodimer (Probable). Interacts with NR1H4. Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1. Part of a complex consisting of CARM1, EP300/P300 and NCOA2/GRIP1. Interacts with FLII, TP53, myogenic factor MEF2, EP300/P300, TRIM24, CREBBP and CTNNB1. Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1. Interacts with NCOA3/SRC3. Interacts with RELA (By similarity). Interacts with SNRPC. {ECO:0000250, ECO:0000269|PubMed:15944154, ECO:0000269|PubMed:17882262, ECO:0000305}.
Tissue Specificity Isoform 1 is expressed at low levels in brain, liver and testis. Isoform 2 is highly expressed in brain, liver, skeletal muscle and testis. Isoform 3 is highly expressed in spleen, liver and kidney. Isoform 4 is expressed in spleen, liver and kidney
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