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MGP004267

UniProt Annotations

Entry Information
Gene Namecoactivator-associated arginine methyltransferase 1
Protein EntryCARM1_HUMAN
UniProt IDQ86X55
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=3; IsoId=Q86X55-3; Sequence=Displayed; Name=1; IsoId=Q86X55-1; Sequence=VSP_039876; Name=2; IsoId=Q86X55-2; Sequence=VSP_012506, VSP_012507; Note=No experimental confirmation available.;
Catalytic ActivityS-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone]. {ECO:0000269|PubMed:19405910}.
Enzyme RegulationMethylation 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. {ECO:0000250}.
FunctionMethylates (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. {ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:19405910}.
InteractionP17676:CEBPB; NbExp=2; IntAct=EBI-2339854, EBI-969696; Q05826:CEBPB (xeno); NbExp=3; IntAct=EBI-2339854, EBI-7774198; Q96EY1:DNAJA3; NbExp=2; IntAct=EBI-2339854, EBI-356767; O43809:NUDT21; NbExp=2; IntAct=EBI-2339854, EBI-355720; Q96PU8:QKI; NbExp=2; IntAct=EBI-2339854, EBI-945792; Q92922:SMARCC1; NbExp=4; IntAct=EBI-2339854, EBI-355653;
PtmAuto-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). {ECO:0000250}.
PtmPhosphorylation 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. {ECO:0000250, ECO:0000269|PubMed:19843527}.
SimilarityBelongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N- methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU01015}.
SimilarityContains 1 SAM-dependent MTase PRMT-type domain. {ECO:0000255|PROSITE-ProRule:PRU01015}.
Subcellular LocationNucleus. Cytoplasm. Note=Mainly nuclear during the G1, S and G2 phases of the cell cycle. Cytoplasmic during mitosis, after breakup of the nuclear membrane.
SubunitHomodimer (Probable). 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 SNRPC (By similarity). Interacts with NR1H4. Interacts with RELA. Interacts with HTLV-1 Tax-1. {ECO:0000250, ECO:0000269|PubMed:15471871, ECO:0000269|PubMed:16497732, ECO:0000269|PubMed:17005681, ECO:0000269|PubMed:21410432, ECO:0000305}.
Tissue SpecificityOverexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia. {ECO:0000269|PubMed:15221992}.
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