ID:CARM1_HUMAN DESCRIPTION: RecName: Full=Histone-arginine methyltransferase CARM1; EC=2.1.1.-; EC=2.1.1.125; AltName: Full=Coactivator-associated arginine methyltransferase 1; AltName: Full=Protein arginine N-methyltransferase 4; 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 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. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + arginine-[histone] = S-adenosyl-L-homocysteine + N(omega)-methyl-arginine-[histone]. 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 (By similarity). SUBUNIT: Homodimer (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. 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. TISSUE SPECIFICITY: Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia. PTM: 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). PTM: 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. SIMILARITY: Belongs to the protein arginine N-methyltransferase family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q86X55
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC156435 - Synthetic construct Homo sapiens clone IMAGE:100062976, MGC:190647 coactivator-associated arginine methyltransferase 1 (CARM1) mRNA, encodes complete protein. BC172490 - Synthetic construct Homo sapiens clone IMAGE:100069184, MGC:199195 coactivator-associated arginine methyltransferase 1 (CARM1) mRNA, encodes complete protein. AL833242 - Homo sapiens mRNA; cDNA DKFZp761A1520 (from clone DKFZp761A1520). JC506674 - Sequence 42 from Patent EP2733220. JC737786 - Sequence 42 from Patent WO2014075939. JC506688 - Sequence 56 from Patent EP2733220. JC737800 - Sequence 56 from Patent WO2014075939. JC506674 - Sequence 42 from Patent EP2733220. JC737786 - Sequence 42 from Patent WO2014075939. JC506661 - Sequence 29 from Patent EP2733220. JC737773 - Sequence 29 from Patent WO2014075939. JC506688 - Sequence 56 from Patent EP2733220. JC737800 - Sequence 56 from Patent WO2014075939. JC506666 - Sequence 34 from Patent EP2733220. JC737778 - Sequence 34 from Patent WO2014075939. BC046240 - Homo sapiens coactivator-associated arginine methyltransferase 1, mRNA (cDNA clone IMAGE:4859203), partial cds. AF055027 - Homo sapiens clone 24658 mRNA sequence. BC036886 - Homo sapiens coactivator-associated arginine methyltransferase 1, mRNA (cDNA clone IMAGE:5399617), partial cds. JD389923 - Sequence 370947 from Patent EP1572962. BC070496 - Homo sapiens cDNA clone IMAGE:6094041, partial cds. JD451649 - Sequence 432673 from Patent EP1572962. JD124845 - Sequence 105869 from Patent EP1572962. JD129186 - Sequence 110210 from Patent EP1572962. JD493762 - Sequence 474786 from Patent EP1572962. JD365871 - Sequence 346895 from Patent EP1572962. JD519032 - Sequence 500056 from Patent EP1572962. JD392014 - Sequence 373038 from Patent EP1572962. JD226450 - Sequence 207474 from Patent EP1572962. JD192693 - Sequence 173717 from Patent EP1572962. JD518843 - Sequence 499867 from Patent EP1572962. JD392302 - Sequence 373326 from Patent EP1572962. JD455405 - Sequence 436429 from Patent EP1572962. JD445302 - Sequence 426326 from Patent EP1572962. JD398293 - Sequence 379317 from Patent EP1572962. JD152107 - Sequence 133131 from Patent EP1572962. JD142269 - Sequence 123293 from Patent EP1572962. JD424282 - Sequence 405306 from Patent EP1572962. JD161273 - Sequence 142297 from Patent EP1572962. DQ582098 - Homo sapiens piRNA piR-32210, complete sequence. JD076059 - Sequence 57083 from Patent EP1572962. JD173559 - Sequence 154583 from Patent EP1572962. JD390892 - Sequence 371916 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_carm1Pathway - Transcription Regulation by Methyltransferase of CARM1 h_vdrPathway - Control of Gene Expression by Vitamin D Receptor h_carm-erPathway - CARM1 and Regulation of the Estrogen Receptor h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology
Reactome (by CSHL, EBI, and GO)
Protein Q86X55 (Reactome details) participates in the following event(s):
R-HSA-3215152 TP53 in complex with EP300, PRMT1 and CARM1 binds the GADD45A promoter R-HSA-9009526 CARM1 binds TBP:TFIIA:DDX5:ESR1:estrogen:TFF1 gene R-HSA-400143 Fatty acid ligands activate PPARA R-HSA-5205822 CARM1 methylates arginine-18 (H3R17) of histone H3 R-HSA-5229010 CARM1 methylates arginine-27 of histone H3 (H3R26) R-HSA-9023860 Histone acetyltransferases are recruited to the TFF1 gene R-HSA-5205824 CARM1, PRMT6 methylate arginine-3 of histone H3 (H3R2) R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-9018519 Estrogen-dependent gene expression R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-8939211 ESR-mediated signaling R-HSA-3214858 RMTs methylate histone arginines R-HSA-556833 Metabolism of lipids R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-9006931 Signaling by Nuclear Receptors R-HSA-3247509 Chromatin modifying enzymes R-HSA-1430728 Metabolism R-HSA-212436 Generic Transcription Pathway R-HSA-162582 Signal Transduction R-HSA-4839726 Chromatin organization R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)