Function
Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4, SERBP1, RBM15, FOXO1, CHTOP and MAP3K5/ASK1 (PubMed:10749851, PubMed:16879614, PubMed:26876602, PubMed:22095282, PubMed:26575292, PubMed:18951090, PubMed:25284789).
Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates RBM15, promoting ubiquitination and degradation of RBM15 (PubMed:26575292).
Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity (PubMed:18951090).
Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity (PubMed:25284789).
Methylates MAP3K5/ASK1 at 'Arg-78' and 'Arg-80' which promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 stimulation and MAP3K5-induced activation of JNK (PubMed:22095282).
Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789).
Plays a role in regulating alternative splicing in the heart (By similarity).
Biological Process
Cardiac muscle tissue developmentISS:UniProtKB
Cell surface receptor signaling pathwayManual Assertion Based On ExperimentTAS:ProtInc
Histone H4-R3 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone methylationManual Assertion Based On ExperimentIDA:UniProtKB
In utero embryonic developmentIEA:Ensembl
Negative regulation of JNK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of megakaryocyte differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Neuron projection developmentManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-arginine methylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of erythrocyte differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of hemoglobin biosynthetic processISS:BHF-UCL
Positive regulation of p38MAPK cascadeISS:BHF-UCL
Protein homooligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein methylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of megakaryocyte differentiationManual Assertion Based On ExperimentIDA:UniProtKB
RNA splicingISS:UniProtKB
Viral protein processingTAS:Reactome
Cellular Location
Nucleus
Nucleus, nucleoplasm
Cytoplasm
Cytoplasm, cytosol
Mostly found in the cytoplasm. Colocalizes with CHTOP within the nucleus. Low levels detected also in the chromatin fraction (By similarity).
PTM
Polyubiquitinated at Lys-145 by the SCF(FBXL17) complex, leading to its subsequent degradation (By similarity).
Ubiquitination is regulated by acetylation at Lys-228 and Lys-233 (By similarity).
Polyubiquitinated by E3 ubiquitin-protein ligase TRIM48, leading to suppression of MAP3K5/ASK1 methylation and subsequent MAP3K5 activation (PubMed:29186683).
Acetylation at Lys-228 and Lys-233 regulates ubiquitination by the SCF(FBXL17) complex. Acetylated at Lys-233 by p300/EP300. Deacetylated at Lys-228 and Lys-233 by SIRT1.