PRMT5
PRMT5 is an enzyme that belongs to the methyltransferase family. The encoded protein catalyzes the transfer of methyl groups to the amino acid arginine, in target proteins that include histones, transcriptional elongation factors and the tumor suppressor p53. This gene plays a role in several cellular processes, including transcriptional regulation, and the assembly of small nuclear ribonucleoproteins.
Function
Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503).
Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828, PubMed:17709427).
Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890).
Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity).
Methylates histone H3 'Arg-8', which may repress transcription (By similarity).
Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity).
Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21917714, PubMed:21258366).
Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714).
Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951).
Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653).
Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity).
Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892).
Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789).
Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805).
Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918).
Symmetrically methylates NCL (PubMed:21081503).
Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621).
Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity).
Biological Process
Chromatin organizationIEA:UniProtKB-KW
Circadian regulation of gene expressionISS:UniProtKB
DNA-templated transcription, terminationManual Assertion Based On ExperimentIMP:UniProtKB
Endothelial cell activationManual Assertion Based On ExperimentIMP:UniProtKB
Golgi ribbon formationManual Assertion Based On ExperimentIMP:UniProtKB
Histone arginine methylationManual Assertion Based On ExperimentIBA:GO_Central
Histone H4-R3 methylationManual Assertion Based On ExperimentIDA:WormBase
Liver regenerationIEA:Ensembl
Negative regulation of cell differentiationIEA:Ensembl
Peptidyl-arginine methylationManual Assertion Based On ExperimentIMP:UniProtKB
Peptidyl-arginine N-methylationManual Assertion Based On ExperimentIDA:WormBase
Positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathwayManual Assertion Based On ExperimentIGI:WormBase
Positive regulation of mRNA splicing, via spliceosome1 PublicationIC:ComplexPortal
Positive regulation of oligodendrocyte differentiationIEA:Ensembl
Regulation of DNA methylationIEA:Ensembl
Regulation of ERK1 and ERK2 cascadeIEA:Ensembl
Regulation of mitotic nuclear divisionManual Assertion Based On ExperimentTAS:ProtInc
Regulation of signal transduction by p53 class mediatorTAS:Reactome
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIBA:GO_Central
Spliceosomal snRNP assemblyManual Assertion Based On ExperimentIMP:UniProtKB