Protein arginine N-methyltransferase 5

UniProt O14744 Organism Homo sapiens Gene HRMT1L5, IBP72, JBP1, PRMT5, SKB1 EC 2.1.1.320

Also known as: HRMT1L5, IBP72, JBP1, PRMT5, SKB1

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. 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. Methylates SUPT5H and may regulate its transcriptional elongation properties. May methylate the N-terminal region of MBD2. 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. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity. Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation. 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. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. 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. Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression. Symmetrically methylates NCL. Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity. 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).

Classification

Family (Pfam): PF05185 PRMT5, PF17286 PRMT5_C, PF17285 PRMT5_TIM
InterPro: Arg_MeTrfase, Arg_MeTrfase_PRMT5, PRMT5, PRMT5_C, PRMT5_TIM, SAM-dependent_MTases_sf
Functional cluster: Nucleotide & Amino-Acid Biosynthesis Enzymes

Experimental structures · PDB · 84

4GQB X-ray 2.06A
4X60 X-ray 2.35A
4X61 X-ray 2.85A
4X63 X-ray 3.05A
5C9Z X-ray 2.36A
5EMJ X-ray 2.27A
5EMK X-ray 2.52A
5EML X-ray 2.39A
5EMM X-ray 2.37A
5FA5 X-ray 2.34A
6CKC X-ray 2.80A
6K1S X-ray 2.60A
… and 72 more

A predicted model is available from AlphaFold.

Gene Ontology · 40

Drugs targeting this protein · 1

PEMRAMETOSTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Coordinator of PRMT5 and differentiation stimulator 1 shared papers
Somatostatin receptor type 1 1 shared papers
Methylosome protein WDR77 6 shared papers
Protein IWS1 homolog 1 shared papers
Band 4.1-like protein 3 1 shared papers
SLIT-ROBO Rho GTPase-activating protein 2 1 shared papers
Homeobox protein Hox-A9 1 shared papers
Methylosome subunit pICln 4 shared papers
Protein FAM47E 1 shared papers
Golgin subfamily A member 2 1 shared papers
Cell growth-regulating nucleolar protein 1 shared papers
Protein arginine N-methyltransferase skb1 1 shared papers

Literature · 39 cited papers

The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions. Life. Sci Alliance · 2021
SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination. Nature · 2016
5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex. Cell Rep. · 2014
Human fetal globin gene expression is regulated by LYAR. Nucleic Acids Res. · 2014
Crystal structure of the human PRMT5:MEP50 complex. Proc. Natl. Acad. Sci. U.S.A. · 2012
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
HOXA9 methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules. Mol. Cell. Biol. · 2012
Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci. Signal. · 2011
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat. Cell Biol. · 2011
RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. J. Biol. Chem. · 2011
… and 27 more in the literature graph

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