PRMT5

Description

The PRMT5 (protein arginine methyltransferase 5) is a protein-coding gene located on chromosome 14.

Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene. PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events. PRMT5 is a highly conserved arginine methyltransferase that translocated from the cytoplasm to the nucleus at embryonic day ~E8.5, and during preimplantation development at the ~4-cell stage.

== Interactions == Protein arginine methyltransferase 5 has been shown to interact with:

CLNS1A, Janus kinase 2, SNRPD3, SUPT5H, MEP50, RIOK1, COPR5. PRMT5 has been shown to interact with CLNS1A, RIOK1 and COPR5 through an interface created by a shallow groove located on the TIM barrel domain of PRMT5 and the consensus sequence GQF[D/E]DA[E/D] located in the terminal regions of the adaptor proteins. The characterisation of the interactions occurring in the binding groove between PRMT5 and peptides derived from the adaptor proteins lead to development of protein-protein interaction (PPI) inhibitors, modulating binding between PRMT5 and the adaptor proteins. Furthermore, Asberry and co-workers synthesised the first-in-class small molecule inhibitor of the PPI between PRMT5 and MEP50. The PPI inhibitors complement a plethora of compounds directly suppressing the enzymatic activity of PRMT5.

PRMT5 is an arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for MMA. It specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3), which is essential for the assembly and biogenesis of snRNP core particles. PRMT5 also methylates SUPT5H, potentially regulating its transcriptional elongation properties. It may methylate the N-terminal region of MBD2, mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro, and may play a role in cytokine-activated transduction pathways. PRMT5 negatively regulates cyclin E1 promoter activity and cellular proliferation. It methylates histone H2A and H4 'Arg-3' during germ cell development and histone H3 'Arg-8', which may repress transcription. PRMT5 methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), a process required for their interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage. It also methylates RPS10, attenuates EGF signaling through the MAPK1/MAPK3 pathway, and is required for induction of E-selectin and VCAM-1 on the endothelial cells surface at sites of inflammation. PRMT5 methylates HOXA9, regulates SRGAP2 involved in cell migration and differentiation, and acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1. It methylates GM130/GOLGA2, regulating Golgi ribbon formation, and methylates H4R3 in genes involved in glioblastomagenesis. PRMT5 symmetrically methylates POLR2A, allowing the recruitment of proteins including SMN1/SMN2 and SETX, which is necessary for resolving RNA-DNA hybrids created by RNA polymerase II. It binds the promoter of gamma-globin HBG1/HBG2 and represses its expression, and symmetrically methylates NCL. PRMT5 methylates p53/TP53, potentially affecting its target gene specificity, and is involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes. It forms homodimers and homotetramers, and is a component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A. PRMT5 interacts with numerous proteins, including EGFR, HOXA9, SRGAP2, CHTOP, EPB41L3, JAK2, SSTR1, SUPT5H, BRAF, RAF1, LSM11, PRMT7, SNRPD3, COPRS, CLNS1A/pICln, RPS10, WDR77, IWS1, CRY1, POLR2A, SMN1/SMN2, LYAR, TTC5/STRAP, p53/TP53, FAM47E, TDRD6, STUB1, MBD2, and PRDM1.

PRMT5 is also known as HRMT1L5, HSL7, IBP72, JBP1, SKB1, SKB1Hs.

Associated Diseases

WES Whole Exome Sequencing