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Overview

Uniprot IDO14744
Protein NameProtein arginine N-methyltransferase 5
Gene NamePRMT5
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
240 TSIFLTNKKGFPVLS
241 SIFLTNKKGFPVLSK

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:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951). 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:11747828, PubMed:12411503, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). 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:21258366, PubMed:21917714). 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)

Protein Sequence

10 MAAMAVGGAG 20 GSRVSSGRDL 30 NCVPEIADTL 40 GAVAKQGFDF 50 LCMPVFHPRF 60 KREFIQEPAK 70 NRPGPQTRSD 80 LLLSGRDWNT 90 LIVGKLSPWI 100 RPDSKVEKIR 110 RNSEAAMLQE 120 LNFGAYLGLP 130 AFLLPLNQED 140 NTNLARVLTN 150 HIHTGHHSSM 160 FWMRVPLVAP 170 EDLRDDIIEN 180 APTTHTEEYS 190 GEEKTWMWWH 200 NFRTLCDYSK 210 RIAVALEIGA 220 DLPSNHVIDR 230 WLGEPIKAAI 240 LPTSIFLTNK 250 KGFPVLSKMH 260 QRLIFRLLKL 270 EVQFIITGTN 280 HHSEKEFCSY 290 LQYLEYLSQN 300 RPPPNAYELF 310 AKGYEDYLQS 320 PLQPLMDNLE 330 SQTYEVFEKD 340 PIKYSQYQQA 350 IYKCLLDRVP 360 EEEKDTNVQV 370 LMVLGAGRGP 380 LVNASLRAAK 390 QADRRIKLYA 400 VEKNPNAVVT 410 LENWQFEEWG 420 SQVTVVSSDM 430 REWVAPEKAD 440 IIVSELLGSF 450 ADNELSPECL 460 DGAQHFLKDD 470 GVSIPGEYTS 480 FLAPISSSKL 490 YNEVRACREK 500 DRDPEAQFEM 510 PYVVRLHNFH 520 QLSAPQPCFT 530 FSHPNRDPMI 540 DNNRYCTLEF 550 PVEVNTVLHG 560 FAGYFETVLY 570 QDITLSIRPE 580 THSPGMFSWF 590 PILFPIKQPI 600 TVREGQTICV 610 RFWRCSNSKK 620 VWYEWAVTAP 630 VCSAIHNPTG RSYTIGL

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005794 Golgi apparatus
Cellular Component GO:0035097 histone methyltransferase complex
Cellular Component GO:0034709 methylosome
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0070888 E-box binding
Molecular Function GO:0140938 histone H3 methyltransferase activity
Molecular Function GO:0044020 histone H4R3 methyltransferase activity
Molecular Function GO:0042054 histone methyltransferase activity
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0008327 methyl-CpG binding
Molecular Function GO:0008168 methyltransferase activity
Molecular Function GO:0002039 p53 binding
Molecular Function GO:0046982 protein heterodimerization activity
Molecular Function GO:0016274 protein-arginine N-methyltransferase activity
Molecular Function GO:0035243 protein-arginine omega-N symmetric methyltransferase activity
Molecular Function GO:0043021 ribonucleoprotein complex binding
Molecular Function GO:0003714 transcription corepressor activity
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0006353 DNA-templated transcription termination
Biological Process GO:0042118 endothelial cell activation
Biological Process GO:0090161 Golgi ribbon formation
Biological Process GO:0097421 liver regeneration
Biological Process GO:0045596 negative regulation of cell differentiation
Biological Process GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
Biological Process GO:0018216 peptidyl-arginine methylation
Biological Process GO:0035246 peptidyl-arginine N-methylation
Biological Process GO:1904992 positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
Biological Process GO:0048026 positive regulation of mRNA splicing, via spliceosome
Biological Process GO:0048714 positive regulation of oligodendrocyte differentiation
Biological Process GO:2000234 positive regulation of rRNA processing
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0070372 regulation of ERK1 and ERK2 cascade
Biological Process GO:0007088 regulation of mitotic nuclear division
Biological Process GO:1901796 regulation of signal transduction by p53 class mediator
Biological Process GO:0000387 spliceosomal snRNP assembly

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.