protein methyltransferases


Summary: Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.

Top Publications

  1. Migliori V, Müller J, Phalke S, Low D, Bezzi M, Mok W, et al. Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance. Nat Struct Mol Biol. 2012;19:136-44 pubmed publisher
    ..Our findings identify H3R2me2s as a previously unknown mark that keeps genes poised in euchromatin for transcriptional activation upon cell-cycle withdrawal and differentiation in human cells. ..
  2. Copeland R. Molecular pathways: protein methyltransferases in cancer. Clin Cancer Res. 2013;19:6344-50 pubmed publisher
    The protein methyltransferases (PMT) constitute a large and important class of enzymes that catalyze site-specific methylation of lysine or arginine residues on histones and other proteins...
  3. Willnow S, Martin M, Luscher B, Weinhold E. A selenium-based click AdoMet analogue for versatile substrate labeling with wild-type protein methyltransferases. Chembiochem. 2012;13:1167-73 pubmed publisher
    Protein methylation is catalyzed by S-adenosyl-L-methionine-dependent protein methyltransferases (MTases), and this posttranslational modification serves diverse cellular functions...
  4. Huang J, Vogel G, Yu Z, Almazan G, Richard S. Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation. J Biol Chem. 2011;286:44424-32 pubmed publisher
    ..Our findings define a role of PRMT5 in glial cell differentiation and link PRMT5 to epigenetic changes during oligodendrocyte differentiation. ..
  5. Kirino Y, Kim N, De Planell Saguer M, Khandros E, Chiorean S, Klein P, et al. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat Cell Biol. 2009;11:652-8 pubmed publisher
    ..Our findings underscore the significance of sDMA modification of Piwi proteins in the germline and suggest an interacting pathway of genes that are required for piRNA function and PGC specification. ..
  6. Wysocka J, Allis C, Coonrod S. Histone arginine methylation and its dynamic regulation. Front Biosci. 2006;11:344-55 pubmed
    ..Given the surge of interest in histone arginine methylation, this review article will focus on recent progress in this area. ..
  7. Krivtsov A, Armstrong S. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007;7:823-33 pubmed
    ..The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development. ..
  8. Li H, Rauch T, Chen Z, SZABO P, Riggs A, Pfeifer G. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006;281:19489-500 pubmed
  9. Jelinic P, Stehle J, Shaw P. The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation. PLoS Biol. 2006;4:e355 pubmed
    ..These results suggest that CTCFL and PRMT7 may play a role in male germline imprinted gene methylation. ..

More Information


  1. Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S, et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008;40:897-903 pubmed publisher
    ..Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation. ..
  2. Loyola A, Tagami H, Bonaldi T, Roche D, Quivy J, Imhof A, et al. The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep. 2009;10:769-75 pubmed publisher
  3. Mora L, Heurgué Hamard V, de Zamaroczy M, Kervestin S, Buckingham R. Methylation of bacterial release factors RF1 and RF2 is required for normal translation termination in vivo. J Biol Chem. 2007;282:35638-45 pubmed
    ..This suggests that the expression of some genes needed for optimal growth under such conditions can become growth limiting as a result of inefficient translation termination. ..
  4. Krichevsky A, Gutgarts H, Kozlovsky S, Tzfira T, Sutton A, Sternglanz R, et al. C2H2 zinc finger-SET histone methyltransferase is a plant-specific chromatin modifier. Dev Biol. 2007;303:259-69 pubmed
    ..Thus, AtSWP1 and AtCZS represent two main components of a co-repressor complex that fine tunes flowering and is unique to plants. ..
  5. Cheng D, Cote J, Shaaban S, Bedford M. The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol Cell. 2007;25:71-83 pubmed
  6. Esteve P, Chin H, Smallwood A, Feehery G, Gangisetty O, Karpf A, et al. Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication. Genes Dev. 2006;20:3089-103 pubmed
    ..Thus, direct cooperation between DNMT1 and G9a provides a mechanism of coordinated DNA and H3K9 methylation during cell division. ..
  7. Couture J, Collazo E, Hauk G, Trievel R. Structural basis for the methylation site specificity of SET7/9. Nat Struct Mol Biol. 2006;13:140-6 pubmed
    ..Among the putative targets is TAF7, which is methylated at Lys5 by the enzyme in vitro. These results demonstrate the predictive value of the consensus motif in identifying novel substrates for SET7/9. ..
  8. Hayashi K, Yoshida K, Matsui Y. A histone H3 methyltransferase controls epigenetic events required for meiotic prophase. Nature. 2005;438:374-8 pubmed
    ..These findings indicate that meiosis-specific epigenetic events in mammals are crucial for proper meiotic progression. ..
  9. Cho S, Park J, Kang Y. Dual functions of histone-lysine N-methyltransferase Setdb1 protein at promyelocytic leukemia-nuclear body (PML-NB): maintaining PML-NB structure and regulating the expression of its associated genes. J Biol Chem. 2011;286:41115-24 pubmed publisher
    ..Our findings suggest that Setdb1 performs dual, but inseparable, functions at PML-NBs to maintain the structural integrity of PML-NBs and to control PML-NB-associated genes transcriptionally. ..
  10. Ceol C, Houvras Y, Jane Valbuena J, Bilodeau S, Orlando D, Battisti V, et al. The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature. 2011;471:513-7 pubmed publisher
    ..Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis. ..
  11. Hayashi K, de Sousa Lopes S, Surani M. Germ cell specification in mice. Science. 2007;316:394-6 pubmed
    ..Blimp1 may also have a role in the maintenance of early germ cell characteristics by ensuring their escape from the somatic fate as well as possible reversion to pluripotent stem cells. ..
  12. Majumder S, Alinari L, Roy S, Miller T, Datta J, SIF S, et al. Methylation of histone H3 and H4 by PRMT5 regulates ribosomal RNA gene transcription. J Cell Biochem. 2010;109:553-63 pubmed publisher
    ..These data suggest a key role of PRMT5 and the two methylated histones in regulating rRNA promoter activity. ..
  13. Yuan P, Han J, Guo G, Orlov Y, Huss M, Loh Y, et al. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev. 2009;23:2507-20 pubmed publisher
    ..Our results suggest that Eset restricts the extraembryonic trophoblast lineage potential of pluripotent cells and links an epigenetic regulator to key cell fate decision through a pluripotency factor. ..
  14. Yang X, Huang B, Li M, Lamb A, Kelleher N, Chen L. Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit. EMBO J. 2009;28:1055-66 pubmed publisher
    ..Together, these findings unveil a novel mechanism by which methylation of RelA dictates the turnover of NF-kappaB and controls the NF-kappaB-mediated inflammatory response. ..
  15. Jansson M, Durant S, Cho E, Sheahan S, Edelmann M, Kessler B, et al. Arginine methylation regulates the p53 response. Nat Cell Biol. 2008;10:1431-9 pubmed publisher
    ..Furthermore, PRMT5 depletion triggers p53-dependent apoptosis. Thus, methylation on arginine residues is an underlying mechanism of control during the p53 response. ..
  16. Wang L, Pal S, SIF S. Protein arginine methyltransferase 5 suppresses the transcription of the RB family of tumor suppressors in leukemia and lymphoma cells. Mol Cell Biol. 2008;28:6262-77 pubmed publisher
  17. Wysocki R, Javaheri A, Allard S, Sha F, Cote J, Kron S. Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol. 2005;25:8430-43 pubmed
    ..These results indicate a key role for chromatin and methylation of histone H3 Lys 79 in yeast DNA damage signaling. ..
  18. Tee W, Pardo M, Theunissen T, Yu L, Choudhary J, Hajkova P, et al. Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency. Genes Dev. 2010;24:2772-7 pubmed publisher
    ..Loss of Prmt5 or Mep50 results in derepression of differentiation genes, indicating the significance of the Prmt5/Mep50 complex for pluripotency, which may occur in conjunction with the leukemia inhibitory factor (LIF)/Stat3 pathway. ..
  19. Rank G, Cerruti L, Simpson R, Moritz R, Jane S, Zhao Q. Identification of a PRMT5-dependent repressor complex linked to silencing of human fetal globin gene expression. Blood. 2010;116:1585-92 pubmed publisher
    ..These studies define coordinated epigenetic events linked to fetal globin gene silencing, and provide potential therapeutic targets for the treatment of beta-thalassemia and SCD. ..
  20. Figaro S, Scrima N, Buckingham R, Heurgué Hamard V. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008;582:2352-6 pubmed publisher
    ..Here we show that the human proteins methylate human and yeast eRF1.eRF3.GTP in vitro, and that the MTase catalytic subunit can complement the growth defect of yeast strains deleted for mtq2. ..
  21. Hou Z, Peng H, Ayyanathan K, Yan K, Langer E, Longmore G, et al. The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression. Mol Cell Biol. 2008;28:3198-207 pubmed publisher
    ..Together, these data suggest that PRMT5 is an effector of SNAIL-dependent gene repression. ..
  22. du Chéné I, Basyuk E, Lin Y, Triboulet R, Knezevich A, Chable Bessia C, et al. Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 2007;26:424-35 pubmed
    ..Finally, we show in different cellular models, including PBMCs from HIV-1-infected donors, that HIV-1 reactivation could be achieved after HP1gamma RNA interference. ..
  23. Chen T, Muratore T, Schaner Tooley C, Shabanowitz J, Hunt D, Macara I. N-terminal alpha-methylation of RCC1 is necessary for stable chromatin association and normal mitosis. Nat Cell Biol. 2007;9:596-603 pubmed
    ..These data provide the first known function for N-terminal protein methylation. ..
  24. Mis J, Ner S, Grigliatti T. Identification of three histone methyltransferases in Drosophila: dG9a is a suppressor of PEV and is required for gene silencing. Mol Genet Genomics. 2006;275:513-26 pubmed
    ..The combined Su(var)3-9 and dG9a mutations have severe developmental defects suggesting an overlapping role for dG9a and Su(var)3-9 in the packaging of heterochromatin and gene silencing via a K9H3 methylation pathway. ..
  25. Seki Y, Yamaji M, Yabuta Y, Sano M, Shigeta M, Matsui Y, et al. Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice. Development. 2007;134:2627-38 pubmed
    ..We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs. ..
  26. Feldman N, Gerson A, Fang J, Li E, Zhang Y, Shinkai Y, et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat Cell Biol. 2006;8:188-94 pubmed
    ..Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 re-expression, thereby preventing reprogramming. ..
  27. Siomi M, Mannen T, Siomi H. How does the royal family of Tudor rule the PIWI-interacting RNA pathway?. Genes Dev. 2010;24:636-46 pubmed publisher
    ..Although Tud domains in Tud family members are known to be sDMA-binding modules, involvement of the Tudor family at the molecular level in the piRNA pathway has only recently come into focus. ..
  28. Dacwag C, Bedford M, SIF S, Imbalzano A. Distinct protein arginine methyltransferases promote ATP-dependent chromatin remodeling function at different stages of skeletal muscle differentiation. Mol Cell Biol. 2009;29:1909-21 pubmed publisher
    ..Thus, distinct arginine methyltransferases are employed at different times of skeletal muscle differentiation for the purpose of facilitating ATP-dependent chromatin-remodeling enzyme interaction and function at myogenic genes. ..
  29. Cesaro E, De Cegli R, Medugno L, Florio F, Grosso M, Lupo A, et al. The Kruppel-like zinc finger protein ZNF224 recruits the arginine methyltransferase PRMT5 on the transcriptional repressor complex of the aldolase A gene. J Biol Chem. 2009;284:32321-30 pubmed publisher
  30. Kirino Y, Vourekas A, Sayed N, de Lima Alves F, Thomson T, Lasko P, et al. Arginine methylation of Aubergine mediates Tudor binding and germ plasm localization. RNA. 2010;16:70-8 pubmed publisher
    ..Our study also suggests that the function of the piRNA pathway in PGC specification may be independent of its role in transposon control. ..
  31. Matsui T, Leung D, Miyashita H, Maksakova I, Miyachi H, Kimura H, et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature. 2010;464:927-31 pubmed publisher
    ..We propose that a DNA-methylation-independent pathway involving KAP1 and ESET/ESET-mediated H3K9me3 is required for proviral silencing during the period early in embryogenesis when DNA methylation is dynamically reprogrammed. ..
  32. Lacroix M, El Messaoudi S, Rodier G, Le Cam A, Sardet C, Fabbrizio E. The histone-binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5. EMBO Rep. 2008;9:452-8 pubmed publisher
    ..Moreover, both COPR5 depletion and overexpression affect CCNE1 promoter expression. We propose that COPR5 is an important chromatin adaptor for PRMT5 to function on a subset of its target genes. ..
  33. Gonsalvez G, Tian L, Ospina J, Boisvert F, Lamond A, Matera A. Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins. J Cell Biol. 2007;178:733-40 pubmed
    ..Furthermore, we show that the two enzymes function nonredundantly in Sm protein methylation. Lastly, we provide in vivo evidence demonstrating that Sm protein sDMA modification is required for snRNP biogenesis in human cells. ..
  34. Sripathy S, Stevens J, Schultz D. The KAP1 corepressor functions to coordinate the assembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRAB zinc finger protein-mediated transcriptional repression. Mol Cell Biol. 2006;26:8623-38 pubmed
  35. Davis C, Haberland M, Arnold M, Sutherland L, McDonald O, Richardson J, et al. PRISM/PRDM6, a transcriptional repressor that promotes the proliferative gene program in smooth muscle cells. Mol Cell Biol. 2006;26:2626-36 pubmed
    ..We conclude that PRISM acts as a novel epigenetic regulator of SMC phenotypic plasticity by suppressing differentiation and maintaining the proliferative potential of vascular SMCs. ..
  36. Furuno K, Masatsugu T, Sonoda M, Sasazuki T, Yamamoto K. Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro. Biochem Biophys Res Commun. 2006;345:1051-8 pubmed
    ..These results suggest that SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A. ..
  37. Zhao Q, Rank G, Tan Y, Li H, Moritz R, Simpson R, et al. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol. 2009;16:304-311 pubmed publisher
    ..Our findings define DNMT3A as both a reader and a writer of repressive epigenetic marks, thereby directly linking histone and DNA methylation in gene silencing. ..
  38. Ueda J, Tachibana M, Ikura T, Shinkai Y. Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP. J Biol Chem. 2006;281:20120-8 pubmed
    ..These data indicate that Wiz not only contributes to the stability of G9a but also links the G9a/GLP heteromeric complex to the CtBP co-repressor machinery. ..
  39. Smallwood A, Esteve P, Pradhan S, Carey M. Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 2007;21:1169-78 pubmed
    ..Additionally, silencing of the Survivin gene coincides with recruitment of G9a and HP1 in DNMT1 wild-type but not null cells. We conclude that direct interactions between HP1 and DNMT1 mediate silencing of euchromatic genes. ..
  40. Dacwag C, Ohkawa Y, Pal S, SIF S, Imbalzano A. The protein arginine methyltransferase Prmt5 is required for myogenesis because it facilitates ATP-dependent chromatin remodeling. Mol Cell Biol. 2007;27:384-94 pubmed
    ..We therefore conclude that a histone modifying enzyme is necessary to permit an ATP-dependent chromatin remodeling enzyme to function. ..
  41. Hayashi K, Matsui Y. Meisetz, a novel histone tri-methyltransferase, regulates meiosis-specific epigenesis. Cell Cycle. 2006;5:615-20 pubmed
    ..This article reviews the function of Meisetz and prospects the epigenetic background allowing proper progression of meiosis in mouse germ cells. ..
  42. Tae S, Karkhanis V, Velasco K, Yaneva M, Erdjument Bromage H, Tempst P, et al. Bromodomain protein 7 interacts with PRMT5 and PRC2, and is involved in transcriptional repression of their target genes. Nucleic Acids Res. 2011;39:5424-38 pubmed publisher
    ..These findings highlight the role played by BRD7 in PRMT5- and PRC2-induced transcriptional silencing, and indicate that recruitment of specific RDMs and KDMs is required for efficient transcriptional derepression. ..
  43. Bilodeau S, Kagey M, Frampton G, Rahl P, Young R. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev. 2009;23:2484-9 pubmed publisher
    ..These genes are subjected to repression by both Polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state. ..
  44. Vagin V, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, et al. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev. 2009;23:1749-62 pubmed publisher
  45. Dirk L, Flynn E, Dietzel K, Couture J, Trievel R, Houtz R. Kinetic manifestation of processivity during multiple methylations catalyzed by SET domain protein methyltransferases. Biochemistry. 2007;46:3905-15 pubmed
  46. Lohmann F, Loureiro J, Su H, Fang Q, Lei H, Lewis T, et al. KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation. Stem Cells. 2010;28:201-12 pubmed publisher
    ..Our studies thus demonstrate an essential role for KMT1E in the control of developmentally regulated gene expression programs in ES cells. ..
  47. Andreu Pérez P, Esteve Puig R, de Torre Minguela C, López Fauqued M, Bech Serra J, Tenbaum S, et al. Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF. Sci Signal. 2011;4:ra58 pubmed publisher
    ..This additional level of regulation within the RAS pathway may lead to the identification of new targets for therapeutic intervention. ..
  48. Li Y, Reddy M, Miao F, Shanmugam N, Yee J, Hawkins D, et al. Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation. J Biol Chem. 2008;283:26771-81 pubmed publisher
    ..These results demonstrate a novel role for SET7/9 in inflammation and diabetes. ..
  49. Sampath S, Marazzi I, Yap K, Sampath S, Krutchinsky A, Mecklenbrauker I, et al. Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell. 2007;27:596-608 pubmed
  50. Le Guezennec X, Vermeulen M, Brinkman A, Hoeijmakers W, Cohen A, Lasonder E, et al. MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol. 2006;26:843-51 pubmed
    ..Our data show that MBD2/NuRD and MBD3/NuRD are distinct protein complexes with different biochemical and functional properties. ..
  51. Levy D, Kuo A, Chang Y, Schaefer U, Kitson C, Cheung P, et al. Lysine methylation of the NF-?B subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-?B signaling. Nat Immunol. 2011;12:29-36 pubmed publisher
    ..Our findings establish a previously uncharacterized mechanism by which chromatin signaling regulates inflammation programs. ..
  52. Schotta G, Sengupta R, Kubicek S, Malin S, Kauer M, Callen E, et al. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev. 2008;22:2048-61 pubmed publisher
    ..Thus, conversion to an H4K20me1 state results in compromised chromatin that is insufficient to protect genome integrity and to process a DNA-rearranging differentiation program in the mouse. ..
  53. Nishida K, Okada T, Kawamura T, Mituyama T, Kawamura Y, Inagaki S, et al. Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines. EMBO J. 2009;28:3820-31 pubmed publisher
    ..Thus, in germline cells, piRNAs are quality-controlled by dPRMT5 that modifies PIWI proteins, in tight association with Tud. ..