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- Chromatin modifying enzymes
- 2.1.1.43 Histone methyltransferases (HMTs)
2.1.1.43 Histone methyltransferases (HMTs)
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Enzymes
3313
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ASH1 like histone lysine methyltransferase Show summary »« Hide summary
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DOT1 like histone lysine methyltransferase
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euchromatic histone lysine methyltransferase 1 Show summary »« Hide summary
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euchromatic histone lysine methyltransferase 2 Show summary »« Hide summary
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EZH1 (enhancer of zeste 1 polycomb repressive complex 2 subunit)
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EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit)
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lysine methyltransferase 2B Show summary »« Hide summary
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lysine methyltransferase 2A Show summary »« Hide summary
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lysine methyltransferase 2C Show summary »« Hide summary
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lysine methyltransferase 2D Show summary »« Hide summary
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lysine methyltransferase 2E (inactive) Show summary »« Hide summary
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lysine methyltransferase 5A Show summary »« Hide summary
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lysine methyltransferase 5B Show summary »« Hide summary
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lysine methyltransferase 5C Show summary »« Hide summary
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nuclear receptor binding SET domain protein 1 Show summary »« Hide summary
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nuclear receptor binding SET domain protein 2 Show summary »« Hide summary
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PR/SET domain 2 Show summary »« Hide summary
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SET domain containing 1A, histone lysine methyltransferase Show summary »« Hide summary
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SET domain containing 1B, histone lysine methyltransferase Show summary »« Hide summary
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SET domain containing 2, histone lysine methyltransferase Show summary »« Hide summary
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SET domain containing 7, histone lysine methyltransferase
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SET domain bifurcated histone lysine methyltransferase 1 Show summary »« Hide summary
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SET domain bifurcated histone lysine methyltransferase 2 Show summary »« Hide summary
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SET and MYND domain containing 2
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SET and MYND domain containing 3 Show summary »« Hide summary
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SUV39H1 histone lysine methyltransferase Show summary »« Hide summary
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SUV39H2 histone lysine methyltransferase Show summary »« Hide summary
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References
1. Albert M, Helin K. (2010) Histone methyltransferases in cancer. Semin Cell Dev Biol, 21 (2): 209-20. [PMID:19892027]
2. Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA et al.. (2014) (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci USA, 111 (35): 12853-8. [PMID:25136132]
3. Blum G, Ibáñez G, Rao X, Shum D, Radu C, Djaballah H, Rice JC, Luo M. (2014) Small-molecule inhibitors of SETD8 with cellular activity. ACS Chem Biol, 9 (11): 2471-8. [PMID:25137013]
4. Bödör C, Grossmann V, Popov N, Okosun J, O'Riain C, Tan K, Marzec J, Araf S, Wang J, Lee AM et al.. (2013) EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood, 122 (18): 3165-8. [PMID:24052547]
5. Campbell JE, Kuntz KW, Knutson SK, Warholic NM, Keilhack H, Wigle TJ, Raimondi A, Klaus CR, Rioux N, Yokoi A et al.. (2015) EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity. ACS Med Chem Lett, 6 (5): 491-5. [PMID:26005520]
6. Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y. (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science, 298 (5595): 1039-43. [PMID:12351676]
7. Cherblanc FL, Chapman KL, Brown R, Fuchter MJ. (2013) Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases. Nat Chem Biol, 9 (3): 136-7. [PMID:23416387]
8. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP et al.. (2013) Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood, 122 (6): 1017-25. [PMID:23801631]
9. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnston LD, Scott MP, Smith JJ, Xiao Y et al.. (2011) Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell, 20 (1): 53-65. [PMID:21741596]
10. Diaz E, Machutta CA, Chen S, Jiang Y, Nixon C, Hofmann G, Key D, Sweitzer S, Patel M, Wu Z et al.. (2012) Development and validation of reagents and assays for EZH2 peptide and nucleosome high-throughput screens. J Biomol Screen, 17 (10): 1279-92. [PMID:22904200]
11. Greiner D, Bonaldi T, Eskeland R, Roemer E, Imhof A. (2005) Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat Chem Biol, 1 (3): 143-5. [PMID:16408017]
12. Knutson SK, Warholic NM, Wigle TJ, Klaus CR, Allain CJ, Raimondi A, Porter Scott M, Chesworth R, Moyer MP, Copeland RA et al.. (2013) Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci USA, 110 (19): 7922-7. [PMID:23620515]
13. Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR, Sacks JD, Raimondi A, Majer CR, Song J et al.. (2012) A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol, 8 (11): 890-6. [PMID:23023262]
14. Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E et al.. (2013) An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem Biol, 8 (6): 1324-34. [PMID:23614352]
15. Krivega I, Byrnes C, de Vasconcellos JF, Lee YT, Kaushal M, Dean A, Miller JL. (2015) Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/γ-globin looping. Blood, 126 (5): 665-72. [PMID:25979948]
16. Kubicek S, O'Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML, Rea S, Mechtler K, Kowalski JA, Homon CA et al.. (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell, 25 (3): 473-81. [PMID:17289593]
17. Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D. (2002) Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev, 16 (22): 2893-905. [PMID:12435631]
18. Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV et al.. (2013) Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem, 56 (21): 8931-42. [PMID:24102134]
19. Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G, Chau I, Siarheyeva A et al.. (2010) Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. J Med Chem, 53 (15): 5844-57. [PMID:20614940]
20. Liu L, Parolia A, Liu Y, Hou C, He T, Qiao Y, Eyunni S, Luo J, Li C, Wang Y et al.. (2024) Discovery of LLC0424 as a Potent and Selective in Vivo NSD2 PROTAC Degrader. J Med Chem, 67 (9): 6938-6951. [PMID:38687638]
21. Margueron R, Li G, Sarma K, Blais A, Zavadil J, Woodcock CL, Dynlacht BD, Reinberg D. (2008) Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol Cell, 32 (4): 503-18. [PMID:19026781]
22. Margueron R, Reinberg D. (2011) The Polycomb complex PRC2 and its mark in life. Nature, 469 (7330): 343-9. [PMID:21248841]
23. Martin C, Zhang Y. (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol, 6 (11): 838-49. [PMID:16261189]
24. Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, Van Aller GS, Huddleston M, Dhanak D et al.. (2014) SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature, 510 (7504): 283-7. [PMID:24847881]
25. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, Liu Y, Graves AP, Della Pietra 3rd A, Diaz E et al.. (2012) EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 492 (7427): 108-12. [PMID:23051747]
26. Mitchell LH, Boriack-Sjodin PA, Smith S, Thomenius M, Rioux N, Munchhof M, Mills JE, Klaus C, Totman J, Riera TV et al.. (2016) Novel Oxindole Sulfonamides and Sulfamides: EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor. ACS Med Chem Lett, 7 (2): 134-8. [PMID:26985287]
27. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, Paul JE, Boyle M, Woolcock BW, Kuchenbauer F et al.. (2010) Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet, 42 (2): 181-5. [PMID:20081860]
28. Murase T, Ri M, Narita T, Fujii K, Masaki A, Iida S, Inagaki H. (2019) Immunohistochemistry for identification of CCND1, NSD2, and MAF gene rearrangements in plasma cell myeloma. Cancer Sci, 110 (8): 2600-2606. [PMID:31218784]
29. Parenti MD, Naldi M, Manoni E, Fabini E, Cederfelt D, Talibov VO, Gressani V, Guven U, Grossi V, Fasano C et al.. (2022) Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3. Eur J Med Chem, 243: 114683. [PMID:36116234]
30. Qi W, Chan H, Teng L, Li L, Chuai S, Zhang R, Zeng J, Li M, Fan H, Lin Y et al.. (2012) Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci USA, 109 (52): 21360-5. [PMID:23236167]
31. Renneville A, Van Galen P, Canver MC, McConkey M, Krill-Burger JM, Dorfman DM, Holson EB, Bernstein BE, Orkin SH, Bauer DE et al.. (2015) EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression. Blood, 126 (16): 1930-9. [PMID:26320100]
32. Rosano D, Sofyali E, Dhilman H, Ghirardi C, Ivanoiu D, Heide T, Vingaini A, Bertolotti A, Pruneri G, Canale E et al.. (2024) Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells. Cancer Discovery, 14 (1): 1-24. DOI: 10.1158/2159-8290.CD-23-1161
33. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, Ugarte A, Roa S, Paiva B, Estella-Hermoso de Mendoza A et al.. (2017) Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies. Nat Commun, 8: 15424. [PMID:28548080]
34. SGC. A-196 A selective chemical probe for SUV420H1/H2. Accessed on 11/12/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/A-196
35. SGC. A-366: a chemical Probe for G9a/GLP. Accessed on 03/03/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/A-366
36. SGC. BAY-6035 A potent, peptide-competitive chemical probe for SMYD3. Accessed on 26/06/2025. Modified on 26/06/2025. thesgc.org, https://www.thesgc.org/chemical-probes/bay-6035
37. SGC. LLY-507: A chemical probe for SMYD2 protein lysine methyltransferase. Accessed on 03/03/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/LLY-507
38. Shen X, Liu Y, Hsu YJ, Fujiwara Y, Kim J, Mao X, Yuan GC, Orkin SH. (2008) EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol Cell, 32 (4): 491-502. [PMID:19026780]
39. Shiogama S, Yoshiba S, Soga D, Motohashi H, Shintani S. (2013) Aberrant expression of EZH2 is associated with pathological findings and P53 alteration. Anticancer Res, 33 (10): 4309-17. [PMID:24122997]
40. Sneeringer CJ, Scott MP, Kuntz KW, Knutson SK, Pollock RM, Richon VM, Copeland RA. (2010) Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci USA, 107 (49): 20980-5. [PMID:21078963]
41. Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C, Vedadi M et al.. (2014) Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med Chem Lett, 5 (2): 205-9. [PMID:24900801]
42. Tang H, Yu A, Xing L, Chen X, Ding H, Yang H, Song Z, Shi Q, Geng M, Huang X et al.. (2023) Structural Modification and Pharmacological Evaluation of Substituted Quinoline-5,8-diones as Potent NSD2 Inhibitors. J Med Chem, 66 (2): 1634-1651. [PMID:36642961]
43. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A et al.. (2011) A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol, 7 (8): 566-74. [PMID:21743462]
44. Velez J, Han Y, Yim H, Yang P, Deng Z, Park KS, Kabir M, Kaniskan HÜ, Xiong Y, Jin J. (2024) Discovery of the First-in-class G9a/GLP PROTAC Degrader. bioRxiv, [Preprint]. [PMID:38464025]
45. Verma SK, Tian X, LaFrance LV, Duquenne C, Suarez DP, Newlander KA, Romeril SP, Burgess JL, Grant SW, Brackley JA et al.. (2012) Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett, 3 (12): 1091-6. [PMID:24900432]
46. Williams DE, Dalisay DS, Li F, Amphlett J, Maneerat W, Chavez MA, Wang YA, Matainaho T, Yu W, Brown PJ et al.. (2013) Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8. Org Lett, 15 (2): 414-7. [PMID:23272941]
47. Yoshioka Y, Suzuki T, Matsuo Y, Nakakido M, Tsurita G, Simone C, Watanabe T, Dohmae N, Nakamura Y, Hamamoto R. (2016) SMYD3-mediated lysine methylation in the PH domain is critical for activation of AKT1. Oncotarget, 7 (46): 75023-75037. [PMID:27626683]
48. Yoshioka Y, Suzuki T, Matsuo Y, Tsurita G, Watanabe T, Dohmae N, Nakamura Y, Hamamoto R. (2017) Protein lysine methyltransferase SMYD3 is involved in tumorigenesis through regulation of HER2 homodimerization. Cancer Med, 6 (7): 1665-1672. [PMID:28639750]
49. Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J et al.. (2012) Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun, 3: 1288. [PMID:23250418]
50. Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH et al.. (2013) Bromo-deaza-SAH: a potent and selective DOT1L inhibitor. Bioorg Med Chem, 21 (7): 1787-94. [PMID:23433670]
51. Yuan Y, Wang Q, Paulk J, Kubicek S, Kemp MM, Adams DJ, Shamji AF, Wagner BK, Schreiber SL. (2012) A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem Biol, 7 (7): 1152-7. [PMID:22536950]
How to cite this family page
Database page citation:
2.1.1.43 Histone methyltransferases (HMTs). Accessed on 10/09/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=871.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.
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