Fig. 1

Domain architecture of methyltransferase families. a The de novo DNA methyltransferases, DNMT3A, DNMT3B, and DNMT3L all share a similar ADD (Atrx-Dnmt3-Dnmt3l) domain. DNMT3A and DNMT3B share a PWWP (Pro-Trp-Trp-Pro) domain and a conserved catalytic methyltransferase (MTase) domain. DNMT3L possesses an inactive MTase domain variant, shown in a lighter color and italicized to distinguish it from the active MTase domains. b The PRMT family consists of 9 enzymes containing a conserved catalytic MTase core. Several notable features are found at the N-termini of some PRMTs: PRMT2 contains an SH3 domain, PRMT3 contains a zinc finger domain (ZFD), PRMT5 contains a TIM barrel, PRMT8 is N-terminally myristoylated, and PRMT9 contains three TRP (tetratricopeptide) motifs. PRMT7 and PRMT9 contain two tandem MTase domains, with the C-terminal MTase domains lacking some of the conserved motifs of the canonical PRMT core rendering them catalytically inactive. The inactive MTase domains are italicized and shown in a lighter color than the active. Type I PRMTs also have a conserved dimerization arm shown with dashed lines within the MTase domains. c The METTL family members discussed here include the RNA (m6A) methyltransferases METTL3 and METTL14, and the N-terminal methyltransferases METTL11A, METTL11B, and METTL13. The m6A methyltransferase METTL3 contains two nuclear localization signals (NLS), and a ZFD at its N-terminus, while METTL14 possesses a catalytically inactive MTase domain (italicized and shown in a lighter color than the active MTase domain) and RGG repeats (RGG) at its C-terminus. The N-terminal methyltransferases METTL11A and METTL11B each only contain one active MTase domain, while METTL13 contains two active MTase domains with distinct functions. Created with Biorender.com