Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13

Abstract

METTL13 (also known as eEF1A-KNMT and FEAT) is a dual methyltransferase reported to target the N-terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13-mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of global protein synthesis and translation of specific codons. Aberrant regulation of METTL13 has been linked to several types of cancer but the precise mechanisms are not yet fully understood. In this article, the current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context. The links between METTL13 and diseases, mainly different types of cancer, are also summarized. Finally, key challenges and opportunities for METTL13 research are pinpointed in a prospective outlook.

Human seven-β-strand (METTL) methyltransferases - conquering the universe of protein lysine methylation

“…There has been tremendous progress on identifying novel human 7BS KMTs during the last decade, and 16 such enzymes have now been characterized. We will keep the descriptions of the individual KMTs rather short, as several of them have already been covered by various review articles ( 23 , 45 , 46 , 47 ). Interestingly, certain groups of proteins are overrepresented among the human 7BS KMT substrates, i.e.…”

Methyltransferase-like proteins in cancer biology and potential therapeutic targeting

“…METTL11A is significantly overexpressed in cervical cancer and m6A modification of ELK3 mRNA promotes cervical cancer cell metastasis [ 8 ]. METTL13 is involved in eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) modification, increasing GTPase activity, protein translation, synthesis of proteins associated with oncogenic growth signals in the presence of KRAS [ 113 , 114 ] and promoting tumorigenesis in vivo. METTL13 and eEF1AK55me2 levels are upregulated in cancers and negatively associated with survival in pancreatic and lung cancer patients [ 115 ].…”

Unlocking the mysteries of alpha-N-terminal methylation and its diverse regulatory functions

“…eEF1α delivers aminoacyl-tRNAs to the A-site of a ribosome powered by GTP during the translational process and is subject to extensive methylation by multiple MTases. EF1A-KNMTs exhibit dual N-terminal MTase and lysine MTase activities ( 46 ). The human enzyme, METTL13, modifies the G1 of eEF1α via the C-terminal orphan MTase (denoted as MT13-C) ( Fig.…”