PROSITE documentation PDOC51143

MT-A70-like family profile

N6-methyladenosine (m6A) is present at internal sites in eukaryotic mRNA. It is present only within a defined sequence context that has been shown to be conserved across species from plants to man. Despite its ubiquity and conserved sequence specificity, the functional significance of this modification remains a mystery [1,2].

MT-A70 is the S-adenosylmethionine-binding subunit of human mRNA [N6-adenosine]-methyltransferase (MTase), an enzyme that sequence-specifically methylates adenines in pre-mRNAs. Proteins with sequence similarity to MT-A70 have been identified in eukaryotes and prokaryotes. The resulting family is defined by sequence similarity in the carboxyl-proximal regions of the respective proteins. The amino-proximal regions of the eukaryotic proteins are highly diverse, often Pro-rich, and are conserved only within individual subfamilies [2]. Corresponding regions are not present in prokaryotic members of the family. MT-A70-like proteins contain examples of some of the consensus methyltransferase motifs that have been derived from mutational and structural studies of bacterial DNA methyltransferases, including the universally conserved motif IV catalytic residues and a proposed motif I (AdoMet binding) element [1]. The MT-A70-like family comprises four subfamilies with varying degrees of interrelatedness. One subfamily is a small group of bacterial DNA: m6A MTases. The other three are paralogous eukaryotic lineages, two of which have not been associated with MTase activity but include proteins that regulate mRNA levels via unknown mechanisms apparently not involving methylation [1].

Some proteins known to belong to the MT-A70-like family are listed below:

• Human N6-adenosine-methyltransferase 70 kDa subunit (MT-A70) (EC 2.1.1.62).
• Yeast N6-adenosine-methyltransferase IME4 (EC 2.1.1.62), which is important for induction of sporulation.
• Yeast karyogamy protein KAR4, a phosphoprotein required for expression of karyogamy-specific genes during mating. It also acts during mitosis and meiosis. It has been suggested that KAR4 is inactive for methyltransfer and may not even bind AdoMet.