In eukaryotes, the enzyme occurs as a trifunctional enzyme that also has methylenetetrahydrofolate dehydrogenase (NADP+) (EC
1.5.1.5) and formate---tetrahydrofolate ligase (EC
6.3.4.3) activity. In some prokaryotes, it occurs as a bifunctional enzyme that also has dehydrogenase (EC
1.5.1.5) activity or formimidoyltetrahydrofolate cyclodeaminase (EC
4.3.1.4) activity.