May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2. (6S)-5,6,7,8-tetrahydrofolate + ATP + formate = (6S)-10-formyltetrahydrofolate + ADP + phosphate One-carbon metabolism; tetrahydrofolate interconversion. Homodimer. Detected in most tissues, highest expression found in placenta, thymus and brain. Low expression is found in liver and skeletal muscle. Up-regulated in colon adenocarcinoma. This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain. May participate in the progression of colorectal cancer by conferring growth advantage. Could be a new molecular target for cancer therapy. In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family. In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family. Was originally thought to be a trifunctional enzyme but only a formyltetrahydrofolate synthetase activity was detected and not a dehydrogenase/cyclohydrogenase activity.