Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme

We report the nucleotide sequence of a cloned cDNA, pMTS-3, that contains a1-kb insert corresponding to mouse thymidylate synthase (E.C. 2.1.1.45).The open reading frame of 921 nucleotides from the first AUG to thetermination codon specifies a protein with a molecular mass of 34,962daltons. The predicted amino acid sequence is 90% identical with that ofthe human enzyme. The mouse sequence also has an extremely high degree ofsimilarity (as much as 55% identity) with prokaryotic thymidylate synthasesequences, indicating that thymidylate synthase is among the most highlyconserved proteins studied to date. The similarity is especially pronounced(as much as 80% identity) in the 44-amino-acid region encompassing thebinding site for deoxyuridylic acid. The cDNA sequence also suggests thatmouse thymidylate synthase mRNA lacks a 3' untranslated region, since thetermination codon, UAA, is followed immediately by a poly(A) segment.