UniProt functional annotation for P0A884

UniProt code: P0A884.

Organism: Escherichia coli (strain K12).
Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.
 
Function: Catalyzes the reductive methylation of 2'-deoxyuridine-5'- monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and reductant in the reaction, yielding dihydrofolate (DHF) as a by-product (PubMed:3286637, PubMed:2223754, PubMed:9826509). This enzymatic reaction provides an intracellular de novo source of dTMP, an essential precursor for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation (PubMed:7708505). {ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, ECO:0000269|PubMed:7708505, ECO:0000269|PubMed:9826509}.
 
Catalytic activity: Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8- dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636, ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422; EC=2.1.1.45; Evidence={ECO:0000255|HAMAP-Rule:MF_00008, ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:3286637, ECO:0000269|PubMed:9826509};
Biophysicochemical properties: Kinetic parameters: KM=50 uM for dUMP {ECO:0000269|PubMed:3286637}; KM=25 uM for 5,10-methylenetetrahydrofolate {ECO:0000269|PubMed:3286637}; KM=4.1 uM for dUMP {ECO:0000269|PubMed:9826509}; KM=13.6 uM for 5,10-methylenetetrahydrofolate {ECO:0000269|PubMed:9826509}; Vmax=5.47 umol/min/mg enzyme {ECO:0000269|PubMed:3286637}; Note=kcat is 8.8 sec(-1). {ECO:0000269|PubMed:9826509};
Pathway: Pyrimidine metabolism; dTTP biosynthesis. {ECO:0000255|HAMAP- Rule:MF_00008}.
Subunit: Homodimer. {ECO:0000269|PubMed:2223754, ECO:0000269|PubMed:8973201}.
Subcellular location: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00008}.
Ptm: Although not discussed in the published references, Met-1 is represented in the submitted PDB entries as being modified by either a formyl, or a carboxyl group. The N-terminal is probably N- (dihydroxymethyl)methionine, the hydrated form of N-formylmethionine.
Similarity: Belongs to the thymidylate synthase family. Bacterial-type ThyA subfamily. {ECO:0000255|HAMAP-Rule:MF_00008}.

Annotations taken from UniProtKB at the EBI.