ID METF_SALTY Reviewed; 296 AA. AC P11003; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 27-MAR-2024, entry version 142. DE RecName: Full=5,10-methylenetetrahydrofolate reductase; DE EC=1.5.1.54 {ECO:0000250|UniProtKB:P0AEZ1}; GN Name=metF; OrderedLocusNames=STM4105; OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Salmonella. OX NCBI_TaxID=99287; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=LT2; RX PubMed=2841568; DOI=10.1007/bf00334692; RA Stauffer G.V., Stauffer L.T.; RT "Cloning and nucleotide sequence of the Salmonella typhimurium LT2 metF RT gene and its homology with the corresponding sequence of Escherichia RT coli."; RL Mol. Gen. Genet. 212:246-251(1988). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=LT2 / SGSC1412 / ATCC 700720; RX PubMed=11677609; DOI=10.1038/35101614; RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P., RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D., RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E., RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R., RA Wilson R.K.; RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2."; RL Nature 413:852-856(2001). CC -!- FUNCTION: Catalyzes the NADH-dependent reduction of 5,10- CC methylenetetrahydrofolate to 5-methyltetrahydrofolate. Is required to CC provide the methyl group necessary for methionine synthetase to convert CC homocysteine to methionine; the methyl group is given by 5- CC methyltetrahydrofolate. {ECO:0000250|UniProtKB:P0AEZ1}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NAD(+) = (6R)-5,10- CC methylene-5,6,7,8-tetrahydrofolate + H(+) + NADH; CC Xref=Rhea:RHEA:19821, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636, CC ChEBI:CHEBI:18608, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.5.1.54; CC Evidence={ECO:0000250|UniProtKB:P0AEZ1}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19823; CC Evidence={ECO:0000250|UniProtKB:P0AEZ1}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:P0AEZ1}; CC -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion. CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo CC pathway. {ECO:0000250|UniProtKB:P0AEZ1}. CC -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07689; CAA30531.1; -; Genomic_DNA. DR EMBL; AE006468; AAL22945.1; -; Genomic_DNA. DR PIR; S03169; S03169. DR RefSeq; NP_462986.1; NC_003197.2. DR RefSeq; WP_000007508.1; NC_003197.2. DR AlphaFoldDB; P11003; -. DR SMR; P11003; -. DR STRING; 99287.STM4105; -. DR PaxDb; 99287-STM4105; -. DR GeneID; 1255632; -. DR KEGG; stm:STM4105; -. DR PATRIC; fig|99287.12.peg.4328; -. DR HOGENOM; CLU_025841_0_0_6; -. DR OMA; EMHPQAR; -. DR PhylomeDB; P11003; -. DR BioCyc; SENT99287:STM4105-MONOMER; -. DR UniPathway; UPA00051; -. DR UniPathway; UPA00193; -. DR Proteomes; UP000001014; Chromosome. DR GO; GO:0005829; C:cytosol; IEA:InterPro. DR GO; GO:0071949; F:FAD binding; IBA:GO_Central. DR GO; GO:0004489; F:methylenetetrahydrofolate reductase (NAD(P)H) activity; IBA:GO_Central. DR GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA. DR GO; GO:0009086; P:methionine biosynthetic process; IBA:GO_Central. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IBA:GO_Central. DR CDD; cd00537; MTHFR; 1. DR Gene3D; 3.20.20.220; -; 1. DR InterPro; IPR029041; FAD-linked_oxidoreductase-like. DR InterPro; IPR003171; Mehydrof_redctse-like. DR InterPro; IPR004620; MTHF_reductase_bac. DR NCBIfam; TIGR00676; fadh2; 1. DR PANTHER; PTHR45754; METHYLENETETRAHYDROFOLATE REDUCTASE; 1. DR PANTHER; PTHR45754:SF3; METHYLENETETRAHYDROFOLATE REDUCTASE; 1. DR Pfam; PF02219; MTHFR; 1. DR SUPFAM; SSF51730; FAD-linked oxidoreductase; 1. PE 3: Inferred from homology; KW Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD; KW Oxidoreductase; Reference proteome. FT CHAIN 1..296 FT /note="5,10-methylenetetrahydrofolate reductase" FT /id="PRO_0000190264" FT ACT_SITE 28 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 59 FT /ligand="NADH" FT /ligand_id="ChEBI:CHEBI:57945" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 60 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 62 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 88 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 118 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 119 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 120 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 120 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 132 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 152 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 156 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 159 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 165 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 168 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 171 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 172 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 183 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 183 FT /ligand="NADH" FT /ligand_id="ChEBI:CHEBI:57945" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 219 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 279 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT CONFLICT 94 FT /note="A -> P (in Ref. 1; CAA30531)" FT /evidence="ECO:0000305" SQ SEQUENCE 296 AA; 33173 MW; 2B834F880B56A643 CRC64; MSFFHANQRE ALNQSLAEVQ GQINVSFEFF PPRTSEMEQT LWNSIDRLSS LKPKFVSVTY GANSGERDRT HSVIKGIKER TGLEAAPHLT CIDATRDELR TIARDYWNNG IRHIVALRGD LPPGSGKPEM YAADLVGLLK EVADFDISVA AYPEVHPEAK SAQADLLNLK RKVDAGANRA ITQFFFDVES YLRFRDRCVS AGIDVEIIPG ILPVSNFKQA KKFADMTNVR IPSWMSLMFE GLDNDAETRK LVGANIAMDM VKILSREGVK DFHFYTLNRA EMSYAICHTL GVRPGL //