ID METF_STRLI Reviewed; 307 AA. AC O54235; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 13-SEP-2023, entry version 80. DE RecName: Full=5,10-methylenetetrahydrofolate reductase {ECO:0000303|PubMed:9515933}; DE EC=1.5.1.54 {ECO:0000250|UniProtKB:P0AEZ1}; GN Name=metF {ECO:0000303|PubMed:9515933}; OS Streptomyces lividans. OC Bacteria; Actinomycetota; Actinomycetes; Kitasatosporales; OC Streptomycetaceae; Streptomyces. OX NCBI_TaxID=1916; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN METHIONINE BIOSYNTHESIS, RP DISRUPTION PHENOTYPE, AND PATHWAY. RC STRAIN=66 / 1326; RX PubMed=9515933; DOI=10.1128/jb.180.6.1586-1591.1998; RA Blanco J., Coque J.R., Martin J.; RT "The folate branch of the methionine biosynthesis pathway in Streptomyces RT lividans: disruption of the 5,10-methylenetetrahydrofolate reductase gene RT leads to methionine auxotrophy."; RL J. Bacteriol. 180:1586-1591(1998). 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:0000269|PubMed:9515933}. CC -!- DISRUPTION PHENOTYPE: Disruption of the metF gene leads to methionine CC auxotrophy. {ECO:0000269|PubMed:9515933}. 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; AJ001630; CAA04885.1; -; Genomic_DNA. DR AlphaFoldDB; O54235; -. DR SMR; O54235; -. DR UniPathway; UPA00051; -. DR UniPathway; UPA00193; -. DR GO; GO:0005829; C:cytosol; IEA:InterPro. DR GO; GO:0106312; F:methylenetetrahydrofolate reductase NADH activity; IEA:RHEA. DR GO; GO:0009086; P:methionine biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0035999; P:tetrahydrofolate interconversion; IEA:UniProtKB-UniPathway. 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 1: Evidence at protein level; KW Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD; KW Oxidoreductase. FT CHAIN 1..307 FT /note="5,10-methylenetetrahydrofolate reductase" FT /id="PRO_0000190266" FT ACT_SITE 30 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 61 FT /ligand="NADH" FT /ligand_id="ChEBI:CHEBI:57945" 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 64 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 90 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" 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 121 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 122 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 122 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 141 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 174 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 177 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 181 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 192 FT /ligand="(6S)-5-methyl-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:18608" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" FT BINDING 192 FT /ligand="NADH" FT /ligand_id="ChEBI:CHEBI:57945" FT /evidence="ECO:0000250|UniProtKB:P0AEZ1" SQ SEQUENCE 307 AA; 33268 MW; 0CA09C336036D8A9 CRC64; MALGTASTRT DRARTVRDIL ATGKTTYSFE FSAPKTPKGE KNLWSALRRV EAVAPDFVSV TYGAGGSTRA GTVRETQQIV ADTTLTPVAH LTAVDHSVAE LRNIIGQYAD AGIRNMLAVR GDPPGDPNAD WIAHPEGLTY AAELVRLIKE SGDFCVGVAA FPEMHPRSAD WDTDVTNFVD KCRAGADYAI TQMFFQPDSY LRLRDRVAAA GCATPVIPEV MPVTSVKMLE RLPKLSNASF PAELKERILT AKDDPAAVRS IGIEFATEFC ARLLAEGVPG LHFITLNNST ATLEIYENLG LHHPPRA //