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   03-AUG-2022, entry version 75.
DE   RecName: Full=5,10-methylenetetrahydrofolate reductase;
DE            EC=1.5.1.20;
GN   Name=metF;
OS   Streptomyces lividans.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=1916;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6S)-5-methyl-5,6,7,8-tetrahydrofolate + NADP(+) = (6R)-5,10-
CC         methylene-5,6,7,8-tetrahydrofolate + H(+) + NADPH;
CC         Xref=Rhea:RHEA:19817, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC         ChEBI:CHEBI:18608, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.5.1.20;
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=1.5.1.20;
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC   -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; AJ001630; CAA04885.1; -; Genomic_DNA.
DR   AlphaFoldDB; O54235; -.
DR   SMR; O54235; -.
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:0106313; F:methylenetetrahydrofolate reductase NADPH 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   InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR   InterPro; IPR003171; Mehydrof_redctse-like.
DR   InterPro; IPR004620; MTHF_reductase_bac.
DR   Pfam; PF02219; MTHFR; 1.
DR   SUPFAM; SSF51730; SSF51730; 1.
DR   TIGRFAMs; TIGR00676; fadh2; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis; FAD; Flavoprotein; Methionine biosynthesis; NAD;
KW   NADP; 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"
FT   BINDING         30..35
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         61..64
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         61..62
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         90
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         120..122
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         122
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         140..141
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         165..168
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         174..181
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         192
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
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