ID   METF_BUCAP              Reviewed;         292 AA.
AC   Q8KA62;
DT   08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 102.
DE   RecName: Full=5,10-methylenetetrahydrofolate reductase;
DE            EC=1.5.1.20;
GN   Name=metF; OrderedLocusNames=BUsg_043;
OS   Buchnera aphidicola subsp. Schizaphis graminum (strain Sg).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC   Erwiniaceae; Buchnera.
OX   NCBI_TaxID=198804;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Sg;
RX   PubMed=12089438; DOI=10.1126/science.1071278;
RA   Tamas I., Klasson L., Canbaeck B., Naeslund A.K., Eriksson A.-S.,
RA   Wernegreen J.J., Sandstroem J.P., Moran N.A., Andersson S.G.E.;
RT   "50 million years of genomic stasis in endosymbiotic bacteria.";
RL   Science 296:2376-2379(2002).
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; AE013218; AAM67614.1; -; Genomic_DNA.
DR   RefSeq; WP_011053580.1; NC_004061.1.
DR   AlphaFoldDB; Q8KA62; -.
DR   SMR; Q8KA62; -.
DR   STRING; 198804.BUsg_043; -.
DR   EnsemblBacteria; AAM67614; AAM67614; BUsg_043.
DR   KEGG; bas:BUsg_043; -.
DR   eggNOG; COG0685; Bacteria.
DR   HOGENOM; CLU_025841_0_0_6; -.
DR   OMA; EMHPQAR; -.
DR   OrthoDB; 1425269at2; -.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000000416; Chromosome.
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..292
FT                   /note="5,10-methylenetetrahydrofolate reductase"
FT                   /id="PRO_0000190259"
FT   ACT_SITE        28
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         28..33
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         59..62
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         59..60
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         88
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         118..120
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         120
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         131..132
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         152
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         156..159
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         165..172
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         183
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         219
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         223
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         275
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   292 AA;  33676 MW;  0660895E1B065E71 CRC64;
     MNFLHQYYQD IIKKKLENLN DKIQCSFEFF PPKNLDTEKK LFSSVVKLSL LKPFLFSVTY
     GANSGERKKT YSIVQRIHKK TGITTAPHLT CVDASLSELK EIAKFYWENG IRSIVALRGD
     VPNKSYQHKI YALDLVVLLK KIADFDISVA AYPEIHPESK NAQSDILNLK KKADAGANRA
     ITQFFFNVES YLRFRDNCIK NNINIEIIPG ILPIYNFEQL KKFSSMTNVS IPKWMFEMFN
     GLDEDLETQK IIGSNIVINI VKTLLYEGVK NFHFYTLNKS DVIYSICHMF GL