ID   MTHR1_MAIZE             Reviewed;         593 AA.
AC   Q9SE94;
DT   22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Methylenetetrahydrofolate reductase 1;
DE            EC=1.5.1.20;
DE   AltName: Full=ZmMTHFR1;
OS   Zea mays (Maize).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; Liliopsida; Poales; Poaceae; PACMAD clade;
OC   Panicoideae; Andropogonodae; Andropogoneae; Tripsacinae; Zea.
OX   NCBI_TaxID=4577;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND ACTIVITY REGULATION.
RX   PubMed=10593891; DOI=10.1074/jbc.274.51.36089;
RA   Roje S., Wang H., McNeil S.D., Raymond R.K., Appling D.R., Shachar-Hill Y.,
RA   Bohnert H.J., Hanson A.D.;
RT   "Isolation, characterization, and functional expression of cDNAs encoding
RT   NADH-dependent methylenetetrahydrofolate reductase from higher plants.";
RL   J. Biol. Chem. 274:36089-36096(1999).
CC   -!- FUNCTION: The probable reversibility of the MTHFR reaction in plants
CC       suggests that they can metabolize the methyl group of 5,10-
CC       methylenetetrahydrofolate to serine, sugars and starch.
CC       {ECO:0000269|PubMed:10593891}.
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   -!- ACTIVITY REGULATION: Plant MTHFRs strongly prefer NADH over NADPH. Not
CC       inhibited by methionine or S-adenosylmethionine.
CC       {ECO:0000269|PubMed:10593891}.
CC   -!- PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the methylenetetrahydrofolate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; AF174486; AAD51733.1; -; mRNA.
DR   RefSeq; NP_001104947.1; NM_001111477.2.
DR   AlphaFoldDB; Q9SE94; -.
DR   SMR; Q9SE94; -.
DR   STRING; 4577.GRMZM2G347056_P01; -.
DR   PaxDb; Q9SE94; -.
DR   PRIDE; Q9SE94; -.
DR   ProMEX; Q9SE94; -.
DR   EnsemblPlants; Zm00001eb062180_T001; Zm00001eb062180_P001; Zm00001eb062180.
DR   EnsemblPlants; Zm00001eb062180_T002; Zm00001eb062180_P002; Zm00001eb062180.
DR   EnsemblPlants; Zm00001eb062180_T003; Zm00001eb062180_P003; Zm00001eb062180.
DR   GeneID; 541794; -.
DR   Gramene; Zm00001eb062180_T001; Zm00001eb062180_P001; Zm00001eb062180.
DR   Gramene; Zm00001eb062180_T002; Zm00001eb062180_P002; Zm00001eb062180.
DR   Gramene; Zm00001eb062180_T003; Zm00001eb062180_P003; Zm00001eb062180.
DR   KEGG; zma:541794; -.
DR   MaizeGDB; 146840; -.
DR   eggNOG; KOG0564; Eukaryota.
DR   HOGENOM; CLU_025841_2_2_1; -.
DR   OMA; IGWDEFP; -.
DR   OrthoDB; 338303at2759; -.
DR   BRENDA; 1.5.1.20; 6752.
DR   BRENDA; 1.5.1.54; 6752.
DR   UniPathway; UPA00193; -.
DR   Proteomes; UP000007305; Chromosome 1.
DR   ExpressionAtlas; Q9SE94; baseline and differential.
DR   Genevisible; Q9SE94; ZM.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
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:0106313; F:methylenetetrahydrofolate reductase NADPH 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   InterPro; IPR029041; FAD-linked_oxidoreductase-like.
DR   InterPro; IPR004621; Fadh2_euk.
DR   InterPro; IPR003171; Mehydrof_redctse-like.
DR   Pfam; PF02219; MTHFR; 1.
DR   SUPFAM; SSF51730; SSF51730; 1.
DR   TIGRFAMs; TIGR00677; fadh2_euk; 1.
PE   2: Evidence at transcript level;
KW   FAD; Flavoprotein; NAD; Oxidoreductase; Reference proteome.
FT   CHAIN           1..593
FT                   /note="Methylenetetrahydrofolate reductase 1"
FT                   /id="PRO_0000190251"
FT   ACT_SITE        21
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         21..26
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         52..53
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         52..53
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         81
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         111..113
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         113
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         153
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         157..160
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         175
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         182
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         193
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         285
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   593 AA;  66429 MW;  4568996775B638B4 CRC64;
     MKVIEKILEA AGDGRTAFSF EYFPPKTEEG VENLFERMDR MVAHGPSFCD ITWGAGGSTA
     DLTLEIANRM QNMVCVETMM HLTCTNMPVE KIDHALETIK SNGIQNVLAL RGDPPHGQDK
     FVQVEGGFAC ALDLVQHIRA KYGDYFGITV AGYPEAHPDA IQGEGGATLE AYSNDLAYLK
     RKVDAGADLI VTQLFYDTDI FLKFVNDCRQ IGITCPIVPG IMPINNYKGF LRMTGFCKTK
     IPSEITAALD PIKDNEEAVR QYGIHLGTEM CKKILATGIK TLHLYTLNMD KSAIGILMNL
     GLIEESKVSR PLPWRPATNV FRVKEDVRPI FWANRPKSYL KRTLGWDQYP HGRWGDSRNP
     SYGALTDHQF TRPRGRGKKL QEEWAVPLKS VEDISERFTN FCQGKLTSSP WSELDGLQPE
     TKIIDDQLVN INQKGFLTIN SQPAVNGEKS DSPTVGWGGP GGYVYQKAYL EFFCAKEKLD
     QLIEKIKAFP SLTYIAVNKD GETFSNISPN AVNAVTWGVF PGKEIIQPTV VDHASFMVWK
     DEAFEIWTRG WGCMFPEGDS SRELLEKVQK TYYLVSLVDN DYVQGDLFAA FKI