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Protein

5,10-methylenetetrahydrofolate reductase

Gene

metF

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Methylenetetrahydrofolate reductase required to generate the methyl groups necessary for methionine synthetase to convert homocysteine to methionine.1 Publication

Catalytic activityi

5-methyltetrahydrofolate + NAD(P)+ = 5,10-methylenetetrahydrofolate + NAD(P)H.3 Publications

Cofactori

FAD6 Publications

Kineticsi

  1. KM=17 µM for NADPH2 Publications
  2. KM=3.9 µM for 5,10-methylenetetrahydrofolate2 Publications

    pH dependencei

    Optimum pH is 6.3-6.4.2 Publications

    Pathwayi: tetrahydrofolate interconversion

    This protein is involved in the pathway tetrahydrofolate interconversion, which is part of One-carbon metabolism.
    View all proteins of this organism that are known to be involved in the pathway tetrahydrofolate interconversion and in One-carbon metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei28Proton donor/acceptor2 Publications1
    Binding sitei88FAD2 Publications1
    Binding sitei120Substrate1
    Binding sitei152FAD2 Publications1
    Binding sitei183Substrate1
    Binding sitei219Substrate1
    Binding sitei223Substrate1
    Binding sitei275Substrate1
    Binding sitei279Substrate1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi28 – 33NAD6
    Nucleotide bindingi59 – 62FAD2 Publications4
    Nucleotide bindingi59 – 60NAD2
    Nucleotide bindingi118 – 120FAD2 Publications3
    Nucleotide bindingi131 – 132FAD2 Publications2
    Nucleotide bindingi156 – 159FAD2 Publications4
    Nucleotide bindingi165 – 172FAD2 Publications8

    GO - Molecular functioni

    • FAD binding Source: EcoCyc
    • methylenetetrahydrofolate reductase (NAD(P)H) activity Source: EcoCyc

    GO - Biological processi

    • methionine biosynthetic process Source: UniProtKB-KW
    • one-carbon metabolic process Source: GO_Central
    • protein homotetramerization Source: EcoCyc
    • tetrahydrofolate biosynthetic process Source: EcoCyc
    • tetrahydrofolate interconversion Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Methionine biosynthesis

    Keywords - Ligandi

    FAD, Flavoprotein, NAD, NADP

    Enzyme and pathway databases

    BioCyciEcoCyc:METHYLENETHFREDUCT-MONOMER.
    ECOL316407:JW3913-MONOMER.
    MetaCyc:METHYLENETHFREDUCT-MONOMER.
    BRENDAi1.5.1.20. 2026.
    UniPathwayiUPA00193.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    5,10-methylenetetrahydrofolate reductase (EC:1.5.1.20)
    Gene namesi
    Name:metF
    Ordered Locus Names:b3941, JW3913
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10585. metF.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi28E → Q: Abolishes enzyme activity. 2 Publications1
    Mutagenesisi120D → N: Strongly reduces enzyme activity. Strongly reduces affinity for 5-methyltetrahydrofolate. 1 Publication1
    Mutagenesisi177A → V: Increases the propensity to lose its essential flavin cofactor. 1 Publication1
    Mutagenesisi223F → A: Strongly decreases substrate and NADH binding. 1 Publication1
    Mutagenesisi223F → L: Slightly reduced enzyme activity. 1 Publication1

    Chemistry databases

    DrugBankiDB03147. Flavin adenine dinucleotide.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001902611 – 2965,10-methylenetetrahydrofolate reductaseAdd BLAST296

    Proteomic databases

    EPDiP0AEZ1.
    PaxDbiP0AEZ1.
    PRIDEiP0AEZ1.

    Expressioni

    Inductioni

    Repressed by methionine.1 Publication

    Interactioni

    Subunit structurei

    Homotetramer.3 Publications

    Protein-protein interaction databases

    BioGridi4263063. 13 interactors.
    DIPiDIP-6848N.
    IntActiP0AEZ1. 4 interactors.
    STRINGi511145.b3941.

    Structurei

    Secondary structure

    1296
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi4 – 17Combined sources14
    Turni18 – 21Combined sources4
    Beta strandi24 – 29Combined sources6
    Helixi35 – 49Combined sources15
    Beta strandi54 – 58Combined sources5
    Helixi67 – 81Combined sources15
    Beta strandi85 – 91Combined sources7
    Helixi96 – 108Combined sources13
    Beta strandi113 – 117Combined sources5
    Beta strandi123 – 125Combined sources3
    Helixi132 – 142Combined sources11
    Beta strandi146 – 151Combined sources6
    Helixi162 – 175Combined sources14
    Beta strandi179 – 182Combined sources4
    Helixi188 – 200Combined sources13
    Beta strandi207 – 211Combined sources5
    Helixi217 – 226Combined sources10
    Helixi233 – 239Combined sources7
    Helixi246 – 266Combined sources21
    Beta strandi271 – 275Combined sources5
    Helixi281 – 289Combined sources9

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1B5TX-ray2.50A/B/C21-294[»]
    1ZP3X-ray1.85A/B/C1-296[»]
    1ZP4X-ray1.85A/B/C1-296[»]
    1ZPTX-ray1.95A/B/C1-296[»]
    1ZRQX-ray2.20A/B/C1-296[»]
    2FMNX-ray2.05A/B/C1-296[»]
    2FMOX-ray2.25A/B/C1-296[»]
    3FSTX-ray1.65A/C/E1-296[»]
    3FSUX-ray1.70A/C/E1-296[»]
    ProteinModelPortaliP0AEZ1.
    SMRiP0AEZ1.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0AEZ1.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4105SYT. Bacteria.
    COG0685. LUCA.
    HOGENOMiHOG000246232.
    InParanoidiP0AEZ1.
    KOiK00297.
    OMAiEMHPQAR.
    PhylomeDBiP0AEZ1.

    Family and domain databases

    CDDicd00537. MTHFR. 1 hit.
    Gene3Di3.20.20.220. 1 hit.
    InterProiIPR029041. FAD-linked_oxidoreductase-like.
    IPR003171. Mehydrof_redctse.
    IPR004620. MTHF_reductase_bac.
    [Graphical view]
    PfamiPF02219. MTHFR. 1 hit.
    [Graphical view]
    SUPFAMiSSF51730. SSF51730. 1 hit.
    TIGRFAMsiTIGR00676. fadh2. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P0AEZ1-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSFFHASQRD ALNQSLAEVQ GQINVSFEFF PPRTSEMEQT LWNSIDRLSS
    60 70 80 90 100
    LKPKFVSVTY GANSGERDRT HSIIKGIKDR TGLEAAPHLT CIDATPDELR
    110 120 130 140 150
    TIARDYWNNG IRHIVALRGD LPPGSGKPEM YASDLVTLLK EVADFDISVA
    160 170 180 190 200
    AYPEVHPEAK SAQADLLNLK RKVDAGANRA ITQFFFDVES YLRFRDRCVS
    210 220 230 240 250
    AGIDVEIIPG ILPVSNFKQA KKFADMTNVR IPAWMAQMFD GLDDDAETRK
    260 270 280 290
    LVGANIAMDM VKILSREGVK DFHFYTLNRA EMSYAICHTL GVRPGL
    Length:296
    Mass (Da):33,103
    Last modified:July 21, 1986 - v1
    Checksum:iB702702D2BE9521E
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    V01502 Genomic DNA. Translation: CAA24747.1.
    L19201 Genomic DNA. Translation: AAB03073.1.
    U00096 Genomic DNA. Translation: AAC76923.1.
    AP009048 Genomic DNA. Translation: BAE77369.1.
    PIRiA00462. RDECMH.
    RefSeqiNP_418376.1. NC_000913.3.
    WP_000007523.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76923; AAC76923; b3941.
    BAE77369; BAE77369; BAE77369.
    GeneIDi948432.
    KEGGiecj:JW3913.
    eco:b3941.
    PATRICi32123403. VBIEscCol129921_4062.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    V01502 Genomic DNA. Translation: CAA24747.1.
    L19201 Genomic DNA. Translation: AAB03073.1.
    U00096 Genomic DNA. Translation: AAC76923.1.
    AP009048 Genomic DNA. Translation: BAE77369.1.
    PIRiA00462. RDECMH.
    RefSeqiNP_418376.1. NC_000913.3.
    WP_000007523.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1B5TX-ray2.50A/B/C21-294[»]
    1ZP3X-ray1.85A/B/C1-296[»]
    1ZP4X-ray1.85A/B/C1-296[»]
    1ZPTX-ray1.95A/B/C1-296[»]
    1ZRQX-ray2.20A/B/C1-296[»]
    2FMNX-ray2.05A/B/C1-296[»]
    2FMOX-ray2.25A/B/C1-296[»]
    3FSTX-ray1.65A/C/E1-296[»]
    3FSUX-ray1.70A/C/E1-296[»]
    ProteinModelPortaliP0AEZ1.
    SMRiP0AEZ1.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4263063. 13 interactors.
    DIPiDIP-6848N.
    IntActiP0AEZ1. 4 interactors.
    STRINGi511145.b3941.

    Chemistry databases

    DrugBankiDB03147. Flavin adenine dinucleotide.

    Proteomic databases

    EPDiP0AEZ1.
    PaxDbiP0AEZ1.
    PRIDEiP0AEZ1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC76923; AAC76923; b3941.
    BAE77369; BAE77369; BAE77369.
    GeneIDi948432.
    KEGGiecj:JW3913.
    eco:b3941.
    PATRICi32123403. VBIEscCol129921_4062.

    Organism-specific databases

    EchoBASEiEB0580.
    EcoGeneiEG10585. metF.

    Phylogenomic databases

    eggNOGiENOG4105SYT. Bacteria.
    COG0685. LUCA.
    HOGENOMiHOG000246232.
    InParanoidiP0AEZ1.
    KOiK00297.
    OMAiEMHPQAR.
    PhylomeDBiP0AEZ1.

    Enzyme and pathway databases

    UniPathwayiUPA00193.
    BioCyciEcoCyc:METHYLENETHFREDUCT-MONOMER.
    ECOL316407:JW3913-MONOMER.
    MetaCyc:METHYLENETHFREDUCT-MONOMER.
    BRENDAi1.5.1.20. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP0AEZ1.
    PROiP0AEZ1.

    Family and domain databases

    CDDicd00537. MTHFR. 1 hit.
    Gene3Di3.20.20.220. 1 hit.
    InterProiIPR029041. FAD-linked_oxidoreductase-like.
    IPR003171. Mehydrof_redctse.
    IPR004620. MTHF_reductase_bac.
    [Graphical view]
    PfamiPF02219. MTHFR. 1 hit.
    [Graphical view]
    SUPFAMiSSF51730. SSF51730. 1 hit.
    TIGRFAMsiTIGR00676. fadh2. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMETF_ECOLI
    AccessioniPrimary (citable) accession number: P0AEZ1
    Secondary accession number(s): P00394, Q2M8N7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: November 2, 2016
    This is version 100 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.