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P0AEZ1

- METF_ECOLI

UniProt

P0AEZ1 - METF_ECOLI

Protein

5,10-methylenetetrahydrofolate reductase

Gene

metF

Organism
Escherichia coli (strain K12)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 83 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      Previous versions | rss
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    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

    FAD.6 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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei28 – 281Proton donor/acceptor2 Publications
    Binding sitei88 – 881FAD2 Publications
    Binding sitei120 – 1201Substrate
    Binding sitei152 – 1521FAD2 Publications
    Binding sitei183 – 1831Substrate
    Binding sitei219 – 2191Substrate
    Binding sitei223 – 2231Substrate
    Binding sitei275 – 2751Substrate
    Binding sitei279 – 2791Substrate

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi28 – 336NAD
    Nucleotide bindingi59 – 624FAD2 Publications
    Nucleotide bindingi59 – 602NAD
    Nucleotide bindingi118 – 1203FAD2 Publications
    Nucleotide bindingi131 – 1322FAD2 Publications
    Nucleotide bindingi156 – 1594FAD2 Publications
    Nucleotide bindingi165 – 1728FAD2 Publications

    GO - Molecular functioni

    1. FAD binding Source: EcoCyc
    2. methylenetetrahydrofolate reductase (NAD(P)H) activity Source: EcoCyc

    GO - Biological processi

    1. methionine biosynthetic process Source: UniProtKB-KW
    2. protein homotetramerization Source: EcoCyc
    3. tetrahydrofolate biosynthetic process Source: EcoCyc
    4. tetrahydrofolate interconversion Source: UniProtKB-UniPathway

    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.
    RETL1328306-WGS:GSTH-2918-MONOMER.
    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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

    Organism-specific databases

    EcoGeneiEG10585. metF.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: InterPro

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi28 – 281E → Q: Abolishes enzyme activity. 2 Publications
    Mutagenesisi120 – 1201D → N: Strongly reduces enzyme activity. Strongly reduces affinity for 5-methyltetrahydrofolate. 1 Publication
    Mutagenesisi177 – 1771A → V: Increases the propensity to lose its essential flavin cofactor. 1 Publication
    Mutagenesisi223 – 2231F → A: Strongly decreases substrate and NADH binding. 1 Publication
    Mutagenesisi223 – 2231F → L: Slightly reduced enzyme activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 2962965,10-methylenetetrahydrofolate reductasePRO_0000190261Add
    BLAST

    Proteomic databases

    PaxDbiP0AEZ1.
    PRIDEiP0AEZ1.

    Expressioni

    Inductioni

    Repressed by methionine.1 Publication

    Gene expression databases

    GenevestigatoriP0AEZ1.

    Interactioni

    Subunit structurei

    Homotetramer.3 Publications

    Protein-protein interaction databases

    DIPiDIP-6848N.
    IntActiP0AEZ1. 4 interactions.
    STRINGi511145.b3941.

    Structurei

    Secondary structure

    1
    296
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi4 – 1714
    Turni18 – 214
    Beta strandi24 – 296
    Helixi35 – 4915
    Beta strandi54 – 585
    Helixi67 – 8115
    Beta strandi85 – 917
    Helixi96 – 10813
    Beta strandi113 – 1175
    Beta strandi123 – 1253
    Helixi132 – 14211
    Beta strandi146 – 1516
    Helixi162 – 17514
    Beta strandi179 – 1824
    Helixi188 – 20013
    Beta strandi207 – 2115
    Helixi217 – 22610
    Helixi233 – 2397
    Helixi246 – 26621
    Beta strandi271 – 2755
    Helixi281 – 2899

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 21-295.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0AEZ1.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0685.
    HOGENOMiHOG000246232.
    KOiK00297.
    OMAiFEFFPTK.
    OrthoDBiEOG6D2KVW.
    PhylomeDBiP0AEZ1.

    Family and domain databases

    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

    MSFFHASQRD ALNQSLAEVQ GQINVSFEFF PPRTSEMEQT LWNSIDRLSS    50
    LKPKFVSVTY GANSGERDRT HSIIKGIKDR TGLEAAPHLT CIDATPDELR 100
    TIARDYWNNG IRHIVALRGD LPPGSGKPEM YASDLVTLLK EVADFDISVA 150
    AYPEVHPEAK SAQADLLNLK RKVDAGANRA ITQFFFDVES YLRFRDRCVS 200
    AGIDVEIIPG ILPVSNFKQA KKFADMTNVR IPAWMAQMFD GLDDDAETRK 250
    LVGANIAMDM VKILSREGVK DFHFYTLNRA EMSYAICHTL GVRPGL 296
    Length:296
    Mass (Da):33,103
    Last modified:July 21, 1986 - v1
    Checksum:iB702702D2BE9521E
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    YP_491510.1. NC_007779.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76923; AAC76923; b3941.
    BAE77369; BAE77369; BAE77369.
    GeneIDi12934069.
    948432.
    KEGGiecj:Y75_p3246.
    eco:b3941.
    PATRICi32123403. VBIEscCol129921_4062.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    PIRi A00462. RDECMH.
    RefSeqi NP_418376.1. NC_000913.3.
    YP_491510.1. NC_007779.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1B5T X-ray 2.50 A/B/C 21-294 [» ]
    1ZP3 X-ray 1.85 A/B/C 1-296 [» ]
    1ZP4 X-ray 1.85 A/B/C 1-296 [» ]
    1ZPT X-ray 1.95 A/B/C 1-296 [» ]
    1ZRQ X-ray 2.20 A/B/C 1-296 [» ]
    2FMN X-ray 2.05 A/B/C 1-296 [» ]
    2FMO X-ray 2.25 A/B/C 1-296 [» ]
    3FST X-ray 1.65 A/C/E 1-296 [» ]
    3FSU X-ray 1.70 A/C/E 1-296 [» ]
    ProteinModelPortali P0AEZ1.
    SMRi P0AEZ1. Positions 21-295.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-6848N.
    IntActi P0AEZ1. 4 interactions.
    STRINGi 511145.b3941.

    Proteomic databases

    PaxDbi P0AEZ1.
    PRIDEi P0AEZ1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblBacteriai AAC76923 ; AAC76923 ; b3941 .
    BAE77369 ; BAE77369 ; BAE77369 .
    GeneIDi 12934069.
    948432.
    KEGGi ecj:Y75_p3246.
    eco:b3941.
    PATRICi 32123403. VBIEscCol129921_4062.

    Organism-specific databases

    EchoBASEi EB0580.
    EcoGenei EG10585. metF.

    Phylogenomic databases

    eggNOGi COG0685.
    HOGENOMi HOG000246232.
    KOi K00297.
    OMAi FEFFPTK.
    OrthoDBi EOG6D2KVW.
    PhylomeDBi P0AEZ1.

    Enzyme and pathway databases

    UniPathwayi UPA00193 .
    BioCyci EcoCyc:METHYLENETHFREDUCT-MONOMER.
    ECOL316407:JW3913-MONOMER.
    MetaCyc:METHYLENETHFREDUCT-MONOMER.
    RETL1328306-WGS:GSTH-2918-MONOMER.

    Miscellaneous databases

    EvolutionaryTracei P0AEZ1.
    PROi P0AEZ1.

    Gene expression databases

    Genevestigatori P0AEZ1.

    Family and domain databases

    Gene3Di 3.20.20.220. 1 hit.
    InterProi IPR029041. FAD-linked_oxidoreductase-like.
    IPR003171. Mehydrof_redctse.
    IPR004620. MTHF_reductase_bac.
    [Graphical view ]
    Pfami PF02219. MTHFR. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51730. SSF51730. 1 hit.
    TIGRFAMsi TIGR00676. fadh2. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Nucleotide sequence of metF, the E. coli structural gene for 5-10 methylene tetrahydrofolate reductase and of its control region."
      Saint-Girons I., Duchange N., Zakin M.M., Park I., Margarita D., Ferrara P., Cohen G.N.
      Nucleic Acids Res. 11:6723-6732(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    2. "Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes."
      Plunkett G. III, Burland V., Daniels D.L., Blattner F.R.
      Nucleic Acids Res. 21:3391-3398(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    5. "Enzymatic synthesis of the methyl group of methionine. 8. Repression-derepression, purification, and properties of 5,10-methylenetetrahydrofolate reductase from Escherichia coli."
      Katzen H.M., Buchanan J.M.
      J. Biol. Chem. 240:825-835(1965) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR.
    6. "Construction and physical mapping of plasmids containing the metJBLF gene cluster of E. coli K12."
      Zakin M.M., Greene R.C., Dautry-Varsat A., Duchange N., Ferrara P., Py M.C., Margarita D., Cohen G.N.
      Mol. Gen. Genet. 187:101-106(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION.
    7. "Folate activation and catalysis in methylenetetrahydrofolate reductase from Escherichia coli: roles for aspartate 120 and glutamate 28."
      Trimmer E.E., Ballou D.P., Ludwig M.L., Matthews R.G.
      Biochemistry 40:6216-6226(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, COFACTOR, ACTIVE SITE, MUTAGENESIS OF GLU-28 AND ASP-120.
    8. "The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia."
      Guenther B.D., Sheppard C.A., Tran P., Rozen R., Matthews R.G., Ludwig M.L.
      Nat. Struct. Biol. 6:359-365(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 21-294 IN COMPLEX WITH FAD, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, MUTAGENESIS OF ALA-177.
    9. "Structures of NADH and CH3-H4folate complexes of Escherichia coli methylenetetrahydrofolate reductase reveal a spartan strategy for a ping-pong reaction."
      Pejchal R., Sargeant R., Ludwig M.L.
      Biochemistry 44:11447-11457(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF WILD TYPE AND MUTANT GLN-28 IN COMPLEXES WITH 5-METHYL-5,6,7,8-TETRAHYDROFOLATE; FAD AND NAD, COFACTOR, SUBUNIT, MUTAGENESIS OF GLU-28, ACTIVE SITE.
    10. "Structural perturbations in the Ala --> Val polymorphism of methylenetetrahydrofolate reductase: how binding of folates may protect against inactivation."
      Pejchal R., Campbell E., Guenther B.D., Lennon B.W., Matthews R.G., Ludwig M.L.
      Biochemistry 45:4808-4818(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF MUTANT VAL-177 IN COMPLEX WITH SUBSTRATE ANALOG LY309887 AND FAD, COFACTOR, SUBUNIT.
    11. "Functional role for the conformationally mobile phenylalanine 223 in the reaction of methylenetetrahydrofolate reductase from Escherichia coli."
      Lee M.N., Takawira D., Nikolova A.P., Ballou D.P., Furtado V.C., Phung N.L., Still B.R., Thorstad M.K., Tanner J.J., Trimmer E.E.
      Biochemistry 48:7673-7685(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) ON MUTANTS GLN-28 AND LEU-223 IN COMPLEXES WITH 5-METHYL-5,6,7,8-TETRAHYDROFOLATE AND FAD, CATALYTIC ACTIVITY, MUTAGENESIS OF PHE-223, COFACTOR.

    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: October 1, 2014
    This is version 83 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

    External Data

    Dasty 3