Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine hydroxymethyltransferase

Gene

glyA

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

Functioni

Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier. This reaction serves as the major source of one-carbon groups required for the biosynthesis of purines, thymidylate, methionine, and other important biomolecules. Also exhibits THF-independent aldolase activity toward beta-hydroxyamino acids, producing glycine and aldehydes, via a retro-aldol mechanism. Thus, is able to catalyze the cleavage of allothreonine and 3-phenylserine. Also catalyzes the irreversible conversion of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate.1 Publication

Catalytic activityi

5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine.

Cofactori

Kineticsi

  1. KM=7 µM for tetrahydrofolate2 Publications
  2. KM=140 µM for serine2 Publications
  3. KM=300 µM for serine2 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.

    Pathwayi: glycine biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes glycine from L-serine.
    Proteins known to be involved in this subpathway in this organism are:
    1. Serine hydroxymethyltransferase (glyA)
    This subpathway is part of the pathway glycine biosynthesis, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes glycine from L-serine, the pathway glycine biosynthesis and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei35Pyridoxal phosphate2 Publications1
    Binding sitei55Pyridoxal phosphate2 Publications1
    Sitei55Transaldimination and stability1
    Binding sitei57Substrate1
    Binding sitei64Substrate1
    Binding sitei65Pyridoxal phosphate2 Publications1
    Binding sitei99Pyridoxal phosphate2 Publications1
    Binding sitei121Substrate; via carbonyl oxygen1
    Binding sitei175Pyridoxal phosphate2 Publications1
    Binding sitei203Pyridoxal phosphate2 Publications1
    Binding sitei228Pyridoxal phosphate2 Publications1
    Binding sitei235Pyridoxal phosphate2 Publications1
    Sitei235Transaldimination and stability1
    Binding sitei246Substrate1
    Binding sitei263Pyridoxal phosphate; via amide nitrogen and carbonyl oxygen2 Publications1
    Binding sitei363Pyridoxal phosphate2 Publications1

    GO - Molecular functioni

    • glycine hydroxymethyltransferase activity Source: EcoCyc
    • identical protein binding Source: IntAct
    • pyridoxal phosphate binding Source: EcoCyc
    • zinc ion binding Source: EcoliWiki

    GO - Biological processi

    • glycine biosynthetic process from serine Source: EcoCyc
    • glycine catabolic process Source: EcoCyc
    • L-serine catabolic process Source: EcoCyc
    • tetrahydrofolate interconversion Source: UniProtKB-UniPathway
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Amino-acid biosynthesis, One-carbon metabolism

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciEcoCyc:GLYOHMETRANS-MONOMER.
    ECOL316407:JW2535-MONOMER.
    MetaCyc:GLYOHMETRANS-MONOMER.
    BRENDAi2.1.2.1. 2026.
    4.1.2.48. 2026.
    UniPathwayiUPA00193.
    UPA00288; UER01023.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine hydroxymethyltransferase (EC:2.1.2.1)
    Short name:
    SHMT
    Short name:
    Serine methylase
    Gene namesi
    Name:glyA
    Ordered Locus Names:b2551, JW2535
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10408. glyA.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi55Y → F: 50 and 15-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 4-fold decrease in the catalytic efficiency. 1 Publication1
    Mutagenesisi65Y → F: Decrease in catalytic activity. 1 Publication1
    Mutagenesisi85L → A: Alteration of the dimer-monomer equilibrium accompanied by minor changes in the catalytic properties and whitout any significant change of tertiary structure. In the monomeric state; when associated with A-276. 1 Publication1
    Mutagenesisi214P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. 1 Publication1
    Mutagenesisi214P → G: No significant difference in catalytic efficiency and affinity compared to the wild-type. 1 Publication1
    Mutagenesisi216P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. Alteration in the folding rate. 1 Publication1
    Mutagenesisi216P → G: Important decrease in affinity and catalytic efficiency. Severely compromised in folding into a catalytically competent enzyme. 1 Publication1
    Mutagenesisi218P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. 1 Publication1
    Mutagenesisi218P → G: No significant difference in catalytic efficiency and affinity compared to the wild-type. 1 Publication1
    Mutagenesisi235R → K: 1500- and 20-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 15-fold decrease in the catalytic efficiency. 1 Publication1
    Mutagenesisi235R → L: 450- and 11-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 60-fold decrease in the catalytic efficiency. 1 Publication1
    Mutagenesisi235R → Q: 900- and 17-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 30-fold decrease in the catalytic efficiency. 1 Publication1
    Mutagenesisi258P → A: Important decrease in affinity and catalytic efficiency. Reduced thermal stability. 1 Publication1
    Mutagenesisi258P → G: Important decrease in affinity and catalytic efficiency. 1 Publication1
    Mutagenesisi264P → A: Important decrease in affinity and catalytic efficiency. 1 Publication1
    Mutagenesisi264P → G: Important decrease in affinity and catalytic efficiency. 1 Publication1
    Mutagenesisi276L → A: Alteration of the dimer-monomer equilibrium accompanied by minor changes in the catalytic properties and whitout any significant change of tertiary structure. In the monomeric state; when associated with A-85. 1 Publication1
    Mutagenesisi363R → A: It does not bind serine and glycine and shows no activity with serine as the substrate. 1 Publication1
    Mutagenesisi363R → K: Exhibits only 0.03% of the catalytic activity of the wild-type and a 15-fold reduction in affinity for glycine and serine. 1 Publication1
    Mutagenesisi372R → A: No significant difference compared to the wild-type. 1 Publication1
    Mutagenesisi372R → K: No significant difference compared to the wild-type. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001135731 – 417Serine hydroxymethyltransferaseAdd BLAST417

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei54N6-acetyllysine1 Publication1
    Modified residuei62N6-succinyllysine1 Publication1
    Modified residuei229N6-(pyridoxal phosphate)lysine1
    Modified residuei242N6-succinyllysine1 Publication1
    Modified residuei250N6-acetyllysine; alternate1 Publication1
    Modified residuei250N6-succinyllysine; alternate1 Publication1
    Modified residuei277N6-succinyllysine1 Publication1
    Modified residuei285N6-acetyllysine1 Publication1
    Modified residuei293N6-succinyllysine1 Publication1
    Modified residuei331N6-succinyllysine1 Publication1
    Modified residuei346N6-succinyllysine1 Publication1
    Modified residuei354N6-acetyllysine; alternate1 Publication1
    Modified residuei354N6-succinyllysine; alternate1 Publication1
    Modified residuei375N6-acetyllysine1 Publication1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    EPDiP0A825.
    PaxDbiP0A825.
    PRIDEiP0A825.

    2D gel databases

    SWISS-2DPAGEP0A825.

    Expressioni

    Inductioni

    By CsgD.1 Publication

    Interactioni

    Subunit structurei

    Homodimer.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself5EBI-909080,EBI-909080

    GO - Molecular functioni

    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi4261314. 203 interactors.
    DIPiDIP-36205N.
    IntActiP0A825. 7 interactors.
    MINTiMINT-7293373.
    STRINGi511145.b2551.

    Structurei

    Secondary structure

    1417
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi8 – 11Combined sources4
    Helixi13 – 28Combined sources16
    Beta strandi29 – 31Combined sources3
    Helixi41 – 47Combined sources7
    Helixi50 – 53Combined sources4
    Beta strandi62 – 66Combined sources5
    Helixi69 – 86Combined sources18
    Beta strandi89 – 92Combined sources4
    Helixi98 – 109Combined sources12
    Beta strandi115 – 119Combined sources5
    Turni121 – 124Combined sources4
    Helixi127 – 129Combined sources3
    Helixi135 – 139Combined sources5
    Beta strandi140 – 145Combined sources6
    Beta strandi149 – 152Combined sources4
    Helixi155 – 165Combined sources11
    Beta strandi168 – 173Combined sources6
    Helixi183 – 192Combined sources10
    Beta strandi196 – 200Combined sources5
    Turni202 – 204Combined sources3
    Helixi205 – 209Combined sources5
    Turni217 – 219Combined sources3
    Beta strandi220 – 229Combined sources10
    Beta strandi237 – 243Combined sources7
    Helixi246 – 256Combined sources11
    Turni257 – 260Combined sources4
    Helixi266 – 278Combined sources13
    Helixi282 – 304Combined sources23
    Helixi310 – 312Combined sources3
    Beta strandi315 – 322Combined sources8
    Helixi324 – 326Combined sources3
    Helixi330 – 339Combined sources10
    Turni356 – 358Combined sources3
    Beta strandi360 – 365Combined sources6
    Helixi367 – 371Combined sources5
    Helixi376 – 391Combined sources16
    Turni392 – 394Combined sources3
    Helixi396 – 412Combined sources17
    Beta strandi415 – 417Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1DFOX-ray2.40A/B/C/D1-417[»]
    1EQBX-ray2.70A/B/C/D1-417[»]
    3G8MX-ray3.30A1-417[»]
    ProteinModelPortaliP0A825.
    SMRiP0A825.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0A825.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni125 – 127Substrate binding3
    Regioni355 – 357Substrate binding3

    Sequence similaritiesi

    Belongs to the SHMT family.Curated

    Phylogenomic databases

    eggNOGiENOG4105C65. Bacteria.
    COG0112. LUCA.
    HOGENOMiHOG000239404.
    InParanoidiP0A825.
    KOiK00600.
    OMAiDANNPAV.
    PhylomeDBiP0A825.

    Family and domain databases

    CDDicd00378. SHMT. 1 hit.
    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    HAMAPiMF_00051. SHMT. 1 hit.
    InterProiIPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    IPR001085. Ser_HO-MeTrfase.
    IPR019798. Ser_HO-MeTrfase_PLP_BS.
    [Graphical view]
    PANTHERiPTHR11680. PTHR11680. 1 hit.
    PfamiPF00464. SHMT. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000412. SHMT. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00096. SHMT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P0A825-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLKREMNIAD YDAELWQAME QEKVRQEEHI ELIASENYTS PRVMQAQGSQ
    60 70 80 90 100
    LTNKYAEGYP GKRYYGGCEY VDIVEQLAID RAKELFGADY ANVQPHSGSQ
    110 120 130 140 150
    ANFAVYTALL EPGDTVLGMN LAHGGHLTHG SPVNFSGKLY NIVPYGIDAT
    160 170 180 190 200
    GHIDYADLEK QAKEHKPKMI IGGFSAYSGV VDWAKMREIA DSIGAYLFVD
    210 220 230 240 250
    MAHVAGLVAA GVYPNPVPHA HVVTTTTHKT LAGPRGGLIL AKGGSEELYK
    260 270 280 290 300
    KLNSAVFPGG QGGPLMHVIA GKAVALKEAM EPEFKTYQQQ VAKNAKAMVE
    310 320 330 340 350
    VFLERGYKVV SGGTDNHLFL VDLVDKNLTG KEADAALGRA NITVNKNSVP
    360 370 380 390 400
    NDPKSPFVTS GIRVGTPAIT RRGFKEAEAK ELAGWMCDVL DSINDEAVIE
    410
    RIKGKVLDIC ARYPVYA
    Length:417
    Mass (Da):45,317
    Last modified:July 21, 1986 - v1
    Checksum:i13E5558E99938539
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    V00283 Genomic DNA. Translation: CAA23547.1.
    U00096 Genomic DNA. Translation: AAC75604.1.
    AP009048 Genomic DNA. Translation: BAA16459.1.
    J01620 Genomic DNA. Translation: AAA23912.1.
    PIRiA00559. XYECS.
    RefSeqiNP_417046.1. NC_000913.3.
    WP_000919159.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75604; AAC75604; b2551.
    BAA16459; BAA16459; BAA16459.
    GeneIDi947022.
    KEGGiecj:JW2535.
    eco:b2551.
    PATRICi32120501. VBIEscCol129921_2653.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    V00283 Genomic DNA. Translation: CAA23547.1.
    U00096 Genomic DNA. Translation: AAC75604.1.
    AP009048 Genomic DNA. Translation: BAA16459.1.
    J01620 Genomic DNA. Translation: AAA23912.1.
    PIRiA00559. XYECS.
    RefSeqiNP_417046.1. NC_000913.3.
    WP_000919159.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1DFOX-ray2.40A/B/C/D1-417[»]
    1EQBX-ray2.70A/B/C/D1-417[»]
    3G8MX-ray3.30A1-417[»]
    ProteinModelPortaliP0A825.
    SMRiP0A825.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4261314. 203 interactors.
    DIPiDIP-36205N.
    IntActiP0A825. 7 interactors.
    MINTiMINT-7293373.
    STRINGi511145.b2551.

    2D gel databases

    SWISS-2DPAGEP0A825.

    Proteomic databases

    EPDiP0A825.
    PaxDbiP0A825.
    PRIDEiP0A825.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC75604; AAC75604; b2551.
    BAA16459; BAA16459; BAA16459.
    GeneIDi947022.
    KEGGiecj:JW2535.
    eco:b2551.
    PATRICi32120501. VBIEscCol129921_2653.

    Organism-specific databases

    EchoBASEiEB0403.
    EcoGeneiEG10408. glyA.

    Phylogenomic databases

    eggNOGiENOG4105C65. Bacteria.
    COG0112. LUCA.
    HOGENOMiHOG000239404.
    InParanoidiP0A825.
    KOiK00600.
    OMAiDANNPAV.
    PhylomeDBiP0A825.

    Enzyme and pathway databases

    UniPathwayiUPA00193.
    UPA00288; UER01023.
    BioCyciEcoCyc:GLYOHMETRANS-MONOMER.
    ECOL316407:JW2535-MONOMER.
    MetaCyc:GLYOHMETRANS-MONOMER.
    BRENDAi2.1.2.1. 2026.
    4.1.2.48. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP0A825.
    PROiP0A825.

    Family and domain databases

    CDDicd00378. SHMT. 1 hit.
    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    HAMAPiMF_00051. SHMT. 1 hit.
    InterProiIPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    IPR001085. Ser_HO-MeTrfase.
    IPR019798. Ser_HO-MeTrfase_PLP_BS.
    [Graphical view]
    PANTHERiPTHR11680. PTHR11680. 1 hit.
    PfamiPF00464. SHMT. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000412. SHMT. 1 hit.
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00096. SHMT. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiGLYA_ECOLI
    AccessioniPrimary (citable) accession number: P0A825
    Secondary accession number(s): P00477
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: November 2, 2016
    This is version 104 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, Direct protein sequencing, 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.