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P0A825 (GLYA_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine hydroxymethyltransferase

Short name=SHMT
Short name=Serine methylase
EC=2.1.2.1
Gene names
Name:glyA
Ordered Locus Names:b2551, JW2535
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length417 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Catalytic activity

5,10-methylenetetrahydrofolate + glycine + H2O = tetrahydrofolate + L-serine. HAMAP-Rule MF_00051

Cofactor

Pyridoxal phosphate.

Pathway

One-carbon metabolism; tetrahydrofolate interconversion. HAMAP-Rule MF_00051

Amino-acid biosynthesis; glycine biosynthesis; glycine from L-serine: step 1/1. HAMAP-Rule MF_00051

Subunit structure

Homodimer. Ref.15 Ref.18

Subcellular location

Cytoplasm HAMAP-Rule MF_00051.

Induction

By CsgD. Ref.12

Sequence similarities

Belongs to the SHMT family.

Biophysicochemical properties

Kinetic parameters:

KM=7 µM for tetrahydrofolate (Ref.19) Ref.11 Ref.19

KM=140 µM for serine (Ref.19)

KM=300 µM for serine (Ref.11)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself5EBI-909080,EBI-909080

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 417417Serine hydroxymethyltransferase HAMAP-Rule MF_00051
PRO_0000113573

Regions

Region125 – 1273Substrate binding HAMAP-Rule MF_00051
Region355 – 3573Substrate binding HAMAP-Rule MF_00051

Sites

Binding site351Pyridoxal phosphate
Binding site551Pyridoxal phosphate
Binding site571Substrate
Binding site641Substrate
Binding site651Pyridoxal phosphate
Binding site991Pyridoxal phosphate
Binding site1211Substrate; via carbonyl oxygen
Binding site1751Pyridoxal phosphate
Binding site2031Pyridoxal phosphate
Binding site2281Pyridoxal phosphate
Binding site2351Pyridoxal phosphate
Binding site2461Substrate
Binding site2631Pyridoxal phosphate; via amide nitrogen and carbonyl oxygen
Binding site3631Pyridoxal phosphate
Site551Transaldimination and stability
Site2351Transaldimination and stability

Amino acid modifications

Modified residue541N6-acetyllysine Ref.14
Modified residue621N6-succinyllysine Ref.16
Modified residue2291N6-(pyridoxal phosphate)lysine HAMAP-Rule MF_00051
Modified residue2421N6-succinyllysine Ref.16
Modified residue2501N6-acetyllysine; alternate Ref.14
Modified residue2501N6-succinyllysine; alternate Ref.16
Modified residue2771N6-succinyllysine Ref.16
Modified residue2851N6-acetyllysine Ref.14
Modified residue2931N6-succinyllysine Ref.16
Modified residue3311N6-succinyllysine Ref.16
Modified residue3461N6-succinyllysine Ref.16
Modified residue3541N6-acetyllysine; alternate Ref.14
Modified residue3541N6-succinyllysine; alternate Ref.16
Modified residue3751N6-acetyllysine Ref.14

Experimental info

Mutagenesis551Y → F: 50 and 15-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 4-fold decrease in the catalytic efficiency. Ref.19
Mutagenesis651Y → F: Decrease in catalytic activity. Ref.17
Mutagenesis851L → 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. Ref.15
Mutagenesis2141P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. Ref.11
Mutagenesis2141P → G: No significant difference in catalytic efficiency and affinity compared to the wild-type. Ref.11
Mutagenesis2161P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. Alteration in the folding rate. Ref.11
Mutagenesis2161P → G: Important decrease in affinity and catalytic efficiency. Severely compromised in folding into a catalytically competent enzyme. Ref.11
Mutagenesis2181P → A: No significant difference in catalytic efficiency and affinity compared to the wild-type. Ref.11
Mutagenesis2181P → G: No significant difference in catalytic efficiency and affinity compared to the wild-type. Ref.11
Mutagenesis2351R → K: 1500- and 20-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 15-fold decrease in the catalytic efficiency. Ref.19
Mutagenesis2351R → L: 450- and 11-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 60-fold decrease in the catalytic efficiency. Ref.19
Mutagenesis2351R → Q: 900- and 17-fold increase in the affinity for serine and tetrahydrofolate, respectively, and 30-fold decrease in the catalytic efficiency. Ref.19
Mutagenesis2581P → A: Important decrease in affinity and catalytic efficiency. Reduced thermal stability. Ref.11
Mutagenesis2581P → G: Important decrease in affinity and catalytic efficiency. Ref.11
Mutagenesis2641P → A: Important decrease in affinity and catalytic efficiency. Ref.11
Mutagenesis2641P → G: Important decrease in affinity and catalytic efficiency. Ref.11
Mutagenesis2761L → 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. Ref.15
Mutagenesis3631R → A: It does not bind serine and glycine and shows no activity with serine as the substrate. Ref.9
Mutagenesis3631R → K: Exhibits only 0.03% of the catalytic activity of the wild-type and a 15-fold reduction in affinity for glycine and serine. Ref.9
Mutagenesis3721R → A: No significant difference compared to the wild-type. Ref.9
Mutagenesis3721R → K: No significant difference compared to the wild-type. Ref.9

Secondary structure

........................................................................ 417
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0A825 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 13E5558E99938539

FASTA41745,317
        10         20         30         40         50         60 
MLKREMNIAD YDAELWQAME QEKVRQEEHI ELIASENYTS PRVMQAQGSQ LTNKYAEGYP 

        70         80         90        100        110        120 
GKRYYGGCEY VDIVEQLAID RAKELFGADY ANVQPHSGSQ ANFAVYTALL EPGDTVLGMN 

       130        140        150        160        170        180 
LAHGGHLTHG SPVNFSGKLY NIVPYGIDAT GHIDYADLEK QAKEHKPKMI IGGFSAYSGV 

       190        200        210        220        230        240 
VDWAKMREIA DSIGAYLFVD MAHVAGLVAA GVYPNPVPHA HVVTTTTHKT LAGPRGGLIL 

       250        260        270        280        290        300 
AKGGSEELYK KLNSAVFPGG QGGPLMHVIA GKAVALKEAM EPEFKTYQQQ VAKNAKAMVE 

       310        320        330        340        350        360 
VFLERGYKVV SGGTDNHLFL VDLVDKNLTG KEADAALGRA NITVNKNSVP NDPKSPFVTS 

       370        380        390        400        410 
GIRVGTPAIT RRGFKEAEAK ELAGWMCDVL DSINDEAVIE RIKGKVLDIC ARYPVYA 

« Hide

References

« Hide 'large scale' references
[1]"Complete nucleotide sequence of the E. coli glyA gene."
Plamann M.D., Stauffer L.T., Urbanowski M.L., Stauffer G.V.
Nucleic Acids Res. 11:2065-2075(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: K12.
[2]"Construction of a contiguous 874-kb sequence of the Escherichia coli-K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features."
Yamamoto Y., Aiba H., Baba T., Hayashi K., Inada T., Isono K., Itoh T., Kimura S., Kitagawa M., Makino K., Miki T., Mitsuhashi N., Mizobuchi K., Mori H., Nakade S., Nakamura Y., Nashimoto H., Oshima T. expand/collapse author list , Oyama S., Saito N., Sampei G., Satoh Y., Sivasundaram S., Tagami H., Takahashi H., Takeda J., Takemoto K., Uehara K., Wada C., Yamagata S., Horiuchi T.
DNA Res. 4:91-113(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
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]"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12."
Link A.J., Robison K., Church G.M.
Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-19.
Strain: K12 / EMG2.
[6]"Isolation and nucleotide sequence of the hmp gene that encodes a haemoglobin-like protein in Escherichia coli K-12."
Vasudevan S.G., Armarego W.L.F., Shaw D.C., Lilley P.E., Dixon N.E., Poole R.K.
Mol. Gen. Genet. 226:49-58(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-17.
Strain: K12.
[7]Pasquali C., Sanchez J.-C., Ravier F., Golaz O., Hughes G.J., Frutiger S., Paquet N., Wilkins M., Appel R.D., Bairoch A., Hochstrasser D.F.
Submitted (SEP-1994) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-11.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[8]"Characterization of the Escherichia coli gene for serine hydroxymethyltransferase."
Plamann M.D., Stauffer G.V.
Gene 22:9-18(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-7, FUNCTION AS A SERINE HYDROXYMETHYLTRANSFERASE.
[9]"The function of arginine 363 as the substrate carboxyl-binding site in Escherichia coli serine hydroxymethyltransferase."
Delle Fratte S., Iurescia S., Angelaccio S., Bossa F., Schirch V.
Eur. J. Biochem. 225:395-401(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-363 AND ARG-372.
[10]"Escherichia coli proteome analysis using the gene-protein database."
VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.
Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY 2D-GEL.
[11]"Role of proline residues in the folding of serine hydroxymethyltransferase."
Fu T.F., Boja E.S., Safo M.K., Schirch V.
J. Biol. Chem. 278:31088-31094(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-214; PRO-216; PRO-218; PRO-258 AND PRO-264, BIOPHYSICOCHEMICAL PROPERTIES.
[12]"CsgD, a regulator of curli and cellulose synthesis, also regulates serine hydroxymethyltransferase synthesis in Escherichia coli K-12."
Chirwa N.T., Herrington M.B.
Microbiology 149:525-535(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[13]"The mechanism of addition of pyridoxal 5'-phosphate to Escherichia coli apo-serine hydroxymethyltransferase."
Malerba F., Bellelli A., Giorgi A., Bossa F., Contestabile R.
Biochem. J. 404:477-485(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REACTION MECHANISMN.
[14]"Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli."
Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F., Grishin N.V., Zhao Y.
Mol. Cell. Proteomics 8:215-225(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-54; LYS-250; LYS-285; LYS-354 AND LYS-375, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: K12 / JW1106 and K12 / MG1655 / ATCC 47076.
[15]"The role of evolutionarily conserved hydrophobic contacts in the quaternary structure stability of Escherichia coli serine hydroxymethyltransferase."
Florio R., Chiaraluce R., Consalvi V., Paiardini A., Catacchio B., Bossa F., Contestabile R.
FEBS J. 276:132-143(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-85 AND LEU-276, SUBUNIT.
[16]"Identification of lysine succinylation as a new post-translational modification."
Zhang Z., Tan M., Xie Z., Dai L., Chen Y., Zhao Y.
Nat. Chem. Biol. 7:58-63(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUCCINYLATION AT LYS-62; LYS-242; LYS-250; LYS-277; LYS-293; LYS-331; LYS-346 AND LYS-354.
Strain: K12.
[17]"Role of tyrosine 65 in the mechanism of serine hydroxymethyltransferase."
Contestabile R., Angelaccio S., Bossa F., Wright H.T., Scarsdale N., Kazanina G., Schirch V.
Biochemistry 39:7492-7500(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS AND PYRIDOXAL PHOSPHATE, MUTAGENESIS OF TYR-65.
[18]"Crystal structure at 2.4-A resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate."
Scarsdale J.N., Radaev S., Kazanina G., Schirch V., Wright H.T.
J. Mol. Biol. 296:155-168(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS, SUBUNIT.
[19]"Role of a conserved active site cation-pi interaction in Escherichia coli serine hydroxymethyltransferase."
Vivoli M., Angelucci F., Ilari A., Morea V., Angelaccio S., di Salvo M.L., Contestabile R.
Biochemistry 48:12034-12046(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF MUTANT PHE-55 IN COMPLEX WITH PYRIDOXAL PHOSPHATE, MUTAGENESIS OF TYR-55 AND ARG-235, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V00283 Genomic DNA. Translation: CAA23547.1.
U00096 Genomic DNA. Translation: AAC75604.1.
AP009048 Genomic DNA. Translation: BAA16459.1.
J01620 Genomic DNA. Translation: AAA23912.1.
PIRXYECS. A00559.
RefSeqNP_417046.1. NC_000913.3.
YP_490779.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DFOX-ray2.40A/B/C/D1-417[»]
1EQBX-ray2.70A/B/C/D1-417[»]
3G8MX-ray3.30A1-417[»]
ProteinModelPortalP0A825.
SMRP0A825. Positions 1-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-36205N.
IntActP0A825. 7 interactions.
MINTMINT-7293373.
STRING511145.b2551.

2D gel databases

SWISS-2DPAGEP0A825.

Proteomic databases

PaxDbP0A825.
PRIDEP0A825.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC75604; AAC75604; b2551.
BAA16459; BAA16459; BAA16459.
GeneID12932320.
947022.
KEGGecj:Y75_p2504.
eco:b2551.
PATRIC32120501. VBIEscCol129921_2653.

Organism-specific databases

EchoBASEEB0403.
EcoGeneEG10408. glyA.

Phylogenomic databases

eggNOGCOG0112.
HOGENOMHOG000239404.
KOK00600.
OMAKEMYDLE.
OrthoDBEOG6Z0QB2.
PhylomeDBP0A825.
ProtClustDBPRK00011.

Enzyme and pathway databases

BioCycEcoCyc:GLYOHMETRANS-MONOMER.
ECOL316407:JW2535-MONOMER.
MetaCyc:GLYOHMETRANS-MONOMER.
UniPathwayUPA00193.
UPA00288; UER01023.

Gene expression databases

GenevestigatorP0A825.

Family and domain databases

Gene3D3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
HAMAPMF_00051. SHMT.
InterProIPR015424. 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]
PANTHERPTHR11680. PTHR11680. 1 hit.
PfamPF00464. SHMT. 1 hit.
[Graphical view]
PIRSFPIRSF000412. SHMT. 1 hit.
SUPFAMSSF53383. SSF53383. 1 hit.
PROSITEPS00096. SHMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP0A825.
PROP0A825.

Entry information

Entry nameGLYA_ECOLI
AccessionPrimary (citable) accession number: P0A825
Secondary accession number(s): P00477
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene