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Protein

Thymidylate synthase

Gene

thyA

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

Functioni

Catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor and reductant in the reaction, yielding dihydrofolate (DHF) as a by-product (PubMed:3286637, PubMed:2223754, PubMed:9826509). This enzymatic reaction provides an intracellular de novo source of dTMP, an essential precursor for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation (PubMed:7708505).4 Publications

Catalytic activityi

5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.UniRule annotation3 Publications

Kineticsi

kcat is 8.8 sec(-1).1 Publication

Manual assertion based on experiment ini

  1. KM=50 µM for dUMP1 Publication
  2. KM=25 µM for 5,10-methylenetetrahydrofolate1 Publication
  3. KM=4.1 µM for dUMP1 Publication
  4. KM=13.6 µM for 5,10-methylenetetrahydrofolate1 Publication
  1. Vmax=5.47 µmol/min/mg enzyme1 Publication

Pathwayi: dTTP biosynthesis

This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.UniRule annotation
View all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei21dUMPCombined sources2 Publications1
Binding sitei515,10-methylenetetrahydrofolateCombined sources1 Publication1
Active sitei146NucleophileUniRule annotation3 Publications1
Binding sitei1695,10-methylenetetrahydrofolateCombined sources1 Publication1
Binding sitei177dUMPCombined sources2 Publications1
Binding sitei2635,10-methylenetetrahydrofolate; via carbonyl oxygenCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi126 – 127dUMP; shared with dimeric partnerCombined sources2 Publications2
Nucleotide bindingi166 – 169dUMPCombined sources2 Publications4
Nucleotide bindingi207 – 209dUMPCombined sources2 Publications3

GO - Molecular functioni

  • RNA binding Source: UniProtKB-KW
  • thymidylate synthase activity Source: EcoCyc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Nucleotide biosynthesis, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciEcoCyc:THYMIDYLATESYN-MONOMER.
ECOL316407:JW2795-MONOMER.
MetaCyc:THYMIDYLATESYN-MONOMER.
BRENDAi2.1.1.45. 2026.
SABIO-RKP0A884.
UniPathwayiUPA00575.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidylate synthase3 PublicationsUniRule annotation (EC:2.1.1.45UniRule annotation3 Publications)
Short name:
TS3 PublicationsUniRule annotation
Short name:
TSaseUniRule annotation
Gene namesi
Name:thyA1 PublicationUniRule annotation
Ordered Locus Names:b2827, JW2795
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG11002. thyA.

Subcellular locationi

  • Cytoplasm UniRule annotation

GO - Cellular componenti

  • cytosol Source: EcoCyc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi50C → Y: Shows 0.2% of wild-type catalytic activity, but substrate affinity is not affected. 1 Publication1
Mutagenesisi126R → E: Shows 2000-fold decrease in catalytic activity and 600-fold decrease in affinity for dUMP. 1 Publication1
Mutagenesisi177N → A: Shows 200-fold decrease in catalytic activity, 20-fold decrease in affinity for dUMP, and 10-fold decrease in affinity for mTHF. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2555.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001409541 – 264Thymidylate synthaseAdd BLAST264

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-formylmethionineCurated1

Post-translational modificationi

Although not discussed in the published references, Met-1 is represented in the submitted PDB entries as being modified by either a formyl, or a carboxyl group. The N-terminal is probably N-(dihydroxymethyl)methionine, the hydrated form of N-formylmethionine.

Keywords - PTMi

Formylation

Proteomic databases

EPDiP0A884.
PaxDbiP0A884.
PRIDEiP0A884.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi4262058. 195 interactors.
DIPiDIP-48261N.
IntActiP0A884. 5 interactors.
MINTiMINT-1265510.
STRINGi511145.b2827.

Chemistry databases

BindingDBiP0A884.

Structurei

Secondary structure

1264
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 14Combined sources13
Beta strandi16 – 18Combined sources3
Beta strandi21 – 23Combined sources3
Beta strandi26 – 37Combined sources12
Helixi38 – 40Combined sources3
Beta strandi46 – 48Combined sources3
Helixi52 – 64Combined sources13
Helixi70 – 74Combined sources5
Helixi81 – 83Combined sources3
Helixi94 – 100Combined sources7
Beta strandi101 – 103Combined sources3
Turni104 – 106Combined sources3
Beta strandi107 – 109Combined sources3
Helixi111 – 121Combined sources11
Beta strandi129 – 131Combined sources3
Helixi135 – 140Combined sources6
Beta strandi141 – 143Combined sources3
Beta strandi146 – 155Combined sources10
Beta strandi158 – 169Combined sources12
Turni170 – 173Combined sources4
Helixi174 – 191Combined sources18
Beta strandi195 – 209Combined sources15
Helixi210 – 212Combined sources3
Helixi213 – 220Combined sources8
Beta strandi229 – 232Combined sources4
Helixi239 – 241Combined sources3
Helixi244 – 246Combined sources3
Beta strandi247 – 251Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AIQX-ray2.20A/B1-264[»]
1AJMX-ray2.40A1-264[»]
1AN5X-ray2.60A/B1-264[»]
1AOBX-ray2.10A1-264[»]
1AXWX-ray1.70A/B1-264[»]
1BDUX-ray2.10A1-264[»]
1BIDX-ray2.20A1-264[»]
1BJGX-ray2.30A1-264[»]
1BQ1X-ray2.50A/B1-264[»]
1BQ2X-ray2.20A1-264[»]
1DDUX-ray2.10A/B1-264[»]
1DNAX-ray2.20A/B1-264[»]
1EV5X-ray1.70A1-264[»]
1EV8X-ray2.60A1-264[»]
1EVFX-ray1.70A1-264[»]
1EVGX-ray2.00A1-264[»]
1F4BX-ray1.75A1-264[»]
1F4CX-ray2.00A/B1-264[»]
1F4DX-ray2.15A/B1-264[»]
1F4EX-ray1.90A1-264[»]
1F4FX-ray2.00A/B1-264[»]
1F4GX-ray1.75A/B1-264[»]
1FFLX-ray2.94A1-264[»]
1FWMX-ray2.20A/B1-264[»]
1JG0X-ray2.00A/B1-264[»]
1JTQX-ray2.50A/B1-264[»]
1JTUX-ray2.20A/B1-264[»]
1JUTX-ray2.70A/B1-264[»]
1KCEX-ray2.00A/B1-264[»]
1KZIX-ray1.75A/B1-264[»]
1KZJX-ray2.60A/B/C/D/E/F1-264[»]
1NCEX-ray2.40A/B1-264[»]
1QQQX-ray1.50A1-264[»]
1SYNX-ray2.00A/B1-264[»]
1TDUX-ray2.10A/B1-264[»]
1TJSX-ray2.20A1-264[»]
1TLCX-ray2.10A/B1-264[»]
1TLSX-ray2.60A/B1-264[»]
1TRGX-ray1.90A1-264[»]
1TSDX-ray1.95A/B1-264[»]
1TSNX-ray2.20A1-264[»]
1TYSX-ray1.80A1-264[»]
1ZPRX-ray2.50A/B1-264[»]
2A9WX-ray1.65A/B/C/D1-264[»]
2BBQX-ray2.30A/B1-264[»]
2FTNX-ray1.60A1-264[»]
2FTOX-ray2.00X1-264[»]
2FTQX-ray1.81A1-264[»]
2G8XX-ray1.83A/B1-264[»]
2KCEX-ray2.20A/B1-264[»]
2TSCX-ray1.97A/B1-264[»]
2VETX-ray2.20A1-264[»]
2VF0X-ray3.00A/B1-264[»]
3B5BX-ray2.70A/B1-264[»]
3B9HX-ray2.49A1-264[»]
3BFIX-ray2.20A1-264[»]
3BGXX-ray1.93A1-264[»]
3BHLX-ray1.40A/B1-264[»]
3BHRX-ray1.90A1-264[»]
3TMSX-ray2.10A1-264[»]
4F2VX-ray2.49A/B1-264[»]
4GEVX-ray1.30A/B1-264[»]
4ISKX-ray1.75A/B/C/D/E/F/G/H2-264[»]
4KNZX-ray1.30A/B1-264[»]
ProteinModelPortaliP0A884.
SMRiP0A884.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0A884.

Family & Domainsi

Sequence similaritiesi

Belongs to the thymidylate synthase family. Bacterial-type ThyA subfamily.UniRule annotation

Phylogenomic databases

eggNOGiENOG4105C0V. Bacteria.
COG0207. LUCA.
HOGENOMiHOG000257900.
InParanoidiP0A884.
KOiK00560.
OMAiIVYELLW.
PhylomeDBiP0A884.

Family and domain databases

CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
InterProiIPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 2 hits.
PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0A884-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKQYLELMQK VLDEGTQKND RTGTGTLSIF GHQMRFNLQD GFPLVTTKRC
60 70 80 90 100
HLRSIIHELL WFLQGDTNIA YLHENNVTIW DEWADENGDL GPVYGKQWRA
110 120 130 140 150
WPTPDGRHID QITTVLNQLK NDPDSRRIIV SAWNVGELDK MALAPCHAFF
160 170 180 190 200
QFYVADGKLS CQLYQRSCDV FLGLPFNIAS YALLVHMMAQ QCDLEVGDFV
210 220 230 240 250
WTGGDTHLYS NHMDQTHLQL SREPRPLPKL IIKRKPESIF DYRFEDFEIE
260
GYDPHPGIKA PVAI
Length:264
Mass (Da):30,480
Last modified:July 21, 1986 - v1
Checksum:i0E6D88ED98D24D22
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01710 Genomic DNA. Translation: AAA24675.1.
U29581 Genomic DNA. Translation: AAB40474.1.
U00096 Genomic DNA. Translation: AAC75866.1.
AP009048 Genomic DNA. Translation: BAE76896.1.
X03966 Genomic DNA. Translation: CAA27600.1.
PIRiA00549. SYECT.
RefSeqiNP_417304.1. NC_000913.3.
WP_000816232.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC75866; AAC75866; b2827.
BAE76896; BAE76896; BAE76896.
GeneIDi949035.
KEGGiecj:JW2795.
eco:b2827.
PATRICi32121072. VBIEscCol129921_2925.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01710 Genomic DNA. Translation: AAA24675.1.
U29581 Genomic DNA. Translation: AAB40474.1.
U00096 Genomic DNA. Translation: AAC75866.1.
AP009048 Genomic DNA. Translation: BAE76896.1.
X03966 Genomic DNA. Translation: CAA27600.1.
PIRiA00549. SYECT.
RefSeqiNP_417304.1. NC_000913.3.
WP_000816232.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AIQX-ray2.20A/B1-264[»]
1AJMX-ray2.40A1-264[»]
1AN5X-ray2.60A/B1-264[»]
1AOBX-ray2.10A1-264[»]
1AXWX-ray1.70A/B1-264[»]
1BDUX-ray2.10A1-264[»]
1BIDX-ray2.20A1-264[»]
1BJGX-ray2.30A1-264[»]
1BQ1X-ray2.50A/B1-264[»]
1BQ2X-ray2.20A1-264[»]
1DDUX-ray2.10A/B1-264[»]
1DNAX-ray2.20A/B1-264[»]
1EV5X-ray1.70A1-264[»]
1EV8X-ray2.60A1-264[»]
1EVFX-ray1.70A1-264[»]
1EVGX-ray2.00A1-264[»]
1F4BX-ray1.75A1-264[»]
1F4CX-ray2.00A/B1-264[»]
1F4DX-ray2.15A/B1-264[»]
1F4EX-ray1.90A1-264[»]
1F4FX-ray2.00A/B1-264[»]
1F4GX-ray1.75A/B1-264[»]
1FFLX-ray2.94A1-264[»]
1FWMX-ray2.20A/B1-264[»]
1JG0X-ray2.00A/B1-264[»]
1JTQX-ray2.50A/B1-264[»]
1JTUX-ray2.20A/B1-264[»]
1JUTX-ray2.70A/B1-264[»]
1KCEX-ray2.00A/B1-264[»]
1KZIX-ray1.75A/B1-264[»]
1KZJX-ray2.60A/B/C/D/E/F1-264[»]
1NCEX-ray2.40A/B1-264[»]
1QQQX-ray1.50A1-264[»]
1SYNX-ray2.00A/B1-264[»]
1TDUX-ray2.10A/B1-264[»]
1TJSX-ray2.20A1-264[»]
1TLCX-ray2.10A/B1-264[»]
1TLSX-ray2.60A/B1-264[»]
1TRGX-ray1.90A1-264[»]
1TSDX-ray1.95A/B1-264[»]
1TSNX-ray2.20A1-264[»]
1TYSX-ray1.80A1-264[»]
1ZPRX-ray2.50A/B1-264[»]
2A9WX-ray1.65A/B/C/D1-264[»]
2BBQX-ray2.30A/B1-264[»]
2FTNX-ray1.60A1-264[»]
2FTOX-ray2.00X1-264[»]
2FTQX-ray1.81A1-264[»]
2G8XX-ray1.83A/B1-264[»]
2KCEX-ray2.20A/B1-264[»]
2TSCX-ray1.97A/B1-264[»]
2VETX-ray2.20A1-264[»]
2VF0X-ray3.00A/B1-264[»]
3B5BX-ray2.70A/B1-264[»]
3B9HX-ray2.49A1-264[»]
3BFIX-ray2.20A1-264[»]
3BGXX-ray1.93A1-264[»]
3BHLX-ray1.40A/B1-264[»]
3BHRX-ray1.90A1-264[»]
3TMSX-ray2.10A1-264[»]
4F2VX-ray2.49A/B1-264[»]
4GEVX-ray1.30A/B1-264[»]
4ISKX-ray1.75A/B/C/D/E/F/G/H2-264[»]
4KNZX-ray1.30A/B1-264[»]
ProteinModelPortaliP0A884.
SMRiP0A884.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262058. 195 interactors.
DIPiDIP-48261N.
IntActiP0A884. 5 interactors.
MINTiMINT-1265510.
STRINGi511145.b2827.

Chemistry databases

BindingDBiP0A884.
ChEMBLiCHEMBL2555.

Proteomic databases

EPDiP0A884.
PaxDbiP0A884.
PRIDEiP0A884.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75866; AAC75866; b2827.
BAE76896; BAE76896; BAE76896.
GeneIDi949035.
KEGGiecj:JW2795.
eco:b2827.
PATRICi32121072. VBIEscCol129921_2925.

Organism-specific databases

EchoBASEiEB0995.
EcoGeneiEG11002. thyA.

Phylogenomic databases

eggNOGiENOG4105C0V. Bacteria.
COG0207. LUCA.
HOGENOMiHOG000257900.
InParanoidiP0A884.
KOiK00560.
OMAiIVYELLW.
PhylomeDBiP0A884.

Enzyme and pathway databases

UniPathwayiUPA00575.
BioCyciEcoCyc:THYMIDYLATESYN-MONOMER.
ECOL316407:JW2795-MONOMER.
MetaCyc:THYMIDYLATESYN-MONOMER.
BRENDAi2.1.1.45. 2026.
SABIO-RKP0A884.

Miscellaneous databases

EvolutionaryTraceiP0A884.
PROiP0A884.

Family and domain databases

CDDicd00351. TS_Pyrimidine_HMase. 1 hit.
Gene3Di3.30.572.10. 1 hit.
HAMAPiMF_00008. Thymidy_synth_bact. 1 hit.
InterProiIPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]
PfamiPF00303. Thymidylat_synt. 1 hit.
[Graphical view]
PRINTSiPR00108. THYMDSNTHASE.
SUPFAMiSSF55831. SSF55831. 1 hit.
TIGRFAMsiTIGR03284. thym_sym. 2 hits.
PROSITEiPS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTYSY_ECOLI
AccessioniPrimary (citable) accession number: P0A884
Secondary accession number(s): P00470, Q2MA10
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 107 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.