UniProtKB - P0A884 (TYSY_ECOLI)
Protein
Thymidylate synthase
Gene
thyA
Organism
Escherichia coli (strain K12)
Status
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
- (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-dihydrofolate + dTMPUniRule annotation3 PublicationsEC:2.1.1.45UniRule annotation3 Publications
Kineticsi
kcat is 8.8 sec(-1).1 Publication
- KM=50 µM for dUMP1 Publication
- KM=25 µM for 5,10-methylenetetrahydrofolate1 Publication
- KM=4.1 µM for dUMP1 Publication
- KM=13.6 µM for 5,10-methylenetetrahydrofolate1 Publication
- Vmax=5.47 µmol/min/mg enzyme1 Publication
: dTTP biosynthesis Pathwayi
This protein is involved in the pathway dTTP biosynthesis, which is part of Pyrimidine metabolism.UniRule annotationView all proteins of this organism that are known to be involved in the pathway dTTP biosynthesis and in Pyrimidine metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 21 | dUMPCombined sources2 Publications | 1 | |
Binding sitei | 51 | 5,10-methylenetetrahydrofolateCombined sources1 Publication | 1 | |
Active sitei | 146 | NucleophileUniRule annotation3 Publications | 1 | |
Binding sitei | 169 | 5,10-methylenetetrahydrofolateCombined sources1 Publication | 1 | |
Binding sitei | 177 | dUMPCombined sources2 Publications | 1 | |
Binding sitei | 263 | 5,10-methylenetetrahydrofolate; via carbonyl oxygenCombined sources1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 126 – 127 | dUMP; shared with dimeric partnerCombined sources2 Publications | 2 | |
Nucleotide bindingi | 166 – 169 | dUMPCombined sources2 Publications | 4 | |
Nucleotide bindingi | 207 – 209 | dUMPCombined sources2 Publications | 3 |
GO - Molecular functioni
- magnesium ion binding Source: EcoCyc
- RNA binding Source: UniProtKB-KW
- thymidylate synthase activity Source: EcoCyc
GO - Biological processi
- dTMP biosynthetic process Source: EcoCyc
- dTTP biosynthetic process Source: UniProtKB-UniPathway
- methylation Source: UniProtKB-KW
- regulation of translation Source: UniProtKB-KW
- response to radiation Source: EcoCyc
Keywordsi
Molecular function | Methyltransferase, Repressor, RNA-binding, Transferase |
Biological process | Nucleotide biosynthesis, Translation regulation |
Enzyme and pathway databases
BioCyci | EcoCyc:THYMIDYLATESYN-MONOMER MetaCyc:THYMIDYLATESYN-MONOMER |
BRENDAi | 2.1.1.45, 2026 |
SABIO-RKi | P0A884 |
UniPathwayi | UPA00575 |
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 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
- Cytoplasm UniRule annotation
GO - Cellular componenti
- cytosol Source: EcoCyc
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 50 | C → Y: Shows 0.2% of wild-type catalytic activity, but substrate affinity is not affected. 1 Publication | 1 | |
Mutagenesisi | 126 | R → E: Shows 2000-fold decrease in catalytic activity and 600-fold decrease in affinity for dUMP. 1 Publication | 1 | |
Mutagenesisi | 177 | N → A: Shows 200-fold decrease in catalytic activity, 20-fold decrease in affinity for dUMP, and 10-fold decrease in affinity for mTHF. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL2555 |
DrugBanki | DB02031, (6S)-5,6,7,8-tetrahydrofolic acid DB04447, 1,4-Dithiothreitol DB03541, 10-Propargyl-5,8-Dideazafolic Acid DB03274, 2',5'-Dideoxyuridine DB04457, 2'-Deoxyguanosine-5'-Monophosphate DB02256, 2'-Deoxyuridine DB08131, 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACID DB04696, 4-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEIN DB02301, 5,10-Methylene-6-Hydrofolic Acid DB03761, 5-fluoro-2'-deoxyuridine-5'-monophosphate DB03800, Deoxyuridine monophosphate DB02467, L-methionine (S)-S-oxide DB02223, LY231514 tetra glu DB03038, LY341770 DB03157, N,O-Didansyl-L-Tyrosine DB03818, N-[Tosyl-D-Prolinyl]Amino-Ethanethiol DB02899, N-Carboxymethionine DB04586, o-Bromophenol DB04530, S,S-(2-Hydroxyethyl)Thiocysteine DB04503, Sp-722 DB03558, SP-876 DB02752, Tosyl-D-Proline |
DrugCentrali | P0A884 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000140954 | 1 – 264 | Thymidylate synthaseAdd BLAST | 264 |
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
FormylationProteomic databases
jPOSTi | P0A884 |
PaxDbi | P0A884 |
PRIDEi | P0A884 |
Interactioni
Subunit structurei
Homodimer.
2 PublicationsProtein-protein interaction databases
BioGRIDi | 4262058, 217 interactors |
DIPi | DIP-48261N |
IntActi | P0A884, 5 interactors |
STRINGi | 511145.b2827 |
Chemistry databases
BindingDBi | P0A884 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P0A884 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0A884 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | COG0207, Bacteria |
HOGENOMi | CLU_021669_0_0_6 |
InParanoidi | P0A884 |
PhylomeDBi | P0A884 |
Family and domain databases
CDDi | cd00351, TS_Pyrimidine_HMase, 1 hit |
Gene3Di | 3.30.572.10, 1 hit |
HAMAPi | MF_00008, Thymidy_synth_bact, 1 hit |
InterProi | View protein in InterPro IPR023451, Thymidate_synth/dCMP_Mease IPR036926, Thymidate_synth/dCMP_Mease_sf IPR000398, Thymidylate_synthase IPR020940, Thymidylate_synthase_AS |
Pfami | View protein in Pfam PF00303, Thymidylat_synt, 1 hit |
PRINTSi | PR00108, THYMDSNTHASE |
SUPFAMi | SSF55831, SSF55831, 1 hit |
TIGRFAMsi | TIGR03284, thym_sym, 2 hits |
PROSITEi | View protein in PROSITE PS00091, THYMIDYLATE_SYNTHASE, 1 hit |
i Sequence
Sequence statusi: Complete.
P0A884-1 [UniParc]FASTAAdd to basket
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
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 |
PIRi | A00549, SYECT |
RefSeqi | NP_417304.1, NC_000913.3 WP_000816232.1, NZ_STEB01000034.1 |
Genome annotation databases
EnsemblBacteriai | AAC75866; AAC75866; b2827 BAE76896; BAE76896; BAE76896 |
GeneIDi | 58461970 949035 |
KEGGi | ecj:JW2795 eco:b2827 |
PATRICi | fig|1411691.4.peg.3908 |
Similar proteinsi
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 |
PIRi | A00549, SYECT |
RefSeqi | NP_417304.1, NC_000913.3 WP_000816232.1, NZ_STEB01000034.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1AIQ | X-ray | 2.20 | A/B | 1-264 | [»] | |
1AJM | X-ray | 2.40 | A | 1-264 | [»] | |
1AN5 | X-ray | 2.60 | A/B | 1-264 | [»] | |
1AOB | X-ray | 2.10 | A | 1-264 | [»] | |
1AXW | X-ray | 1.70 | A/B | 1-264 | [»] | |
1BDU | X-ray | 2.10 | A | 1-264 | [»] | |
1BID | X-ray | 2.20 | A | 1-264 | [»] | |
1BJG | X-ray | 2.30 | A | 1-264 | [»] | |
1BQ1 | X-ray | 2.50 | A/B | 1-264 | [»] | |
1BQ2 | X-ray | 2.20 | A | 1-264 | [»] | |
1DDU | X-ray | 2.10 | A/B | 1-264 | [»] | |
1DNA | X-ray | 2.20 | A/B | 1-264 | [»] | |
1EV5 | X-ray | 1.70 | A | 1-264 | [»] | |
1EV8 | X-ray | 2.60 | A | 1-264 | [»] | |
1EVF | X-ray | 1.70 | A | 1-264 | [»] | |
1EVG | X-ray | 2.00 | A | 1-264 | [»] | |
1F4B | X-ray | 1.75 | A | 1-264 | [»] | |
1F4C | X-ray | 2.00 | A/B | 1-264 | [»] | |
1F4D | X-ray | 2.15 | A/B | 1-264 | [»] | |
1F4E | X-ray | 1.90 | A | 1-264 | [»] | |
1F4F | X-ray | 2.00 | A/B | 1-264 | [»] | |
1F4G | X-ray | 1.75 | A/B | 1-264 | [»] | |
1FFL | X-ray | 2.94 | A | 1-264 | [»] | |
1FWM | X-ray | 2.20 | A/B | 1-264 | [»] | |
1JG0 | X-ray | 2.00 | A/B | 1-264 | [»] | |
1JTQ | X-ray | 2.50 | A/B | 1-264 | [»] | |
1JTU | X-ray | 2.20 | A/B | 1-264 | [»] | |
1JUT | X-ray | 2.70 | A/B | 1-264 | [»] | |
1KCE | X-ray | 2.00 | A/B | 1-264 | [»] | |
1KZI | X-ray | 1.75 | A/B | 1-264 | [»] | |
1KZJ | X-ray | 2.60 | A/B/C/D/E/F | 1-264 | [»] | |
1NCE | X-ray | 2.40 | A/B | 1-264 | [»] | |
1QQQ | X-ray | 1.50 | A | 1-264 | [»] | |
1SYN | X-ray | 2.00 | A/B | 1-264 | [»] | |
1TDU | X-ray | 2.10 | A/B | 1-264 | [»] | |
1TJS | X-ray | 2.20 | A | 1-264 | [»] | |
1TLC | X-ray | 2.10 | A/B | 1-264 | [»] | |
1TLS | X-ray | 2.60 | A/B | 1-264 | [»] | |
1TRG | X-ray | 1.90 | A | 1-264 | [»] | |
1TSD | X-ray | 1.95 | A/B | 1-264 | [»] | |
1TSN | X-ray | 2.20 | A | 1-264 | [»] | |
1TYS | X-ray | 1.80 | A | 1-264 | [»] | |
1ZPR | X-ray | 2.50 | A/B | 1-264 | [»] | |
2A9W | X-ray | 1.65 | A/B/C/D | 1-264 | [»] | |
2BBQ | X-ray | 2.30 | A/B | 1-264 | [»] | |
2FTN | X-ray | 1.60 | A | 1-264 | [»] | |
2FTO | X-ray | 2.00 | X | 1-264 | [»] | |
2FTQ | X-ray | 1.81 | A | 1-264 | [»] | |
2G8X | X-ray | 1.83 | A/B | 1-264 | [»] | |
2KCE | X-ray | 2.20 | A/B | 1-264 | [»] | |
2TSC | X-ray | 1.97 | A/B | 1-264 | [»] | |
2VET | X-ray | 2.20 | A | 1-264 | [»] | |
2VF0 | X-ray | 3.00 | A/B | 1-264 | [»] | |
3B5B | X-ray | 2.70 | A/B | 1-264 | [»] | |
3B9H | X-ray | 2.49 | A | 1-264 | [»] | |
3BFI | X-ray | 2.20 | A | 1-264 | [»] | |
3BGX | X-ray | 1.93 | A | 1-264 | [»] | |
3BHL | X-ray | 1.40 | A/B | 1-264 | [»] | |
3BHR | X-ray | 1.90 | A | 1-264 | [»] | |
3TMS | X-ray | 2.10 | A | 1-264 | [»] | |
4F2V | X-ray | 2.49 | A/B | 1-264 | [»] | |
4GEV | X-ray | 1.30 | A/B | 1-264 | [»] | |
4ISK | X-ray | 1.75 | A/B/C/D/E/F/G/H | 2-264 | [»] | |
6CDZ | X-ray | 2.40 | A/B | 1-263 | [»] | |
6NNR | X-ray | 1.05 | A/B | 1-264 | [»] | |
SMRi | P0A884 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262058, 217 interactors |
DIPi | DIP-48261N |
IntActi | P0A884, 5 interactors |
STRINGi | 511145.b2827 |
Chemistry databases
BindingDBi | P0A884 |
ChEMBLi | CHEMBL2555 |
DrugBanki | DB02031, (6S)-5,6,7,8-tetrahydrofolic acid DB04447, 1,4-Dithiothreitol DB03541, 10-Propargyl-5,8-Dideazafolic Acid DB03274, 2',5'-Dideoxyuridine DB04457, 2'-Deoxyguanosine-5'-Monophosphate DB02256, 2'-Deoxyuridine DB08131, 2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-3-METHYL-BUTYRIC ACID DB04696, 4-CHLORO-3',3''-DIBROMOPHENOL-1,8-NAPHTHALEIN DB02301, 5,10-Methylene-6-Hydrofolic Acid DB03761, 5-fluoro-2'-deoxyuridine-5'-monophosphate DB03800, Deoxyuridine monophosphate DB02467, L-methionine (S)-S-oxide DB02223, LY231514 tetra glu DB03038, LY341770 DB03157, N,O-Didansyl-L-Tyrosine DB03818, N-[Tosyl-D-Prolinyl]Amino-Ethanethiol DB02899, N-Carboxymethionine DB04586, o-Bromophenol DB04530, S,S-(2-Hydroxyethyl)Thiocysteine DB04503, Sp-722 DB03558, SP-876 DB02752, Tosyl-D-Proline |
DrugCentrali | P0A884 |
Proteomic databases
jPOSTi | P0A884 |
PaxDbi | P0A884 |
PRIDEi | P0A884 |
Genome annotation databases
EnsemblBacteriai | AAC75866; AAC75866; b2827 BAE76896; BAE76896; BAE76896 |
GeneIDi | 58461970 949035 |
KEGGi | ecj:JW2795 eco:b2827 |
PATRICi | fig|1411691.4.peg.3908 |
Organism-specific databases
EchoBASEi | EB0995 |
Phylogenomic databases
eggNOGi | COG0207, Bacteria |
HOGENOMi | CLU_021669_0_0_6 |
InParanoidi | P0A884 |
PhylomeDBi | P0A884 |
Enzyme and pathway databases
UniPathwayi | UPA00575 |
BioCyci | EcoCyc:THYMIDYLATESYN-MONOMER MetaCyc:THYMIDYLATESYN-MONOMER |
BRENDAi | 2.1.1.45, 2026 |
SABIO-RKi | P0A884 |
Miscellaneous databases
EvolutionaryTracei | P0A884 |
PROi | PR:P0A884 |
Family and domain databases
CDDi | cd00351, TS_Pyrimidine_HMase, 1 hit |
Gene3Di | 3.30.572.10, 1 hit |
HAMAPi | MF_00008, Thymidy_synth_bact, 1 hit |
InterProi | View protein in InterPro IPR023451, Thymidate_synth/dCMP_Mease IPR036926, Thymidate_synth/dCMP_Mease_sf IPR000398, Thymidylate_synthase IPR020940, Thymidylate_synthase_AS |
Pfami | View protein in Pfam PF00303, Thymidylat_synt, 1 hit |
PRINTSi | PR00108, THYMDSNTHASE |
SUPFAMi | SSF55831, SSF55831, 1 hit |
TIGRFAMsi | TIGR03284, thym_sym, 2 hits |
PROSITEi | View protein in PROSITE PS00091, THYMIDYLATE_SYNTHASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TYSY_ECOLI | |
Accessioni | P0A884Primary (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: | February 10, 2021 | |
This is version 135 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families