Reviewed, UniProtKB/Swiss-Prot P0A884 (TYSY_ECOLI)

Names and origin

Protein names

Recommended name:
    Thymidylate synthase
      Short name=TS
      Short name=TSase
    EC=2.1.1.45

Gene names

Name:	thyA
Ordered Locus Names:	b2827, JW2795

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	264 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
Catalytic activity	5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP.
Pathway	Pyrimidine metabolism; dTTP biosynthesis.
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Post-translational modification	The N-terminus is carboxylated.
Sequence similarities	Belongs to the thymidylate synthase family.

Ontologies

Keywords
Biological process	Nucleotide biosynthesis Translation regulation
Cellular component	Cytoplasm
Ligand	RNA-binding
Molecular function	Methyltransferase Repressor Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	dTMP biosynthetic process Inferred from electronic annotation. Source: HAMAP
Cellular component	cytoplasm Inferred from electronic annotation. Source: HAMAP
Molecular function	thymidylate synthase activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 264

264

Thymidylate synthase

Sites

Active site

146

1

Secondary structure

1

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264

Helix Strand Turn

Details...

Helix

2 – 14

13

Beta strand

16 – 18

3

Beta strand

26 – 37

12

Helix

38 – 40

3

Helix

52 – 64

13

Helix

70 – 74

5

Helix

81 – 83

3

Helix

94 – 100

7

Helix

111 – 121

11

Beta strand

129 – 131

3

Helix

135 – 140

6

Beta strand

141 – 143

3

Beta strand

146 – 155

10

Beta strand

158 – 169

12

Turn

170 – 173

4

Helix

174 – 191

18

Beta strand

195 – 209

15

Helix

210 – 212

3

Helix

213 – 220

8

Beta strand

229 – 232

4

Helix

244 – 246

3

Beta strand

247 – 251

5

Sequences

	Sequence		Length	Mass (Da)
	P0A884-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 0E6D88ED98D24D22	FASTA	264	30,480
	10 20 30 40 50 60 MKQYLELMQK VLDEGTQKND RTGTGTLSIF GHQMRFNLQD GFPLVTTKRC HLRSIIHELL 70 80 90 100 110 120 WFLQGDTNIA YLHENNVTIW DEWADENGDL GPVYGKQWRA WPTPDGRHID QITTVLNQLK 130 140 150 160 170 180 NDPDSRRIIV SAWNVGELDK MALAPCHAFF QFYVADGKLS CQLYQRSCDV FLGLPFNIAS 190 200 210 220 230 240 YALLVHMMAQ QCDLEVGDFV WTGGDTHLYS NHMDQTHLQL SREPRPLPKL IIKRKPESIF 250 260 DYRFEDFEIE GYDPHPGIKA PVAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the Escherichia coli thyA gene and its thymidylate synthase product." Belfort M., Maley G.F., Pedersen-Lane J., Maley F. Proc. Natl. Acad. Sci. U.S.A. 80:4914-4918(1983) [PubMed: 6308660] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE. Strain: K12 / JM103 / ATCC 39403 / DSM 2829 / NCIB 12044.
[2]	"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 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"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: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[4]	"Complete nucleotide sequence of the Escherichia coli recC gene and of the thyA-recC intergenic region." Finch P.W., Wilson R.E., Brown K., Hickson I.D., Tomkinson A.E., Emmerson P.T. Nucleic Acids Res. 14:4437-4451(1986) [PubMed: 3520484] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 63-264.
[5]	"Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate." Montfort W.R., Perry K.M., Fauman E.B., Finer-Moore J.S., Maley G.F., Hardy L., Maley F., Stroud R.M. Biochemistry 29:6964-6977(1990) [PubMed: 2223754] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS).
[6]	"Characterization of a specific interaction between Escherichia coli thymidylate synthase and Escherichia coli thymidylate synthase mRNA." Voeller D.M., Changchien L.-M., Maley G.F., Maley F., Takechi T., Turner R.E., Montfort W.R., Allegra C.J., Chu E. Nucleic Acids Res. 23:869-875(1995) [PubMed: 7708505] [Abstract] Cited for: MECHANISM OF TRANSLATION REGULATION.
[7]	"Amino acid substitution analysis of E. coli thymidylate synthase: the study of a highly conserved region at the N-terminus." Kim C.W., Michaels M.L., Miller J.F. Proteins 13:352-363(1992) [PubMed: 1518803] [Abstract] Cited for: MUTAGENESIS.
[8]	"Plastic adaptation toward mutations in proteins: structural comparison of thymidylate synthases." Perry K.M., Fauman E.B., Finer-Moore J.S., Montfort W.R., Maley G.F., Maley F., Stroud R.M. Proteins 8:315-333(1990) [PubMed: 2128651] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[9]	"Water-mediated substrate/product discrimination: the product complex of thymidylate synthase at 1.83 A." Fauman E.B., Rutenber E.E., Maley G.F., Maley F., Stroud R.M. Biochemistry 33:1502-1511(1994) [PubMed: 8312270] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS).
[10]	"An essential role for water in an enzyme reaction mechanism: the crystal structure of the thymidylate synthase mutant E58Q." Sage C.R., Rutenber E.E., Stout T.J., Stroud R.M. Biochemistry 35:16270-16281(1996) [PubMed: 8973201] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT GLN-58.
[11]	"Crystal structures of a marginally active thymidylate synthase mutant, Arg 126-->Glu." Strop P., Changchien L., Maley F., Montfort W.R. Protein Sci. 6:2504-2511(1997) [PubMed: 9416600] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT GLU-126.
[12]	"Inactivity of N229A thymidylate synthase due to water-mediated effects: isolating a late stage in methyl transfer." Reyes C.L., Sage C.R., Rutenber E.E., Nissen R.M., Finer-Moore J.S., Stroud R.M. J. Mol. Biol. 284:699-712(1998) [PubMed: 9826509] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT ALA-177.
[13]	"Site-directed ligand discovery." Erlanson D.A., Braisted A.C., Raphael D.R., Randal M., Stroud R.M., Gordon E.M., Wells J.A. Proc. Natl. Acad. Sci. U.S.A. 97:9367-9372(2000) [PubMed: 10944209] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

SYECT. A00549.

RefSeq

AP_003390.1.
NP_417304.1.

3D structure databases

PDBMSD

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	3-264	[»]
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	[»]
2G8M	X-ray	1.30	A/B	1-264	[»]
2G8O	X-ray	1.30	A/B	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	[»]
3TMS	X-ray	2.10	A	1-264	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P0A884.

2-D gel databases

ECO2DBASE

G029.3. 6TH EDITION.

Genome annotation databases

GeneID

949035.

GenomeReviews

Gene locus b2827 in contig U00096_GR.
Gene locus JW2795 in contig AP009048_GR.

KEGG

ecj:JW2795.
eco:b2827.

Organism-specific databases

EchoBASE

EB0995.

EcoGene

EG11002. thyA.

CMR

Search...

Phylogenomic databases

HOGENOM

P0A884.

Enzyme and pathway databases

BioCyc

EcoCyc:THYMIDYLATESYN-MON.
MetaCyc:THYMIDYLATESYN-MON.

Family and domain databases

HAMAP

MF_00008.
[Tree]

InterPro

IPR000398. Thymidylat_synth_C.
[Graphical view]

Gene3D

G3DSA:3.30.572.10. Thymidylat_synth_C. 1 hit.

PANTHER

PTHR11549:SF2. Thymidylat_synth_C. 1 hit.

Pfam

PF00303. Thymidylat_synt. 1 hit.
[Graphical view]

PRINTS

PR00108. THYMDSNTHASE.

ProDom

PD001180. Thymidylat_synth. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR03284. thym_sym. 1 hit.

PROSITE

PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

BLOCKS

Search...

Other Resources

BindingDB

P0A884.

LinkHub

P0A884.

ProtoNet

Search...

Entry information

Entry name

TYSY_ECOLI

Accession

Primary (citable) accession number: P0A884
Secondary accession number(s): P00470, Q2MA10

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	September 2, 2008
This is version 37 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)