Thymidylate synthase

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Thymidylate synthetase

Ribbon diagram of human thymidylate synthetase in complex with dUMP (orange) and raltitrexed (lime green). From PDB 1HVY.

Available structures: 1hvy, 1hw3, 1hw4, 1hzw, 1i00, 1ju6, 1juj, 1ypv, 2onb

Identifiers

Symbol(s)

TYMS; TS; HsT422; MGC88736; TMS; TSase

External IDs

OMIM: 188350 MGI: 98878 HomoloGene: 834

Gene ontology
Molecular Function:	• thymidylate synthase activity • methyltransferase activity • transferase activity
Biological Process:	• nucleobase, nucleoside, nucleotide and nucleic acid metabolic process • dTMP biosynthetic process • DNA replication • DNA repair • deoxyribonucleoside monophosphate biosynthetic process • nucleotide biosynthetic process • phosphoinositide-mediated signaling

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_001071 (mRNA)
NP_001062 (protein)

NM_021288 (mRNA)
NP_067263 (protein)

Location

Chr 18: 0.65 - 0.66 Mb

Chr 5: 30.39 - 30.4 Mb

Pubmed search

[1]

[2]

Thymidylate synthetase (EC 2.1.1.45)^[1] is the enzyme used to generate thymidine monophosphate (dTMP), which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair. By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product.

As an anti-cancer chemotherapy target, thymidylate synthetase can be inhibited by the fluorinated pyrimidine fluorouracil, or certain folate analogues, including most notably raltitrexed (trade name Tomudex).

1 See also
2 References
3 Further reading
4 External links

[edit] See also

Pyrimidine analogues

[edit] References

^ Entrez Gene: TYMS thymidylate synthetase.

[edit] Further reading

Carreras CW, and Santi DV (1995). "The Catalytic Mechanism and Structure of Thymidylate Synthase". Annual Review of Biochemistry 64 (1): 721–762. PMID 7574499.
Banerjee D, Mayer-Kuckuk P, Capiaux G, et al. (2002). "Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase.". Biochim. Biophys. Acta 1587 (2-3): 164–73. PMID 12084458.
Liu J, Schmitz JC, Lin X, et al. (2002). "Thymidylate synthase as a translational regulator of cellular gene expression.". Biochim. Biophys. Acta 1587 (2-3): 174–82. PMID 12084459.
Chu J, Dolnick BJ (2002). "Natural antisense (rTSalpha) RNA induces site-specific cleavage of thymidylate synthase mRNA.". Biochim. Biophys. Acta 1587 (2-3): 183–93. PMID 12084460.
Peters GJ, Backus HH, Freemantle S, et al. (2002). "Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism.". Biochim. Biophys. Acta 1587 (2-3): 194–205. PMID 12084461.
Costi MP, Tondi D, Rinaldi M, et al. (2002). "Structure-based studies on species-specific inhibition of thymidylate synthase.". Biochim. Biophys. Acta 1587 (2-3): 206–14. PMID 12084462.
Lin D, Li H, Tan W, et al. (2007). "Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development.". Forum of nutrition 60: 140–5. doi:10.1159/0000107090. PMID 17684410.

[edit] External links

MeSH Thymidylate+synthetase

This article on a gene on chromosome 18 is a stub. You can help Wikipedia by expanding it.

v • d • e Transferase: one carbon transferases (EC 2.1)

2.1.1 - Methyltransferases	N-methyltransferase: Histamine N-methyltransferase - Phenylethanolamine N-methyltransferase - Tryptamine N-methyltransferase - Phosphatidylethanolamine N-methyltransferase O-methyltransferase: 5-hydroxyindole-O-methyltransferase/Acetylserotonin O-methyltransferase - Catechol-O-methyl transferase homocysteine methyltransferase: Betaine-homocysteine methyltransferase - Homocysteine methyltransferase - 5-Methyltetrahydrofolate-homocysteine methyltransferase Other: Phosphatidyl ethanolamine methyltransferase - DNMT3B - Histone methyltransferase - Thymidylate synthase - DNA methyltransferase

2.1.2 - Hydroxy methyl-, Formyl- and Related Transferases	Serine hydroxymethyltransferase - Phosphoribosylglycinamide formyltransferase - Inosine monophosphate synthase - Glutamate formimidoyltransferase - Aminomethyltransferase

2.1.3 - Carboxy- and Carbamoyl transferases	Ornithine transcarbamylase

2.1.4 - Amidino transferases	Arginine:glycine amidinotransferase

v • d • e

Metabolism: amino acid metabolism - nucleotide enzymes

Purine metabolism

Anabolism	synthesis: Amidophosphoribosyltransferase - Inosine monophosphate synthase GMP (IMP dehydrogenase, GMP synthase, GMP reductase) AMP (Adenylosuccinate synthase, Adenylosuccinate lyase, AMP deaminase)

Nucleotide salvage	Hypoxanthine-guanine phosphoribosyltransferase - Adenine phosphoribosyltransferase

Catabolism	Adenosine deaminase - Purine nucleoside phosphorylase - Guanine deaminase - Xanthine oxidase - Urate oxidase

Pyrimidine metabolism

Anabolism	CAD (Carbamoyl phosphate synthase II, Aspartate carbamoyltransferase, Dihydroorotase) Dihydroorotate dehydrogenase - Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase CTP synthase

Catabolism	Dihydropyrimidine dehydrogenase - Dihydropyrimidinase/DPYS - Beta-ureidopropionase/UPB1