Thymidylate synthase

NameThymidylate synthase
Synonyms
  • 2.1.1.45
  • TS
Gene NameTYMS
OrganismHuman
Amino acid sequence
>lcl|BSEQ0036991|Thymidylate synthase
MPVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFG
MQARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDS
LGFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMC
AWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHI
TGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEG
YNPHPTIKMEMAV
Number of residues313
Molecular Weight35715.65
Theoretical pI7.0
GO Classification
Functions
  • drug binding
  • nucleotide binding
  • cofactor binding
  • mRNA binding
  • thymidylate synthase activity
  • folic acid binding
Processes
  • pyrimidine nucleobase metabolic process
  • tetrahydrofolate interconversion
  • pyrimidine nucleoside biosynthetic process
  • dTMP biosynthetic process
  • dTTP biosynthetic process
  • cartilage development
  • nucleobase-containing small molecule metabolic process
  • deoxyribonucleoside monophosphate biosynthetic process
  • circadian rhythm
  • developmental growth
  • response to glucocorticoid
  • dUMP metabolic process
  • response to toxic substance
  • immortalization of host cell by virus
  • mitotic cell cycle
  • response to drug
  • intestinal epithelial cell maturation
  • DNA biosynthetic process
  • organ regeneration
  • nucleobase-containing compound metabolic process
  • regulation of transcription involved in G1/S transition of mitotic cell cycle
  • G1/S transition of mitotic cell cycle
  • cell growth
  • response to folic acid
  • response to ethanol
  • cell proliferation
  • response to organophosphorus
  • aging
  • small molecule metabolic process
  • response to progesterone
  • response to vitamin A
  • response to cytokine
  • uracil metabolic process
Components
  • nucleolus
  • nucleoplasm
  • cytoplasm
  • mitochondrion
  • nucleus
  • mitochondrial inner membrane
  • mitochondrial matrix
  • cytosol
General FunctionThymidylate synthase activity
Specific FunctionContributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID37479
UniProtKB IDP04818
UniProtKB Entry NameTYSY_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0010247|Thymidylate synthase (TYMS)
ATGCCTGTGGCCGGCTCGGAGCTGCCGCGCCGGCCCTTGCCCCCCGCCGCACAGGAGCGG
GACGCCGAGCCGCGTCCGCCGCACGGGGAGCTGCAGTACCTGGGGCAGATCCAACACATC
CTCCGCTGCGGCGTCAGGAAGGACGACCGCACGGGCACCGGCACCCTGTCGGTATTCGGC
ATGCAGGCGCGCTACAGCCTGAGAGATGAATTCCCTCTGCTGACAACCAAACGTGTGTTC
TGGAAGGGTGTTTTGGAGGAGTTGCTGTGGTTTATCAAGGGATCCACAAATGCTAAAGAG
CTGTCTTCCAAGGGAGTGAAAATCTGGGATGCCAATGGATCCCGAGACTTTTTGGACAGC
CTGGGATTCTCCACCAGAGAAGAAGGGGACTTGGGCCCAGTTTATGGCTTCCAGTGGAGG
CATTTTGGGGCAGAATACAGAGATATGGAATCAGATTATTCAGGACAGGGAGTTGACCAA
CTGCAAAGAGTGATTGACACCATCAAAACCAACCCTGACGACAGAAGAATCATCATGTGC
GCTTGGAATCCAAGAGATCTTCCTCTGATGGCGCTGCCTCCATGCCATGCCCTCTGCCAG
TTCTATGTGGTGAACAGTGAGCTGTCCTGCCAGCTGTACCAGAGATCGGGAGACATGGGC
CTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC
ACGGGCCTGAAGCCAGGTGACTTTATACACACTTTGGGAGATGCACATATTTACCTGAAT
CACATCGAGCCACTGAAAATTCAGCTTCAGCGAGAACCCAGACCTTTCCCAAAGCTCAGG
ATTCTTCGAAAAGTTGAGAAAATTGATGACTTCAAAGCTGAAGACTTTCAGATTGAAGGG
TACAATCCGCATCCAACTATTAAAATGGAAATGGCTGTTTAG
GenBank Gene IDX02308
GeneCard IDNot Available
GenAtlas IDTYMS
HGNC IDHGNC:12441
Chromosome Location18
Locus18p11.32
References
  1. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Res. 1985 Mar 25;13(6):2035-43. 2987839
  2. Kaneda S, Nalbantoglu J, Takeishi K, Shimizu K, Gotoh O, Seno T, Ayusawa D: Structural and functional analysis of the human thymidylate synthase gene. J Biol Chem. 1990 Nov 25;265(33):20277-84. 2243092
  3. Hisatomi H, Tanemura H, Iizuka T, Katsumata K, Nagao K, Sumida H, Udagawa H, Hikiji K: Differential alternative splicing expressions of thymidylate synthase isoforms. Cancer Lett. 2003 Apr 25;193(2):127-31. 12706868
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  6. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Human thymidylate synthase gene: isolation of phage clones which cover a functionally active gene and structural analysis of the region upstream from the translation initiation codon. J Biochem. 1989 Oct;106(4):575-83. 2532645
  7. Shimizu K, Ayusawa D, Takeishi K, Seno T: Purification and NH2-terminal amino acid sequence of human thymidylate synthase in an overproducing transformant of mouse FM3A cells. J Biochem. 1985 Mar;97(3):845-50. 3839505
  8. Davisson VJ, Sirawaraporn W, Santi DV: Expression of human thymidylate synthase in Escherichia coli. J Biol Chem. 1989 Jun 5;264(16):9145-8. 2656695
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  11. Anderson DD, Quintero CM, Stover PJ: Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi: 10.1073/pnas.1103623108. Epub 2011 Aug 26. 21876188
  12. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  13. Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM: Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry. 1995 Dec 19;34(50):16279-87. 8845352
  14. Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L: Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001 Feb 20;40(7):1897-902. 11329255
  15. Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L: Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors. J Biol Chem. 2001 Apr 27;276(17):14170-7. Epub 2001 Jan 24. 11278511