Thymidylate synthase
Details
- Name
- Thymidylate synthase
- Kind
- protein
- Synonyms
- 2.1.1.45
- TS
- TSase
- Gene Name
- TYMS
- UniProtKB Entry
- P04818Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0036991|Thymidylate synthase MPVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFG MQARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDS LGFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMC AWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHI TGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEG YNPHPTIKMEMAV
- Number of residues
- 313
- Molecular Weight
- 35715.65
- Theoretical pI
- 7.0
- GO Classification
- FunctionsmRNA regulatory element binding translation repressor activity / protein homodimerization activity / sequence-specific mRNA bindingProcessesliver regeneration / methylation / negative regulation of translation / response to xenobiotic stimulus
- General Function
- Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway
- Specific Function
- folic acid binding
- Pfam Domain Function
- Thymidylat_synt (PF00303)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Nucleus
- Gene sequence
>lcl|BSEQ0010247|Thymidylate synthase (TYMS) ATGCCTGTGGCCGGCTCGGAGCTGCCGCGCCGGCCCTTGCCCCCCGCCGCACAGGAGCGG GACGCCGAGCCGCGTCCGCCGCACGGGGAGCTGCAGTACCTGGGGCAGATCCAACACATC CTCCGCTGCGGCGTCAGGAAGGACGACCGCACGGGCACCGGCACCCTGTCGGTATTCGGC ATGCAGGCGCGCTACAGCCTGAGAGATGAATTCCCTCTGCTGACAACCAAACGTGTGTTC TGGAAGGGTGTTTTGGAGGAGTTGCTGTGGTTTATCAAGGGATCCACAAATGCTAAAGAG CTGTCTTCCAAGGGAGTGAAAATCTGGGATGCCAATGGATCCCGAGACTTTTTGGACAGC CTGGGATTCTCCACCAGAGAAGAAGGGGACTTGGGCCCAGTTTATGGCTTCCAGTGGAGG CATTTTGGGGCAGAATACAGAGATATGGAATCAGATTATTCAGGACAGGGAGTTGACCAA CTGCAAAGAGTGATTGACACCATCAAAACCAACCCTGACGACAGAAGAATCATCATGTGC GCTTGGAATCCAAGAGATCTTCCTCTGATGGCGCTGCCTCCATGCCATGCCCTCTGCCAG TTCTATGTGGTGAACAGTGAGCTGTCCTGCCAGCTGTACCAGAGATCGGGAGACATGGGC CTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC ACGGGCCTGAAGCCAGGTGACTTTATACACACTTTGGGAGATGCACATATTTACCTGAAT CACATCGAGCCACTGAAAATTCAGCTTCAGCGAGAACCCAGACCTTTCCCAAAGCTCAGG ATTCTTCGAAAAGTTGAGAAAATTGATGACTTCAAAGCTGAAGACTTTCAGATTGAAGGG TACAATCCGCATCCAACTATTAAAATGGAAATGGCTGTTTAG
- Chromosome Location
- 18
- Locus
- 18p11.32
- External Identifiers
Resource Link UniProtKB ID P04818 UniProtKB Entry Name TYSY_HUMAN GenBank Protein ID 37479 GenBank Gene ID X02308 GeneCard ID TYMS GenAtlas ID TYMS HGNC ID HGNC:12441 PDB ID(s) 1HVY, 1HW3, 1HW4, 1HZW, 1I00, 1JU6, 1JUJ, 1YPV, 2ONB, 2RD8, 2RDA, 3EAW, 3EBU, 3ED7, 3EDW, 3EF9, 3EGY, 3EHI, 3EJL, 3GG5, 3GH0, 3GH2, 3H9K, 3HB8, 3N5E, 3N5G, 3OB7, 4E28, 4FGT, 4G2O, 4G6W, 4GD7, 4GYH, 4H1I, 4JEF, 4KPW, 4O1U, 4O1X, 4UP1, 5HS3, 5WRN, 5X4W, 5X4X, 5X4Y, 5X5A, 5X5D, 5X5Q, 5X66, 5X67, 5X69, 6OJU, 6OJV, 6PF3, 6PF4, 6PF5, 6PF6, 6QXG, 6QXH, 6QYQ, 6R2E, 6ZXO KEGG ID hsa:7298 IUPHAR/Guide To Pharmacology ID 2642 NCBI Gene ID 7298 - General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, DeCaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES: DNA sequence and analysis of human chromosome 18. Nature. 2005 Sep 22;437(7058):551-5. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- 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. [Article]
- 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. [Article]
- Davisson VJ, Sirawaraporn W, Santi DV: Expression of human thymidylate synthase in Escherichia coli. J Biol Chem. 1989 Jun 5;264(16):9145-8. [Article]
- Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
- Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Raltitrexed approved, investigational yes target inhibitor Details Floxuridine approved yes target Details Fluorouracil approved yes target other/unknown Details Pemetrexed approved, investigational yes target inhibitor Details Capecitabine approved, investigational yes target inhibitor Details Gemcitabine approved unknown target inhibitor Details Deoxyuridine monophosphate experimental unknown target Details S,S-(2-Hydroxyethyl)Thiocysteine experimental unknown target Details Thymidine monophosphate experimental unknown target product of Details Trifluridine approved, investigational yes target inhibitor Details ANX-510 investigational unknown target Details Thymectacin investigational unknown target Details OSI-7904L investigational unknown target Details 10-Propargyl-5,8-Dideazafolic Acid experimental unknown target Details 2,4-Diamino-5-phenyl-6-ethylpyrimidine experimental unknown target Details N-[2-Chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide experimental unknown target Details N-(3,5-dimethoxyphenyl)imidodicarbonimidic diamide experimental unknown target Details 6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE experimental unknown target Details Fluorouracil approved unknown enzyme substrate Details Methotrexate approved unknown enzyme substrate Details Pralatrexate approved, investigational unknown target substrateinhibitor Details Tegafur-uracil approved, investigational yes target antagonist Details Tegafur approved, investigational yes target inhibitor Details Methotrexate approved yes target inhibitor Details Fosifloxuridine nafalbenamide investigational yes target inhibitor Details