Thymidylate synthase
Details
- Name
- Thymidylate synthase
- Synonyms
- 2.1.1.45
- TS
- Gene Name
- TYMS
- Organism
- Humans
- 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
- Functionscofactor binding / drug binding / folic acid binding / mRNA binding / nucleotide binding / thymidylate synthase activityProcessesaging / cartilage development / cell growth / cell proliferation / circadian rhythm / deoxyribonucleoside monophosphate biosynthetic process / developmental growth / DNA biosynthetic process / dTMP biosynthetic process / dTTP biosynthetic process / dUMP metabolic process / G1/S transition of mitotic cell cycle / immortalization of host cell by virus / intestinal epithelial cell maturation / mitotic cell cycle / nucleobase-containing compound metabolic process / nucleobase-containing small molecule metabolic process / organ regeneration / pyrimidine nucleobase metabolic process / pyrimidine nucleoside biosynthetic process / regulation of transcription involved in G1/S transition of mitotic cell cycle / response to cytokine / response to drug / response to ethanol / response to folic acid / response to glucocorticoid / response to organophosphorus / response to progesterone / response to toxic substance / response to vitamin A / small molecule metabolic process / tetrahydrofolate interconversion / uracil metabolic processComponentscytoplasm / cytosol / mitochondrial inner membrane / mitochondrial matrix / mitochondrion / nucleolus / nucleoplasm / nucleus
- General Function
- Thymidylate synthase activity
- Specific Function
- Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
- Pfam Domain Function
- Thymidylat_synt (PF00303)
- 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 GenAtlas ID TYMS HGNC ID HGNC:12441 - 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]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00293 Raltitrexed approved, investigational yes inhibitor Details DB00322 Floxuridine approved yes Details DB00544 Fluorouracil approved yes other/unknown Details DB00642 Pemetrexed approved, investigational yes inhibitor Details DB01101 Capecitabine approved, investigational yes inhibitor Details DB00441 Gemcitabine approved unknown inhibitor Details DB03800 Deoxyuridine monophosphate experimental unknown Details DB04530 S,S-(2-Hydroxyethyl)Thiocysteine experimental unknown Details DB01643 Thymidine monophosphate experimental unknown product of Details DB00432 Trifluridine approved, investigational yes inhibitor Details DB05308 ANX-510 investigational unknown Details DB05116 Thymectacin investigational unknown Details DB05457 OSI-7904L investigational unknown Details DB03541 10-Propargyl-5,8-Dideazafolic Acid experimental unknown Details DB07577 2,4-Diamino-5-phenyl-6-ethylpyrimidine experimental unknown Details DB08478 N-[2-Chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide experimental unknown Details DB08479 N-(3,5-dimethoxyphenyl)imidodicarbonimidic diamide experimental unknown Details DB08734 6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE experimental unknown Details DB00544 Fluorouracil approved unknown substrate Details DB00563 Methotrexate approved unknown substrate Details DB06813 Pralatrexate approved, investigational unknown substrateinhibitor Details DB09327 Tegafur-uracil approved, investigational yes antagonist Details DB09256 Tegafur approved, investigational yes inhibitor Details DB00563 Methotrexate approved yes inhibitor Details