Thymidine phosphorylase

Details

Name
Thymidine phosphorylase
Synonyms
  • 2.4.2.4
  • ECGF1
  • Gliostatin
  • PD-ECGF
  • Platelet-derived endothelial cell growth factor
  • TdRPase
  • TP
Gene Name
TYMP
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004303|Thymidine phosphorylase
MAALMTPGTGAPPAPGDFSGEGSQGLPDPSPEPKQLPELIRMKRDGGRLSEADIRGFVAA
VVNGSAQGAQIGAMLMAIRLRGMDLEETSVLTQALAQSGQQLEWPEAWRQQLVDKHSTGG
VGDKVSLVLAPALAACGCKVPMISGRGLGHTGGTLDKLESIPGFNVIQSPEQMQVLLDQA
GCCIVGQSEQLVPADGILYAARDVTATVDSLPLITASILSKKLVEGLSALVVDVKFGGAA
VFPNQEQARELAKTLVGVGASLGLRVAAALTAMDKPLGRCVGHALEVEEALLCMDGAGPP
DLRDLVTTLGGALLWLSGHAGTQAQGAARVAAALDDGSALGRFERMLAAQGVDPGLARAL
CSGSPAERRQLLPRAREQEELLAPADGTVELVRALPLALVLHELGAGRSRAGEPLRLGVG
AELLVDVGQRLRRGTPWLRVHRDGPALSGPQSRALQEALVLSDRAPFAAPSPFAELVLPP
QQ
Number of residues
482
Molecular Weight
49954.965
Theoretical pI
5.19
GO Classification
Functions
phosphorylase activity / platelet-derived growth factor receptor binding / pyrimidine-nucleoside phosphorylase activity / thymidine phosphorylase activity / transferase activity, transferring pentosyl groups
Processes
angiogenesis / cell differentiation / chemotaxis / DNA replication / mitochondrial genome maintenance / nucleobase-containing small molecule metabolic process / pyrimidine nucleobase metabolic process / pyrimidine nucleoside catabolic process / pyrimidine nucleoside salvage / pyrimidine nucleotide metabolic process / small molecule metabolic process
Components
cytosol
General Function
Transferase activity, transferring pentosyl groups
Specific Function
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0020602|Thymidine phosphorylase (TYMP)
ATGGCAGCCTTGATGACCCCGGGAACCGGGGCCCCACCCGCGCCTGGTGACTTCTCCGGG
GAAGGGAGCCAGGGACTTCCCGACCCTTCGCCAGAGCCCAAGCAGCTCCCGGAGCTGATC
CGCATGAAGCGAGACGGAGGCCGCCTGAGCGAAGCGGACATCAGGGGCTTCGTGGCCGCT
GTGGTGAATGGGAGCGCGCAGGGCGCACAGATCGGGGCCATGCTGATGGCCATCCGACTT
CGGGGCATGGATCTGGAGGAGACCTCGGTGCTGACCCAGGCCCTGGCTCAGTCGGGACAG
CAGCTGGAGTGGCCAGAGGCCTGGCGCCAGCAGCTTGTGGACAAGCATTCCACAGGGGGT
GTGGGTGACAAGGTCAGCCTGGTCCTCGCACCTGCCCTGGCGGCATGTGGCTGCAAGGTG
CCAATGATCAGCGGACGTGGTCTGGGGCACACAGGAGGCACCTTGGATAAGCTGGAGTCT
ATTCCTGGATTCAATGTCATCCAGAGCCCAGAGCAGATGCAAGTGCTGCTGGACCAGGCG
GGCTGCTGTATCGTGGGTCAGAGTGAGCAGCTGGTTCCTGCGGACGGAATCCTATATGCA
GCCAGAGATGTGACAGCCACCGTGGACAGCCTGCCACTCATCACAGCCTCCATTCTCAGT
AAGAAACTCGTGGAGGGGCTGTCCGCTCTGGTGGTGGACGTTAAGTTCGGAGGGGCCGCC
GTCTTCCCCAACCAGGAGCAGGCCCGGGAGCTGGCAAAGACGCTGGTTGGCGTGGGAGCC
AGCCTAGGGCTTCGGGTCGCGGCAGCGCTGACCGCCATGGACAAGCCCCTGGGTCGCTGC
GTGGGCCACGCCCTGGAGGTGGAGGAGGCGCTGCTCTGCATGGACGGCGCAGGCCCGCCA
GACTTAAGGGACCTGGTCACCACGCTCGGGGGCGCCCTGCTCTGGCTCAGCGGACACGCG
GGGACTCAGGCCCAGGGCGCTGCCCGGGTGGCCGCGGCGCTGGACGACGGCTCGGCCCTT
GGCCGCTTCGAGCGGATGCTGGCGGCGCAGGGCGTGGATCCCGGTCTGGCCCGAGCCCTG
TGCTCGGGAAGTCCCGCAGAACGCCGGCAGCTGCTGCCTCGCGCCCGGGAGCAGGAGGAG
CTGCTGGCGCCCGCAGATGGCACCGTGGAGCTGGTCCGGGCGCTGCCGCTGGCGCTGGTG
CTGCACGAGCTCGGGGCCGGGCGCAGCCGCGCTGGGGAGCCGCTCCGCCTGGGGGTGGGC
GCAGAGCTGCTGGTCGACGTGGGTCAGAGGCTGCGCCGTGGGACCCCCTGGCTCCGCGTG
CACCGGGACGGCCCCGCGCTCAGCGGCCCGCAGAGCCGCGCCCTGCAGGAGGCGCTCGTA
CTCTCCGACCGCGCGCCATTCGCCGCCCCCTCGCCCTTCGCAGAGCTCGTTCTGCCGCCG
CAGCAATAA
Chromosome Location
22
Locus
22q13|22q13.33
External Identifiers
ResourceLink
UniProtKB IDP19971
UniProtKB Entry NameTYPH_HUMAN
GenBank Protein ID189701
GenBank Gene IDM63193
GenAtlas IDECGF1
HGNC IDHGNC:3148
General References
  1. Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, Usuki K, Takaku F, Risau W, Heldin CH: Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature. 1989 Apr 13;338(6216):557-62. [PubMed:2467210]
  2. Finnis C, Goodey A, Courtney M, Sleep D: Expression of recombinant platelet-derived endothelial cell growth factor in the yeast Saccharomyces cerevisiae. Yeast. 1992 Jan;8(1):57-60. [PubMed:1580101]
  3. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. [PubMed:10591208]
  4. 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. [PubMed:15489334]
  5. Furukawa T, Yoshimura A, Sumizawa T, Haraguchi M, Akiyama S, Fukui K, Ishizawa M, Yamada Y: Angiogenic factor. Nature. 1992 Apr 23;356(6371):668. [PubMed:1570012]
  6. Asai K, Nakanishi K, Isobe I, Eksioglu YZ, Hirano A, Hama K, Miyamoto T, Kato T: Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor. J Biol Chem. 1992 Oct 5;267(28):20311-6. [PubMed:1400349]
  7. Usuki K, Saras J, Waltenberger J, Miyazono K, Pierce G, Thomason A, Heldin CH: Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. Biochem Biophys Res Commun. 1992 May 15;184(3):1311-6. [PubMed:1590793]
  8. 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. [PubMed:21269460]
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  10. Norman RA, Barry ST, Bate M, Breed J, Colls JG, Ernill RJ, Luke RW, Minshull CA, McAlister MS, McCall EJ, McMiken HH, Paterson DS, Timms D, Tucker JA, Pauptit RA: Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor. Structure. 2004 Jan;12(1):75-84. [PubMed:14725767]
  11. El Omari K, Bronckaers A, Liekens S, Perez-Perez MJ, Balzarini J, Stammers DK: Structural basis for non-competitive product inhibition in human thymidine phosphorylase: implications for drug design. Biochem J. 2006 Oct 15;399(2):199-204. [PubMed:16803458]
  12. Mitsiki E, Papageorgiou AC, Iyer S, Thiyagarajan N, Prior SH, Sleep D, Finnis C, Acharya KR: Structures of native human thymidine phosphorylase and in complex with 5-iodouracil. Biochem Biophys Res Commun. 2009 Sep 4;386(4):666-70. doi: 10.1016/j.bbrc.2009.06.104. Epub 2009 Jun 23. [PubMed:19555658]
  13. Nishino I, Spinazzola A, Hirano M: Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999 Jan 29;283(5402):689-92. [PubMed:9924029]
  14. Gamez J, Ferreiro C, Accarino ML, Guarner L, Tadesse S, Marti RA, Andreu AL, Raguer N, Cervera C, Hirano M: Phenotypic variability in a Spanish family with MNGIE. Neurology. 2002 Aug 13;59(3):455-7. [PubMed:12177387]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01101Capecitabineapproved, investigationalunknownsubstrateDetails
DB00322FloxuridineapprovedunknownsubstrateDetails
DB00544FluorouracilapprovedunknownsubstrateDetails
DB00432Trifluridineapproved, investigationalunknownsubstrateDetails
DB00369CidofovirapprovedunknowninhibitorDetails
DB06433TezacitabineinvestigationalunknowninducerDetails
DB09343Tipiracilapproved, investigationalyesinhibitorDetails