TYMP (gene) explained

TYMP is a gene that encodes for the enzyme thymidine phosphorylase.^{[1] [2]} The TYMP gene is also known as ECGF1 (endothelial cell growth factor 1, platelet-derived) and MNGIE due to its role in MNGIE syndrome. ^[3]

Structure

The TYMP gene is located on chromosome 22 in humans and contains 10 exons spanning more than 4.3 kb.

Function

TYMP encodes for the enzyme thymidine phosphorylase. TYMP and thymidine phosphorylase are associated with angiogenesis, growth of endothelial cells, and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).

Thymidine phosphorylase is angiogenic growth factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. Thymidine phosphorylase has a highly restricted target cell specificity acting only on endothelial cells, hence its alternative name of ECGF1. Because it limits glial cell proliferation, thymidine phosphorylase is also known as gliostatin. Thymidine phosphorylase activity in leukocytes from mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients was less than 5 percent of controls, indicating that loss-of-function mutations in TYMP cause MNGIE.^[4]

Further reading

• Yang Q, Yoshimura G, Mori I . Thymidine phosphorylase and breast carcinoma. . Anticancer Res. . 22 . 4 . 2355–60 . 2002 . 12174926 . etal.
• Asai K, Nakanishi K, Isobe I . Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor. . J. Biol. Chem. . 267 . 28 . 20311–6 . 1992 . 10.1016/S0021-9258(19)88703-3 . 1400349 . etal. free .
• Furukawa T, Yoshimura A, Sumizawa T . Angiogenic factor. . Nature . 356 . 6371 . 668 . 1992 . 1570012 . 10.1038/356668a0 . 1992Natur.356..668F . etal. free .
• Stenman G, Sahlin P, Dumanski JP . Regional localization of the human platelet-derived endothelial cell growth factor (ECGF1) gene to chromosome 22q13. . Cytogenet. Cell Genet. . 59 . 1 . 22–3 . 1992 . 1733667 . 10.1159/000133191 . etal.
• Hagiwara K, Stenman G, Honda H . Organization and chromosomal localization of the human platelet-derived endothelial cell growth factor gene . Mol. Cell. Biol. . 11 . 4 . 2125–32 . 1991 . 2005900 . 10.1128/MCB.11.4.2125. 359900 . etal.
• Ishikawa F, Miyazono K, Hellman U . Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor . Nature . 338 . 6216 . 557–62 . 1989 . 2467210 . 10.1038/338557a0 . 1989Natur.338..557I . 4337444 . etal.
• Bardosi A, Creutzfeldt W, DiMauro S . Myo-, neuro-, gastrointestinal encephalopathy (MNGIE syndrome) due to partial deficiency of cytochrome-c-oxidase. A new mitochondrial multisystem disorder . Acta Neuropathol. . 74 . 3 . 248–58 . 1987 . 2823522 . 10.1007/BF00688189 . 20379299 . etal.
• Miyazono K, Okabe T, Urabe A . Purification and properties of an endothelial cell growth factor from human platelets . J. Biol. Chem. . 262 . 9 . 4098–103 . 1987 . 10.1016/S0021-9258(18)61316-X . 3549724 . etal. free .
• Usuki K, Gonez LJ, Wernstedt C . Structural properties of 3.0 kb and 3.2 kb transcripts encoding platelet-derived endothelial cell growth factor/thymidine phosphorylase in A431 cells . Biochim. Biophys. Acta . 1222 . 3 . 411–4 . 1994 . 8038210 . 10.1016/0167-4889(94)90049-3 . etal.
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Hirano M, Silvestri G, Blake DM . Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical, biochemical, and genetic features of an autosomal recessive mitochondrial disorder . Neurology . 44 . 4 . 721–7 . 1994 . 8164833 . 10.1212/wnl.44.4.721. 31980361 . etal.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Stevenson DP, Milligan SR, Collins WP . Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase, substrate, and products in a three-dimensional model of angiogenesis . Am. J. Pathol. . 152 . 6 . 1641–6 . 1998 . 9626068 . 1858429 .
• Nishino I, Spinazzola A, Hirano M . Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder . Science . 283 . 5402 . 689–92 . 1999 . 9924029 . 10.1126/science.283.5402.689 . 1999Sci...283..689N .
• Asgari MM, Haggerty JG, McNiff JM . Expression and localization of thymidine phosphorylase/platelet-derived endothelial cell growth factor in skin and cutaneous tumors . J. Cutan. Pathol. . 26 . 6 . 287–94 . 1999 . 10472757 . 10.1111/j.1600-0560.1999.tb01846.x . 32158847 . etal.
• Loftus BJ, Kim UJ, Sneddon VP . Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q . Genomics . 60 . 3 . 295–308 . 1999 . 10493829 . 10.1006/geno.1999.5927 . etal.
• Sivridis E, Giatromanolaki A, Koukourakis MI . Thymidine phosphorylase expression in normal and hyperplastic endometrium . J. Clin. Pathol. . 53 . 9 . 704–8 . 2000 . 11041061 . 10.1136/jcp.53.9.704 . 1731246 . etal.
• Komatsu T, Yamazaki H, Shimada N . Involvement of microsomal cytochrome P450 and cytosolic thymidine phosphorylase in 5-fluorouracil formation from tegafur in human liver . Clin. Cancer Res. . 7 . 3 . 675–81 . 2001 . 11297264 . etal.
• Kojima H, Shijubo N, Abe S . Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma . Cancer . 94 . 4 . 1083–93 . 2002 . 11920479 . 10.1002/cncr.10352 . 35877612 .

External links

• GeneReviews/NIH/NCBI/UW entry on Mitochondrial Neurogastrointestinal Encephalopathy Disease (MNGIE)

Notes and References

1. 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 . 184 . 3 . 1311–6 . Jun 1992 . 1590793 . 10.1016/S0006-291X(05)80025-7 .
2. Spinazzola A, Marti R, Nishino I, Andreu AL, Naini A, Tadesse S, Pela I, Zammarchi E, Donati MA, Oliver JA, Hirano M . Altered thymidine metabolism due to defects of thymidine phosphorylase . J Biol Chem . 277 . 6 . 4128–33 . Feb 2002 . 11733540 . 10.1074/jbc.M111028200 . free .
3. Web site: Gene symbol report | HUGO Gene Nomenclature Committee.
4. Web site: Entrez Gene: ECGF1 endothelial cell growth factor 1 (platelet-derived).