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Identification
HMDB Protein ID HMDBP00428
Secondary Accession Numbers
  • 5665
Name Thiopurine S-methyltransferase
Synonyms
  1. Thiopurine methyltransferase
Gene Name TPMT
Protein Type Unknown
Biological Properties
General Function Involved in thiopurine S-methyltransferase activity
Specific Function Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Pathways
  • Azathioprine Action Pathway
  • Drug metabolism - other enzymes
  • Mercaptopurine Action Pathway
  • Mercaptopurine Metabolism Pathway
  • Thioguanine Action Pathway
Reactions
S-Adenosylmethionine + a thiopurine → S-Adenosylhomocysteine + a thiopurine S-methylether details
Mercaptopurine + S-Adenosylmethionine → 6-Methylmercaptopurine + S-Adenosylhomocysteine details
6-Thioinosine-5'-monophosphate + S-Adenosylmethionine → 6-Methylthiopurine 5'-monophosphate ribonucleotide + S-Adenosylhomocysteine details
6-Thioguanosine monophosphate + S-Adenosylmethionine → 6-Methylthioguanosine monophosphate + S-Adenosylhomocysteine details
GO Classification
Biological Process
small molecule metabolic process
xenobiotic metabolic process
nucleobase-containing compound metabolic process
Cellular Component
cytosol
Component
cell part
intracellular part
cytoplasm
Function
catalytic activity
transferase activity
s-methyltransferase activity
thiopurine s-methyltransferase activity
transferase activity, transferring one-carbon groups
methyltransferase activity
Molecular Function
thiopurine S-methyltransferase activity
Process
metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 6
Locus 6p22.3
SNPs TPMT
Gene Sequence
>738 bp
ATGGATGGTACAAGAACTTCACTTGACATTGAAGAGTACTCGGATACTGAGGTACAGAAA
AACCAAGTACTAACTCTGGAAGAATGGCAAGACAAGTGGGTGAACGGCAAGACTGCTTTT
CATCAGGAACAAGGACATCAGCTATTAAAGAAGCATTTAGATACTTTCCTTAAAGGCAAG
AGTGGACTGAGGGTATTTTTTCCTCTTTGCGGAAAAGCGGTTGAGATGAAATGGTTTGCA
GACCGGGGACACAGTGTAGTTGGTGTGGAAATCAGTGAACTTGGGATACAAGAATTTTTT
ACAGAGCAGAATCTTTCTTACTCAGAAGAACCAATCACCGAAATTCCTGGAACCAAAGTA
TTTAAGAGTTCTTCGGGGAACATTTCATTGTACTGTTGCAGTATTTTTGATCTTCCCAGG
ACAAATATTGGCAAATTTGACATGATTTGGGATAGAGGAGCATTAGTTGCCATTAATCCA
GGTGATCGCAAATGCTATGCAGATACAATGTTTTCCCTCCTGGGAAAGAAGTTTCAGTAT
CTCCTGTGTGTTCTTTCTTATGATCCAACTAAACATCCAGGTCCACCATTTTATGTTCCA
CATGCTGAAATTGAAAGGTTGTTTGGTAAAATATGCAATATACGTTGTCTTGAGAAGGTT
GATGCTTTTGAAGAACGACATAAAAGTTGGGGAATTGACTGTCTTTTTGAAAAGTTATAT
CTACTTACAGAAAAGTAA
Protein Properties
Number of Residues 245
Molecular Weight 28180.09
Theoretical pI 6.23
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Thiopurine S-methyltransferase
MDGTRTSLDIEEYSDTEVQKNQVLTLEEWQDKWVNGKTAFHQEQGHQLLKKHLDTFLKGK
SGLRVFFPLCGKAVEMKWFADRGHSVVGVEISELGIQEFFTEQNLSYSEEPITEIPGTKV
FKSSSGNISLYCCSIFDLPRTNIGKFDMIWDRGALVAINPGDRKCYADTMFSLLGKKFQY
LLCVLSYDPTKHPGPPFYVPHAEIERLFGKICNIRCLEKVDAFEERHKSWGIDCLFEKLY
LLTEK
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P51580
UniProtKB/Swiss-Prot Entry Name TPMT_HUMAN
PDB IDs
GenBank Gene ID S62904
GeneCard ID TPMT
GenAtlas ID TPMT
HGNC ID HGNC:12014
References
General References
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  2. 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 ]
  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  5. 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. [PubMed:19690332 ]
  6. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  7. Han G, Ye M, Zhou H, Jiang X, Feng S, Jiang X, Tian R, Wan D, Zou H, Gu J: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics. 2008 Apr;8(7):1346-61. doi: 10.1002/pmic.200700884. [PubMed:18318008 ]
  8. Honchel R, Aksoy IA, Szumlanski C, Wood TC, Otterness DM, Wieben ED, Weinshilboum RM: Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA. Mol Pharmacol. 1993 Jun;43(6):878-87. [PubMed:8316220 ]
  9. Lee D, Szumlanski C, Houtman J, Honchel R, Rojas K, Overhauser J, Wieben ED, Weinshilboum RM: Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1. Drug Metab Dispos. 1995 Mar;23(3):398-405. [PubMed:7628307 ]
  10. Szumlanski C, Otterness D, Her C, Lee D, Brandriff B, Kelsell D, Spurr N, Lennard L, Wieben E, Weinshilboum R: Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. DNA Cell Biol. 1996 Jan;15(1):17-30. [PubMed:8561894 ]
  11. Krynetski EY, Fessing MY, Yates CR, Sun D, Schuetz JD, Evans WE: Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library. Pharm Res. 1997 Dec;14(12):1672-8. [PubMed:9453052 ]
  12. Otterness D, Szumlanski C, Lennard L, Klemetsdal B, Aarbakke J, Park-Hah JO, Iven H, Schmiegelow K, Branum E, O'Brien J, Weinshilboum R: Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clin Pharmacol Ther. 1997 Jul;62(1):60-73. [PubMed:9246020 ]
  13. Spire-Vayron de la Moureyre C, Debuysere H, Sabbagh N, Marez D, Vinner E, Chevalier ED, Lo Guidice JM, Broly F: Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis. Hum Mutat. 1998;12(3):177-85. [PubMed:9711875 ]
  14. Krynetski EY, Schuetz JD, Galpin AJ, Pui CH, Relling MV, Evans WE: A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):949-53. [PubMed:7862671 ]
  15. Tai HL, Krynetski EY, Yates CR, Loennechen T, Fessing MY, Krynetskaia NF, Evans WE: Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. Am J Hum Genet. 1996 Apr;58(4):694-702. [PubMed:8644731 ]
  16. Leipold G, Schutz E, Haas JP, Oellerich M: Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis. Arthritis Rheum. 1997 Oct;40(10):1896-8. [PubMed:9336428 ]
  17. Tai HL, Krynetski EY, Schuetz EG, Yanishevski Y, Evans WE: Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6444-9. [PubMed:9177237 ]
  18. Ameyaw MM, Collie-Duguid ES, Powrie RH, Ofori-Adjei D, McLeod HL: Thiopurine methyltransferase alleles in British and Ghanaian populations. Hum Mol Genet. 1999 Feb;8(2):367-70. [PubMed:9931345 ]
  19. Hon YY, Fessing MY, Pui CH, Relling MV, Krynetski EY, Evans WE: Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Genet. 1999 Feb;8(2):371-6. [PubMed:9931346 ]
  20. Collie-Duguid ES, Pritchard SC, Powrie RH, Sludden J, Collier DA, Li T, McLeod HL: The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations. Pharmacogenetics. 1999 Feb;9(1):37-42. [PubMed:10208641 ]
  21. Hiratsuka M, Inoue T, Omori F, Agatsuma Y, Mizugaki M: Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population. Mutat Res. 2000 Mar 14;448(1):91-5. [PubMed:10751626 ]
  22. Kurzawski M, Dziewanowski K, Ciechanowski K, Drozdzik M: Severe azathioprine-induced myelotoxicity in a kidney transplant patient with thiopurine S-methyltransferase-deficient genotype (TPMT*3A/*3C). Transpl Int. 2005 May;18(5):623-5. [PubMed:15819814 ]
  23. Lu HF, Shih MC, Chang YS, Chang JY, Ko YC, Chang SJ, Chang JG: Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese. J Clin Pharm Ther. 2006 Feb;31(1):93-8. [PubMed:16476125 ]
  24. Rossino R, Vincis C, Alves S, Prata MJ, Macis MD, Nucaro AL, Schirru E, Congia M: Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia. J Clin Pharm Ther. 2006 Jun;31(3):283-7. [PubMed:16789994 ]