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Showing Protein Thiopurine S-methyltransferase (HMDBP00428)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 12 metabolites
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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  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 ]
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  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 ]
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  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 ]
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  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 ]
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