ID:TPMT_HUMAN DESCRIPTION: RecName: Full=Thiopurine S-methyltransferase; EC=2.1.1.67; AltName: Full=Thiopurine methyltransferase; FUNCTION: Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + a thiopurine = S- adenosyl-L-homocysteine + a thiopurine S-methylether. ENZYME REGULATION: Inhibited by S-adenosyl-L-homocysteine (SAH). BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.6 mM for S-adenosyl-L-methionine; KM=0.35 mM for 6-mercaptopurine; Vmax=0.6 nmol/sec/mg enzyme toward 6-mercaptopurine (at 37 degrees Celsius); SUBUNIT: Monomer. SUBCELLULAR LOCATION: Cytoplasm. POLYMORPHISM: Individual variation in the toxicity and therapeutic efficacy of thiopurine drugs is associated with a common genetic polymorphism that controls levels of TPMT activity. Genetic polymorphism in the TPMT gene is such that about 90% of Caucasians have high TPMT activity, 10% have intermediate activity and 1 in 300 individuals has low activity. TPMT activity varies among ethnic groups. POLYMORPHISM: TPMT*3A is the only mutant allele found in the South West Asians. This is also the most common mutant allele in the Caucasians but is not found in the Chinese. All mutant alleles identified in the Chinese population were TPMT*3C. This allele is found at a low frequency in the Caucasians. This suggests that TPMT*3C is the oldest mutation, with TPMT*3B being acquired later to form the TPMT*3A allele in the Caucasian and South West Asian populations. TPMT*2 appears to be a more recent allele, which has only been detected in Caucasians to date. These ethnic differences may be important in the clinical use of thiopurine drugs. DISEASE: Defects in TPMT are the cause of thiopurine S- methyltransferase deficiency (TPMT deficiency) [MIM:610460]. TPMT is an enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosupressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus. MISCELLANEOUS: TPMT deficiency inherited by TPMT*2 and TPMT*3A alleles, are the most prevalent mutant TPMT in humans. TPMT deficiency is associated with lower cellular levels of TPMT protein, and the proteins encoded by TPMT*2 and TPMT*3A mutant alleles are degraded more rapidly by an ATP-dependent proteasome- mediated pathway. SIMILARITY: Belongs to the methyltransferase superfamily. TPMT family. SEQUENCE CAUTION: Sequence=AAB71631.1; Type=Erroneous initiation; Sequence=AAB71632.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P51580
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
