thiopurine S-methyltransferase; thiopurine methyltransferase (TPMT)

Function: - catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine Structure: - monomer - belongs to the methyltransferase superfamily, TPMT family Compartment: cytoplasm Polymorphism: - individual variation in the toxicity & 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 ~90% of Caucasians have high TPMT activity, 10% have intermediate activity & 1 in 300 individuals has low activity - TPMT activity varies among ethnic groups - TPMT*3A is the only mutant allele found in South West Asians; this is also the most common mutant allele in Caucasians, but is not found in Chinese - all mutant alleles identified in the Chinese population were TPMT*3C; this allele is found at a low frequency in 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 & South West Asian populations - TPMT*2 appears to be a more recent allele, which has only been detected in Caucasians to date - ethnic differences may be important in the clinical use of thiopurine drugs Pathology: - defects in TPMT are the cause of: a) thiopurine S-methyltransferase deficiency b) disruption of normal metabolic inactivation of thiopurine drugs

Related

thiopurine methyltransferase (TPMT) gene mutation thiopurine methyltransferase in erythrocytes

General

phosphoprotein S-methyltransferase

Properties

SIZE: entity length = 245 aa MW = 28 kD COMPARTMENT: cytoplasm MOTIF: Ser phosphorylation site {S14} binding site SITE: 33-33 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 69-69 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 90-90 FOR-BINDING-OF: S-adenosylmethionine binding site SITE: 152-152 FOR-BINDING-OF: S-adenosylmethionine

Database Correlations

OMIM correlations MORBIDMAP 187680 UniProt P51580 Pfam PF05724 Entrez Gene 7172 Kegg hsa:7172 ENZYME 2.1.1.67

References

UniProt :accession P51580