S-methyl-5'-thioadenosine phosphorylase (MTAP)

S-methyl-5'-thioadenosine phosphorylase (MTAP) is an enzyme involved in the methionine salvage pathway and polyamine metabolism, catalyzing the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) into adenine and 5-methylthioribose-1-phosphate. In humans, it is encoded by the MTAP gene, located at chromosome 9p21.3. MTAP plays a critical role in recycling adenine and methionine from MTA, a byproduct of polyamine synthesis. MTAP deficiency or deletion is frequently observed in various cancers and is associated with the deletion of neighboring tumor suppressor genes such as p16/CDKN2A, making MTAP an important biomarker and potential synthetic lethality target in oncology. MTAP is classified as a glycosyltransferase (pentosyltransferase family), and it exhibits broad substrate specificity for 6-aminopurine nucleosides. While no approved drugs directly target MTAP, its status as a tumor vulnerability is under investigation for new cancer therapies.

Other names

5'-methylthioadenosine phosphorylaseMTAPaseMTA phosphorylaseMeSAdo phosphorylaseMeSAdo/Ado phosphorylase5'-methylthioadenosine nucleosidasemethylthioadenosine phosphorylasemethylthioadenosine nucleoside phosphorylase5'-deoxy-5'-methylthioadenosine phosphorylase5'-methylthioadenosine:phosphate methylthio-D-ribosyl-transferaseEC 2.4.2.28

Inhibition of MTAP activity can lead to accumulation of MTA, influencing polyamine biosynthesis and tumor cell biology. MTAP-targeted therapeutics could work by exploiting MTAP deficiency in tumors, especially for synthetic lethality with agents targeting metabolic vulnerabilities or exploiting methylthioadenosine accumulation. Modulation of the methionine salvage pathway.