Cytosolic 5′-nucleotidase III (NT5C3): gene sequence variation and functional genomics

Abstract

The His283 and T276/His283 constructs showed decreased levels of enzyme activity and protein. Substrate kinetic analysis showed no significant differences in Km values between wild type and His283 when cytidine monophosphate, AraCMP, and GemMP were used as substrates. An association study between single nucleotide polymorphisms (SNPs) and NT5C3 expression in the 240 cell lines from which DNA was extracted to resequence NT5C3 identified four SNPs that were significantly associated with NT5C3 expression. Electrophoretic mobility shift assays showed that two of those SNPs, I4(-114) and I6(9), altered DNA-protein binding patterns. These findings suggest that genetic variation in NT5C3 might affect protein function and potentially influence drug response.