5',3'-nucleotidase, cytosolic (NT5C)

5',3'-nucleotidase, cytosolic (NT5C) is an intracellular enzyme of the haloacid dehalogenase superfamily that catalyzes the dephosphorylation of purine and pyrimidine nucleoside monophosphates, playing a key role in maintaining nucleotide pool homeostasis by clearing excess intracellular nucleotides[1][2]. NT5C preferentially hydrolyzes inosine monophosphate (IMP), guanosine monophosphate (GMP), xanthosine monophosphate (XMP), and their deoxyribose counterparts. It forms a homotetramer structurally and is regulated through allosteric activation by nucleotide effectors such as ATP and dATP[1]. In oncology, NT5C is clinically significant as it can inactivate thiopurine drugs (6-MP, 6-TG) used in leukemia treatment, and activating NT5C2 mutations confer resistance to these agents in relapsed cases of acute lymphoblastic leukemia[1]. Loss-of-function mutations are linked to hereditary spastic paraplegia. The gene encoding this enzyme is NT5C; its structure and mechanism have been well characterized, including key motifs involved in catalysis and allosteric regulation[1][2].

Other names

5'(3')-deoxyribonucleotidase, cytosolic typecdNdeoxy-5'-nucleotidase 1dNT-1DNT1UMPH2PN-IP5N2PN-IIcytosolic 5',3'-pyrimidine nucleotidaseUridine 5'-monophosphate phosphohydrolase 2Uridine 5-prime monophosphate hydrolase 2epididymis luminal protein 74

Dephosphorylation and inactivation of thiopurine analog monophosphates (6-MP and 6-TG active metabolites) leading to decreased cytotoxic efficacy in leukemia[1]