NUDT3
Description
The NUDT3 (nudix hydrolase 3) is a protein-coding gene located on chromosome 6.
Diphosphoinositol polyphosphate phosphohydrolase 1 is an enzyme that in humans is encoded by the NUDT3 gene. NUDT3 belongs to the MutT, or Nudix, protein family.
NUDT3 hydrolyzes diphosphoinositol polyphosphates, such as PP-InsP5 and [PP]2-InsP4, suggesting a role in signal transduction. It also acts as a negative regulator of the ERK1/2 pathway. NUDT3 catalyzes the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being preferred substrates. NUDT3 also hydrolyzes 5-phosphoribose 1-diphosphate. Additionally, NUDT3 functions as a decapping enzyme, modulating the stability of certain mRNAs involved in cell motility. It hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates, generating m7GMP + ppRNA and m7GDP + pRNA. NUDT3 can also hydrolyze unmethylated capped RNAs. The substrate specificity of NUDT3 is determined by divalent cations such as zinc, magnesium, and manganese. In the presence of magnesium ions, NUDT3 exhibits diphosphoinositol polyphosphate phosphohydrolase activity, while in the presence of manganese ions, it exhibits diadenosine hexaphosphate hydrolase activity. Zinc ions induce endopolyphosphatase activity in NUDT3. NUDT3 plays a crucial role in limiting DNA damage and maintaining cell survival upon oxidative stress through its endopolyphosphatase activity. {ECO:0000250|UniProtKB:Q9JI46, ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413, ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:34788624, ECO:0000269|PubMed:9822604, ECO:0000305|PubMed:26932476}
NUDT3 is also known as DIPP, DIPP-1, DIPP1.
