NMNAT2
Description
The NMNAT2 (nicotinamide nucleotide adenylyltransferase 2) is a protein-coding gene located on chromosome 1.
NMNAT2 is an enzyme encoded by the NMNAT2 gene in humans. It belongs to the nicotinamide-nucleotide adenylyltransferase (NMNAT) enzyme family, which catalyzes a crucial step in the nicotinamide adenine dinucleotide (NAD+ (NADP)) biosynthesis pathway. NMNAT2 is located in the cytoplasm, specifically associated with the Golgi apparatus, and is primarily expressed in the brain. Two transcript variants encoding different isoforms have been identified for this gene. Loss of NMNAT2 triggers Wallerian degeneration, while its enhancement counteracts the effects of SARM1, preventing axon degeneration. However, this effect is not attributed to inhibiting SARM1 depletion of NAD+. Mice lacking NMNAT2 die before birth but can be completely rescued by deleting SARM1. Sirtuin 3 (SIRT3) can activate NMNAT2, potentially inhibiting axon degeneration and dysfunction. The catechin epigallocatechin gallate (EGCG) found in tea can increase NMNAT2 activity by over 100%.
NMNAT2 acts as an axon maintenance factor by delaying Wallerian axon degeneration, an evolutionarily conserved process that leads to the loss of damaged axons. It catalyzes the formation of NAD+ from nicotinamide mononucleotide (NMN) and ATP, and can also utilize nicotinic acid mononucleotide (NaMN) as a substrate, albeit with lower efficiency. NMNAT2 is unable to utilize triazofurin monophosphate (TrMP) as a substrate. It also catalyzes the reverse reaction, the pyrophosphorolytic cleavage of NAD+, preferring NAD+, NADH, and NaAD as substrates. It degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively and does not cleave phosphorylated dinucleotides NADP+, NADPH, and NaADP+. Additionally, NMNAT2 acts as an activator of ADP-ribosylation by supporting the catalytic activity of PARP16 and promoting mono-ADP-ribosylation of ribosomes by PARP16.
NMNAT2 is also known as C1orf15, PNAT2.
