NMNAT2
Function
Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor (By similarity). Axon survival factor required for the maintenance of healthy axons: acts by delaying Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons (By similarity). Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:16118205, PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency (PubMed:16118205, PubMed:17402747). Cannot use triazofurin monophosphate (TrMP) as substrate (PubMed:16118205, PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:16118205, PubMed:17402747). For the pyrophosphorolytic activity prefers NAD(+), NADH and NaAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively (PubMed:16118205, PubMed:17402747). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:16118205, PubMed:17402747). Also acts as an activator of ADP-ribosylation by supporting the catalytic activity of PARP16 and promoting mono-ADP-ribosylation of ribosomes by PARP16 (PubMed:34314702).
Pathway
Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1.
Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+) from nicotinate D-ribonucleotide: step 1/1.
Post-translational modifications
Degraded in response to injured neurite (By similarity). Degradation is caused by polyubiquitination by MYCBP2 after recognition by FBXO45 (PubMed:29643511, PubMed:29997255).
Palmitoylated; palmitoylation is required for membrane association.
Sequence Similarities
Belongs to the eukaryotic NMN adenylyltransferase family.
Tissue Specificity
Highly expressed in brain, in particular in cerebrum, cerebellum, occipital lobe, frontal lobe, temporal lobe and putamen. Also found in the heart, skeletal muscle, pancreas and islets of Langerhans.
Cellular localization
- Golgi apparatus membrane
- Lipid-anchor
- Cytoplasmic vesicle membrane
- Lipid-anchor
- Cytoplasm
- Cell projection
- Axon
- Delivered to axons with Golgi-derived cytoplasmic vesicles.
Alternative names
C1orf15, KIAA0479, NMNAT2, Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2, NMN/NaMN adenylyltransferase 2, Nicotinamide mononucleotide adenylyltransferase 2, Nicotinate-nucleotide adenylyltransferase 2, NMN adenylyltransferase 2, NaMN adenylyltransferase 2