NMNAT-2: Proteins and Enzymes

NMNAT-1 is expressed in the nuclei of all human tissues, with highest expression in skeletal muscle, heart, kidney, pancreas, and brain. The enzyme transfers adenylate from ATP to nicotinamide ribonucleotide or nicotinate ribonucleotide to generate NAD+ or deamido-NAD+, and is an essential enzyme for the production of nuclear NAD+. Nuclear NAD+ is required by poly(ADP-ribose) polymerase 1 (PARP-1), which poly-ADP-ribosylates chromatin in response to DNA strand breaks. NMNAT-1 is known to interact with PARP-1, resulting in its activation, but this interaction with PARP-1 is prevented when NMNAT-1 is phosphorylated at Ser136. Nuclear NAD+ levels are also important for the regulation of SIR2 histone deacetylases. A naturally occurring Ube4b/NMNAT-1 chimeric protein is directly involved in slowing the degeneration of injured neurons in mice. NMNAT activity is required for the activation of tiazofurin, a drug used to treat leukemia. Two other NMNAT enzymes are present in humans. NMNAT-2 is localized in the Golgi complex and cytoplasm, and NMNAT-3 is a mitochondrial enzyme.