NMNAT2

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an enzyme that in humans is encoded by the NMNAT2 gene.{{cite journal | vauthors = Sood R, Bonner TI, Makalowska I, Stephan DA, Robbins CM, Connors TD, Morgenbesser SD, Su K, Faruque MU, Pinkett H, Graham C, Baxevanis AD, Klinger KW, Landes GM, Trent JM, Carpten JD | title = Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus | journal = Genomics | volume = 73 | issue = 2 | pages = 211–22 |date=Apr 2001 | pmid = 11318611 | doi = 10.1006/geno.2001.6500 | url = https://zenodo.org/record/1229806 }}{{cite journal | vauthors = Raffaelli N, Sorci L, Amici A, Emanuelli M, Mazzola F, Magni G | title = Identification of a novel human nicotinamide mononucleotide adenylyltransferase | journal = Biochem Biophys Res Commun | volume = 297 | issue = 4 | pages = 835–40 |date=Oct 2002 | pmid = 12359228 | doi =10.1016/S0006-291X(02)02285-4 }}{{cite web | title = Entrez Gene: NMNAT2 nicotinamide nucleotide adenylyltransferase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23057}}

This gene product belongs to the nicotinamide-nucleotide adenylyltransferase (NMNAT) enzyme family, members of which catalyze an essential step in the nicotinamide adenine dinucleotide (NAD+ (NADP)) biosynthetic pathway. NMNAT2 is cytoplasmic (associated with the Golgi apparatus),{{cite journal | vauthors=Cambronne XA, Kraus WL | title=Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells | journal= Trends in Biochemical Sciences | volume=45 | issue=10 | pages=858–873 | year=2020 | url=https://www.jbc.org/content/294/52/19831.long | doi = 10.1016/j.tibs.2020.05.010 | pmc=7502477 | pmid=32595066}} and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene.

Loss of NMNAT2 initiates Wallerian degeneration.{{cite journal | vauthors = Brazill JM, Li C, Zhu Y, Zhai RG | title = NMNAT: It's an NAD + Synthase… It's a Chaperone… It's a Neuroprotector | journal = Current Opinion in Genetics & Development | volume = 44 | pages = 156–162 |date=2017 | doi = 10.1016/j.gde.2017.03.014 | pmc =5515290 | pmid = 28445802}} By contrast, NMNAT2 enhancement opposes the actions of SARM1 which would lead to axon degeneration,{{cite journal | vauthors = Sasaki Y, Nakagawa T, Mao X, DiAntonio A, Milbrandt J | title = + depletion | journal = eLife | volume = 5 | date = October 2016 | pmid = 27735788 | pmc = 5063586 | doi = 10.7554/eLife.19749 | doi-access = free }} but this effect is not due to preventing SARM1 depletion of NAD+. Mice lacking NMNAT2 die before birth,{{cite journal | vauthors = Yaku K, Okabe K, Nakagawa T | title = NAD metabolism: Implications in aging and longevity | journal = Ageing Research Reviews | volume = 47 | pages = 1–17 |date=2018 | doi = 10.1016/j.arr.2018.05.006 | pmid = 29883761| s2cid = 47002665 }} but are completely rescued by SARM1 deletion.{{cite journal | vauthors = Gilley J, Ribchester RR, Coleman MP | title = S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy | journal = Cell Reports | volume = 21 | issue = 1 | pages = 10–16 | date = October 2017 | pmid = 28978465 | pmc = 5640801 | doi = 10.1016/j.celrep.2017.09.027 }} Activation of NMNAT2 by Sirtuin 3 (SIRT3) may be a means of inhibiting axon degeneration and dysfunction.{{cite journal | vauthors=Zhang J, Xiang H, Rong-Rong He R, Liu B | title=Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target | journal=Theranostics | volume=10 | issue=18 | pages=8315–8342| year=2020 | doi = 10.7150/thno.45922 | pmc=7381741 | pmid=32724473}}

The catechin epigallocatechin gallate (EGCG) found in tea can activate NMNAT2 by more than 100%.{{cite journal | vauthors = Rajman L, Chwalek K, Sinclair DA | title = Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence | journal = Cell Metabolism | volume = 27 | issue=3 | pages = 529–547 |date=2018 | doi = 10.1016/j.cmet.2018.02.011 | pmc =6342515 | pmid = 29514064}}