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NMNAT2
Identifiers
Aliases	NMNAT2, C1orf15, PNAT2, nicotinamide nucleotide adenylyltransferase 2
External IDs	OMIM: 608701; MGI: 2444155; HomoloGene: 75037; GeneCards: NMNAT2; OMA:NMNAT2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q25.3 Start 183,248,237 bp End 183,418,380 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 G3 Start 152,830,744 bp End 152,995,007 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in middle temporal gyrus frontal pole paraflocculus of cerebellum Brodmann area 10 orbitofrontal cortex cerebellar vermis Brodmann area 23 right hemisphere of cerebellum Brodmann area 46 superior frontal gyrus Top expressed in medial dorsal nucleus cerebellar cortex visual cortex superior cervical ganglion dentate gyrus of hippocampal formation granule cell central gray substance of midbrain dorsomedial hypothalamic nucleus lateral geniculate nucleus primary visual cortex cerebellar vermis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding nucleotidyltransferase activity catalytic activity nicotinamide-nucleotide adenylyltransferase activity ATP binding nicotinate-nucleotide adenylyltransferase activity Cellular component cytoplasm Golgi membrane late endosome Golgi apparatus trans-Golgi network synapse membrane axon cytoplasmic vesicle membrane cytoplasmic vesicle cell projection Biological process pyridine nucleotide biosynthetic process NAD metabolic process biosynthesis NAD biosynthetic process 'de novo' NAD biosynthetic process from aspartate nucleotide biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23057 226518 Ensembl ENSG00000157064 ENSMUSG00000042751 UniProt Q9BZQ4 Q8BNJ3 RefSeq (mRNA) NM_170706 NM_015039 NM_175460 RefSeq (protein) NP_055854 NP_733820 NP_780669 Location (UCSC) Chr 1: 183.25 – 183.42 Mb Chr 1: 152.83 – 153 Mb PubMed search
Wikidata
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Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an enzyme that in humans is encoded by the NMNAT2 gene.

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), 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. By contrast, NMNAT2 enhancement opposes the actions of SARM1 which would lead to axon degeneration, but this effect is not due to preventing SARM1 depletion of NAD+. Mice lacking NMNAT2 die before birth, but are completely rescued by SARM1 deletion. Activation of NMNAT2 by Sirtuin 3 (SIRT3) may be a means of inhibiting axon degeneration and dysfunction.

The catechin epigallocatechin gallate (EGCG) found in tea can activate NMNAT2 by more than 100%.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000157064 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000042751 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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 (Apr 2001). "Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus". Genomics. 73 (2): 211–22. doi:10.1006/geno.2001.6500. PMID 11318611.
6. Raffaelli N, Sorci L, Amici A, Emanuelli M, Mazzola F, Magni G (Oct 2002). "Identification of a novel human nicotinamide mononucleotide adenylyltransferase". Biochem Biophys Res Commun. 297 (4): 835–40. doi:10.1016/S0006-291X(02)02285-4. PMID 12359228.
7. ^ "Entrez Gene: NMNAT2 nicotinamide nucleotide adenylyltransferase 2".
8. Cambronne XA, Kraus WL (2020). "Location, Location, Location: Compartmentalization of NAD + Synthesis and Functions in Mammalian Cells". Trends in Biochemical Sciences. 45 (10): 858–873. doi:10.1016/j.tibs.2020.05.010. PMC 7502477. PMID 32595066.
9. ^ Brazill JM, Li C, Zhu Y, Zhai RG (2017). "NMNAT: It's an NAD + Synthase… It's a Chaperone… It's a Neuroprotector". Current Opinion in Genetics & Development. 44: 156–162. doi:10.1016/j.gde.2017.03.014. PMC 5515290. PMID 28445802.
10. Sasaki Y, Nakagawa T, Mao X, DiAntonio A, Milbrandt J (October 2016). "+ depletion". eLife. 5. doi:10.7554/eLife.19749. PMC 5063586. PMID 27735788.
11. Yaku K, Okabe K, Nakagawa T (2018). "NAD metabolism: Implications in aging and longevity". Ageing Research Reviews. 47: 1–17. doi:10.1016/j.arr.2018.05.006. PMID 29883761. S2CID 47002665.
12. Gilley J, Ribchester RR, Coleman MP (October 2017). "S, Confers Lifelong Rescue in a Mouse Model of Severe Axonopathy". Cell Reports. 21 (1): 10–16. doi:10.1016/j.celrep.2017.09.027. PMC 5640801. PMID 28978465.
13. Zhang J, Xiang H, Rong-Rong He R, Liu B (2020). "Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target". Theranostics. 10 (18): 8315–8342. doi:10.7150/thno.45922. PMC 7381741. PMID 32724473.
14. Rajman L, Chwalek K, Sinclair DA (2018). "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence". Cell Metabolism. 27 (3): 529–547. doi:10.1016/j.cmet.2018.02.011. PMC 6342515. PMID 29514064.

Further reading

• Seki N, Ohira M, Nagase T, et al. (1998). "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain". DNA Res. 4 (5): 345–9. doi:10.1093/dnares/4.5.345. PMID 9455484.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Yalowitz JA, Xiao S, Biju MP, et al. (2004). "Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas". Biochem. J. 377 (Pt 2): 317–26. doi:10.1042/BJ20030518. PMC 1223862. PMID 14516279.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Berger F, Lau C, Dahlmann M, Ziegler M (2006). "Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms". J. Biol. Chem. 280 (43): 36334–41. doi:10.1074/jbc.M508660200. PMID 16118205.
• Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
• Sorci L, Cimadamore F, Scotti S, et al. (2007). "Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis". Biochemistry. 46 (16): 4912–22. doi:10.1021/bi6023379. PMID 17402747.

• Genes on human chromosome 1