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),[8] and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene.[7]
Loss of NMNAT2 initiates Wallerian degeneration.[9] By contrast, NMNAT2 enhancement opposes the actions of SARM1 which would lead to axon degeneration,[10] but this effect is not due to preventing SARM1 depletion of NAD+.[9] Mice lacking NMNAT2 die before birth,[11] but are completely rescued by SARM1 deletion.[12] Activation of NMNAT2 by Sirtuin 3 (SIRT3) may be a means of inhibiting axon degeneration and dysfunction.[13]
^ abcGRCh38: Ensembl release 89: ENSG00000157064 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000042751 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.
^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.
^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. PMC7502477. PMID 32595066.
^ abBrazill 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. PMC5515290. PMID 28445802.
^Sasaki Y, Nakagawa T, Mao X, DiAntonio A, Milbrandt J (October 2016). "+ depletion". eLife. 5. doi:10.7554/eLife.19749. PMC5063586. PMID 27735788.
^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.
^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. PMC5640801. PMID 28978465.
^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. PMC7381741. PMID 32724473.
^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. PMC6342515. PMID 29514064.
Further readingedit
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. PMC139241. 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. PMC1223862. 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. PMC528928. 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.
May 10, 2024
nmnat2, nicotinamide, mononucleotide, adenylyltransferase, enzyme, that, humans, encoded, gene, identifiersaliases, c1orf15, pnat2, nicotinamide, nucleotide, adenylyltransferase, 2external, idsomim, 608701, 2444155, homologene, 75037, genecards, gene, location. Nicotinamide mononucleotide adenylyltransferase 2 NMNAT2 is an enzyme that in humans is encoded by the NMNAT2 gene 5 6 7 NMNAT2IdentifiersAliasesNMNAT2 C1orf15 PNAT2 nicotinamide nucleotide adenylyltransferase 2External IDsOMIM 608701 MGI 2444155 HomoloGene 75037 GeneCards NMNAT2Gene location Human Chr Chromosome 1 human 1 Band1q25 3Start183 248 237 bp 1 End183 418 380 bp 1 Gene location Mouse Chr Chromosome 1 mouse 2 Band1 1 G3Start152 830 744 bp 2 End152 995 007 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmiddle temporal gyrusfrontal poleBrodmann area 10orbitofrontal cortexcerebellar vermisBrodmann area 23Brodmann area 46superior frontal gyrusmiddle frontal gyruspostcentral gyrusTop expressed inmedial dorsal nucleuscerebellar cortexvisual cortexsuperior cervical gangliondorsomedial hypothalamic nucleuslateral geniculate nucleuscerebellar vermismedial geniculate nucleussuperior frontal gyrussupraoptic nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontransferase activity nucleotide binding nucleotidyltransferase activity catalytic activity nicotinamide nucleotide adenylyltransferase activity ATP binding nicotinate nucleotide adenylyltransferase activityCellular componentcytoplasm Golgi membrane late endosome Golgi apparatus trans Golgi network synapse membrane axon cytoplasmic vesicle membrane cytoplasmic vesicle cell projectionBiological processpyridine nucleotide biosynthetic process NAD metabolic process biosynthesis NAD biosynthetic process de novo NAD biosynthetic process from aspartate nucleotide biosynthetic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez23057226518EnsemblENSG00000157064ENSMUSG00000042751UniProtQ9BZQ4Q8BNJ3RefSeq mRNA NM 170706NM 015039NM 175460RefSeq protein NP 055854NP 733820NP 780669Location UCSC Chr 1 183 25 183 42 MbChr 1 152 83 153 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse 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 8 and is predominantly expressed in the brain Two transcript variants encoding different isoforms have been found for this gene 7 Loss of NMNAT2 initiates Wallerian degeneration 9 By contrast NMNAT2 enhancement opposes the actions of SARM1 which would lead to axon degeneration 10 but this effect is not due to preventing SARM1 depletion of NAD 9 Mice lacking NMNAT2 die before birth 11 but are completely rescued by SARM1 deletion 12 Activation of NMNAT2 by Sirtuin 3 SIRT3 may be a means of inhibiting axon degeneration and dysfunction 13 The catechin epigallocatechin gallate EGCG found in tea can activate NMNAT2 by more than 100 14 References edit a b c GRCh38 Ensembl release 89 ENSG00000157064 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000042751 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 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 a b Entrez Gene NMNAT2 nicotinamide nucleotide adenylyltransferase 2 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 a b 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 amp Development 44 156 162 doi 10 1016 j gde 2017 03 014 PMC 5515290 PMID 28445802 Sasaki Y Nakagawa T Mao X DiAntonio A Milbrandt J October 2016 depletion eLife 5 doi 10 7554 eLife 19749 PMC 5063586 PMID 27735788 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 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 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 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 editSeki 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 Retrieved from https en wikipedia org w index php title NMNAT2 amp oldid 1188036606, wikipedia, wiki, 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