Identification of a novel human nicotinamide mononucleotide adenylyltransferase
Abstract
The enzyme nicotinamide mononucleotide adenylyltransferase is an ubiquitous enzyme catalyzing an essential step in NAD (NADP) biosynthetic pathway. In human cells, the nuclear enzyme, which we will now call NMNAT-1, has been the only known enzyme of this type for over 10 years. Here we describe the cloning and expression of a human cDNA encoding a novel 34.4kDa protein, that shares significant homology with the 31.9kDa NMNAT-1. We propose to call this enzyme NMNAT-2. Purified recombinant NMNAT-2 is endowed with NMN and nicotinic acid mononucleotide adenylyltransferase activities, but differs from NMNAT-1 with regard to chromosomal and cellular localization, tissue-specificity of expression, and molecular properties, supporting the idea that the two enzymes might play distinct physiological roles in NAD homeostasis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Three mammalian homologs NMNAT1-3 have been identified, with NMNAT2 being the most labile of the three isoforms with a half-life of approximately 4 h.
“Three mammalian homologs, NMNAT1 -3, have been identified (24)(25)(26), with NMNAT2 (nicotinamide mononucleotide adenylyltransferase 2) being the most labile of the three isoforms with a half-life of ,4 h (27).”
The differential subcellular distribution of NMNAT1, NMNAT2 and NMNAT3 is consistent with previous observations that found NMNAT1 in the nucleus, NMNAT2 in the Golgi complex and neurites and NMNAT3 in the mitochondria.
“This differential subcellular distribution is consistent with previous observations that found NMNAT1 in the nucleus, NMNAT2 in the Golgi complex and neurites and NMNAT3 in the mitochondria (25,26,55,56).”
Cites
Emanuelli, M., Carnevali, F., Saccucci, F., Pierella, F., Amici, A., Raffaelli, N., & Magni, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008700200 · Cited by 189 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Ying, W. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1672 · Cited by 1,494 · see citing works
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways
Houtkooper, R. H., Cantó, C., Wanders, R. J., & Auwerx, J. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0026 · Cited by 899 · see citing works
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681 · see citing works
NAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627 · see citing works
Berger, F., Lau, C., Dahlmann, M., & Ziegler, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508660200 · Cited by 508 · see citing works
Endogenous Nmnat2 Is an Essential Survival Factor for Maintenance of Healthy Axons
Gilley, J., & Coleman, M. P. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000300 · Cited by 472 · see citing works
The new life of a centenarian: signalling functions of NAD(P)
Berger, F. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.01.007 · Cited by 489 · see citing works
Sasaki, Y., Araki, T., & Milbrandt, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2320-06.2006 · Cited by 269 · see citing works
NAD metabolism: Implications in aging and longevity
Yaku, K., Okabe, K., & Nakagawa, T. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.05.006 · Cited by 269 · see citing works
The role of NAD biosynthesis in plant development and stress responses
Hashida, S.-N., Takahashi, H., & Uchimiya, H. (2009) · Annals of Botany · doi:10.1093/aob/mcp019 · Cited by 195 · see citing works
NAD<sup>+</sup>metabolism and oxidative stress: the golden nucleotide on a crown of thorns
Massudi, H., Grant, R., Guillemin, G. J., & Braidy, N. (2012) · Redox Report · doi:10.1179/1351000212y.0000000001 · Cited by 158 · see citing works
Yahata, N., Yuasa, S., & Araki, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4304-08.2009 · Cited by 154 · see citing works
“Since NMNAT2 is constitutively expressed highly in neurons (Raffaelli et al., 2002), we decided to generate mice that overexpress mammalian NMNAT orthologs other than NMNAT2 (i.e., NMNAT1 and NMNAT3, either of which are unexpressed in neurons) (Emanuelli et al., 2001; Zhang et al., 2003).”
BackgroundZhang, X., Kurnasov, O. V., Karthikeyan, S., Grishin, N. V., Osterman, A. L., & Zhang, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300073200 · Cited by 136 · see citing works
Cambronne, X. A., & Kraus, W. L. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.05.010 · Cited by 137 · see citing works
Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis
Wang, G., & Pichersky, E. (2007) · The Plant Journal · doi:10.1111/j.1365-313x.2006.03013.x · Cited by 116 · see citing works
Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · see citing works
Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity
Yan, T., Feng, Y., Zheng, J., Ge, X., Zhang, Y., Wu, D., Zhao, J., & Zhai, Q. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2009.09.007 · Cited by 92 · see citing works
Mayer, P. R., Huang, N., Dewey, C. M., Dries, D. R., Zhang, H., & Yu, G. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.178913 · Cited by 82 · see citing works
- Authors
- Raffaelli, N., Sorci, L., Amici, A., Emanuelli, M., Mazzola, F., & Magni, G.
- Corresponding author
- Magni, Giulio
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 297
- Issue
- 4
- Pages
- 835-840
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2022450215
- Cited by
- 127
- References
- 1
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 9 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 6 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 7 · 2012: 6
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- nicotinamide mononucleotide adenylyltransferase, NAD biosynthesis, cDNA cloning, recombinant enzyme expression, enzyme homology, chromosomal localization, tissue-specific gene expression, NAD+ homeostasis
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Nucleus, Cloning, Molecular, DNA, Humans, Kinetics, Molecular Sequence Data, NAD, NADP, Nicotinamide-Nucleotide Adenylyltransferase, Recombinant Proteins, Saccharomyces cerevisiae, Polymerase Chain Reaction, Sequence Alignment, Sequence Homology, Amino Acid, DNA Primers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
