NNMT

Nicotinamide N-methyltransferase (NNMT) is an enzyme that in humans is encoded by the NNMT gene.[5] NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide.[6]

NNMT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3ROD, 2IIP
Identifiers
Aliases	NNMT, Nnmt, nicotinamide N-methyltransferase
External IDs	OMIM: 600008 MGI: 1099443 HomoloGene: 4496 GeneCards: NNMT
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q23.2 Start 114,257,787 bp[1] End 114,313,285 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 A5.3|9 26.45 cM Start 48,591,877 bp[2] End 48,605,153 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • methyltransferase activity • transferase activity • nicotinamide N-methyltransferase activity • pyridine N-methyltransferase activity Cellular component • cytoplasm • cytosol Biological process • methylation • animal organ regeneration • response to organonitrogen compound • response to drug • NAD biosynthesis via nicotinamide riboside salvage pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4837	18113
Ensembl	ENSG00000166741	ENSMUSG00000032271
UniProt	P40261	O55239
RefSeq (mRNA)	NM_006169	NM_001311062 NM_010924
RefSeq (protein)	NP_006160 NP_001358974 NP_001358975 NP_001358976	NP_001297991 NP_035054
Location (UCSC)	Chr 11: 114.26 – 114.31 Mb	Chr 9: 48.59 – 48.61 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

NNMT is highly expressed in the human liver.[6] N-methylation is one method by which drug and other xenobiotic compounds are metabolized by the liver.[6] NNMT expression in adipose tissue is associated with obesity and insulin resistance.[6] Human embryonic stem cells expression of NNMT is believed to help maintain the cells in a naive state.[6]

NNMT expression is significantly upregulated in many cancers, including pancreatic cancer where levels of NNMT enzyme correlate with increased risk of death.[7] The cause of these correlations has not been established, but may be related to the fact that NNMT enzyme is an inhibitor of DNA repair.[7] NNMT has been suggested to be a biomarker of cancer.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000166741 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000032271 - 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. Aksoy S, Brandriff BF, Ward A, Little PF, Weinshilboum RM (Mar 1996). "Human nicotinamide N-methyltransferase gene: molecular cloning, structural characterization and chromosomal localization". Genomics. 29 (3): 555–61. doi:10.1006/geno.1995.9966. PMID 8575745.
6. Pissios P (2017). "Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme". Trends in Endocrinology & Metabolism. 28 (5): 340–353. doi:10.1016/j.tem.2017.02.004. PMC 5446048. PMID 28291578.
7. Lu XM, Long H (2018). "Nicotinamide N-methyltransferase as a Potential Marker for Cancer". Neoplasma. 65 (5): 656–663. doi:10.4149/neo_2018_171024N680. PMID 29940773.

Further reading

• Williams AC, Cartwright LS, Ramsden DB (2005). "Parkinson's disease: the first common neurological disease due to auto-intoxication?". QJM : Monthly Journal of the Association of Physicians. 98 (3): 215–26. doi:10.1093/qjmed/hci027. PMID 15728403.
• Sano A, Endo N, Takitani S (1992). "Fluorometric assay of rat tissue N-methyltransferases with nicotinamide and four isomeric methylnicotinamides". Chem. Pharm. Bull. 40 (1): 153–6. doi:10.1248/cpb.40.153. PMID 1533573.
• Aksoy S, Szumlanski CL, Weinshilboum RM (1994). "Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization". J. Biol. Chem. 269 (20): 14835–40. PMID 8182091.
• Scheller T, Orgacka H, Szumlanski CL, Weinshilboum RM (1996). "Mouse liver nicotinamide N-methyltransferase pharmacogenetics: biochemical properties and variation in activity among inbred strains". Pharmacogenetics. 6 (1): 43–53. doi:10.1097/00008571-199602000-00003. PMID 8845860.
• Smith ML, Burnett D, Bennett P, et al. (1998). "A direct correlation between nicotinamide N-methyltransferase activity and protein levels in human liver cytosol". Biochim. Biophys. Acta. 1442 (2–3): 238–44. doi:10.1016/s0167-4781(98)00177-8. PMID 9804963.
• Yan L, Otterness DM, Weinshilboum RM (1999). "Human nicotinamide N-methyltransferase pharmacogenetics: gene sequence analysis and promoter characterization". Pharmacogenetics. 9 (3): 307–16. doi:10.1097/00008571-199906000-00005. PMID 10471062.
• Hubbard MJ, McHugh NJ (2001). "Human ERp29: isolation, primary structural characterisation and two-dimensional gel mapping". Electrophoresis. 21 (17): 3785–96. doi:10.1002/1522-2683(200011)21:17<3785::AID-ELPS3785>3.0.CO;2-2. PMID 11271497.
• Parsons RB, Smith ML, Williams AC, et al. (2002). "Expression of nicotinamide N-methyltransferase (E.C. 2.1.1.1) in the Parkinsonian brain". J. Neuropathol. Exp. Neurol. 61 (2): 111–24. doi:10.1093/jnen/61.2.111. PMID 11853016.
• Kassem HSh, Sangar V, Cowan R, et al. (2002). "A potential role of heat shock proteins and nicotinamide N-methyl transferase in predicting response to radiation in bladder cancer". Int. J. Cancer. 101 (5): 454–60. doi:10.1002/ijc.10631. PMID 12216074.
• 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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Xu J, Capezzone M, Xu X, Hershman JM (2005). "Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells". Mol. Endocrinol. 19 (2): 527–39. doi:10.1210/me.2004-0215. PMID 15486044.
• 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.
• Souto JC, Blanco-Vaca F, Soria JM, et al. (2005). "A Genomewide Exploration Suggests a New Candidate Gene at Chromosome 11q23 as the Major Determinant of Plasma Homocysteine Levels: Results from the GAIT Project". Am. J. Hum. Genet. 76 (6): 925–33. doi:10.1086/430409. PMC 1196452. PMID 15849667.
• Roessler M, Rollinger W, Palme S, et al. (2005). "Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer". Clin. Cancer Res. 11 (18): 6550–7. doi:10.1158/1078-0432.CCR-05-0983. PMID 16166432.
• Xu J, Hershman JM (2006). "Histone deacetylase inhibitor depsipeptide represses nicotinamide N-methyltransferase and hepatocyte nuclear factor-1beta gene expression in human papillary thyroid cancer cells". Thyroid. 16 (2): 151–60. doi:10.1089/thy.2006.16.151. PMID 16676400.