Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1

Details

Name
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
Synonyms
  • 2.7.7.1
  • NaMN adenylyltransferase 1
  • Nicotinamide-nucleotide adenylyltransferase 1
  • Nicotinate-nucleotide adenylyltransferase 1
  • NMN adenylyltransferase 1
  • NMN/NaMN adenylyltransferase 1
  • NMNAT
Gene Name
NMNAT1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016569|Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1
MENSEKTEVVLLACGSFNPITNMHLRLFELAKDYMNGTGRYTVVKGIISPVGDAYKKKGL
IPAYHRVIMAELATKNSKWVEVDTWESLQKEWKETLKVLRHHQEKLEASDCDHQQNSPTL
ERPGRKRKWTETQDSSQKKSLEPKTKAVPKVKLLCGADLLESFAVPNLWKSEDITQIVAN
YGLICVTRAGNDAQKFIYESDVLWKHRSNIHVVNEWIANDISSTKIRRALRRGQSIRYLV
PDLVQEYIEKHNLYSSESEDRNAGVILAPLQRNTAEAKT
Number of residues
279
Molecular Weight
31932.22
Theoretical pI
9.24
GO Classification
Functions
ATP binding / nicotinamide-nucleotide adenylyltransferase activity / nicotinate-nucleotide adenylyltransferase activity
Processes
'de novo' NAD biosynthetic process from aspartate / NAD biosynthetic process / NAD metabolic process / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process
Components
nucleoplasm / nucleus
General Function
Nicotinate-nucleotide adenylyltransferase activity
Specific Function
Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+). Protects against axonal degeneration following mechanical or toxic insults.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0016570|Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1)
ATGGAAAATTCCGAGAAGACTGAAGTGGTTCTCCTTGCTTGTGGTTCATTCAATCCCATC
ACCAACATGCACCTCAGGTTGTTTGAGCTGGCCAAGGACTACATGAATGGAACAGGAAGG
TACACAGTTGTCAAAGGCATCATCTCTCCTGTTGGTGATGCCTACAAGAAGAAAGGACTC
ATTCCTGCCTATCACCGGGTCATCATGGCAGAACTTGCTACCAAGAATTCTAAATGGGTG
GAAGTTGATACATGGGAAAGTCTTCAGAAGGAGTGGAAAGAGACTCTGAAGGTGCTAAGA
CACCATCAAGAGAAATTGGAGGCTAGTGACTGTGATCACCAGCAGAACTCACCTACTCTA
GAAAGGCCTGGAAGGAAGAGGAAGTGGACTGAAACACAAGATTCTAGTCAAAAGAAATCC
CTAGAGCCAAAAACAAAAGCTGTGCCAAAGGTCAAGCTGCTGTGTGGGGCAGATTTATTG
GAGTCCTTTGCTGTTCCCAATTTGTGGAAGAGTGAAGACATCACCCAAATCGTGGCCAAC
TATGGGCTCATATGTGTTACTCGGGCTGGAAATGATGCTCAGAAGTTTATCTATGAATCG
GATGTGCTGTGGAAACACCGGAGCAACATTCACGTGGTGAATGAATGGATCGCTAATGAC
ATCTCATCCACAAAAATCCGGAGAGCCCTCAGAAGGGGCCAGAGCATTCGCTACTTGGTA
CCAGATCTTGTCCAAGAATACATTGAAAAGCATAATTTGTACAGCTCTGAGAGTGAAGAC
AGGAATGCTGGGGTCATCCTGGCCCCTTTGCAGAGAAACACTGCAGAAGCTAAGACATAG
Chromosome Location
1
Locus
1p32-p35
External Identifiers
ResourceLink
UniProtKB IDQ9HAN9
UniProtKB Entry NameNMNA1_HUMAN
GenBank Protein ID11245478
GenBank Gene IDAF314163
GenAtlas IDNMNAT1
HGNC IDHGNC:17877
General References
  1. Schweiger M, Hennig K, Lerner F, Niere M, Hirsch-Kauffmann M, Specht T, Weise C, Oei SL, Ziegler M: Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis. FEBS Lett. 2001 Mar 9;492(1-2):95-100. [Article]
  2. Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G: Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase. J Biol Chem. 2001 Jan 5;276(1):406-12. [Article]
  3. Fernando FS, Conforti L, Tosi S, Smith AD, Coleman MP: Human homologue of a gene mutated in the slow Wallerian degeneration (C57BL/Wld(s)) mouse. Gene. 2002 Feb 6;284(1-2):23-9. [Article]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Zhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H: Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J Biol Chem. 2003 Apr 11;278(15):13503-11. Epub 2003 Feb 6. [Article]
  8. Berger F, Lau C, Dahlmann M, Ziegler M: Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms. J Biol Chem. 2005 Oct 28;280(43):36334-41. Epub 2005 Aug 23. [Article]
  9. Sorci L, Cimadamore F, Scotti S, Petrelli R, Cappellacci L, Franchetti P, Orsomando G, Magni G: 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. 2007 Apr 24;46(16):4912-22. Epub 2007 Apr 3. [Article]
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  11. Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Li Y, Fishman GA, Genead M, Schwartzentruber J, Solanki N, Traboulsi EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson CA, Nageeb M, Poulter JA, Mohamed MD, Jafri H, Rashid Y, Taylor GR, Keser V, Mardon G, Xu H, Inglehearn CF, Fu Q, Toomes C, Chen R: Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nat Genet. 2012 Sep;44(9):1035-9. doi: 10.1038/ng.2356. Epub 2012 Jul 29. [Article]
  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  13. Werner E, Ziegler M, Lerner F, Schweiger M, Heinemann U: Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN. FEBS Lett. 2002 Apr 10;516(1-3):239-44. [Article]
  14. Garavaglia S, D'Angelo I, Emanuelli M, Carnevali F, Pierella F, Magni G, Rizzi M: Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis. J Biol Chem. 2002 Mar 8;277(10):8524-30. Epub 2001 Dec 19. [Article]
  15. Zhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, Zhang H: Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin. J Biol Chem. 2002 Apr 12;277(15):13148-54. Epub 2002 Jan 11. [Article]
  16. Chiang PW, Wang J, Chen Y, Fu Q, Zhong J, Chen Y, Yi X, Wu R, Gan H, Shi Y, Chen Y, Barnett C, Wheaton D, Day M, Sutherland J, Heon E, Weleber RG, Gabriel LA, Cong P, Chuang K, Ye S, Sallum JM, Qi M: Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):972-4. doi: 10.1038/ng.2370. Epub 2012 Jul 29. [Article]
  17. Perrault I, Hanein S, Zanlonghi X, Serre V, Nicouleau M, Defoort-Delhemmes S, Delphin N, Fares-Taie L, Gerber S, Xerri O, Edelson C, Goldenberg A, Duncombe A, Le Meur G, Hamel C, Silva E, Nitschke P, Calvas P, Munnich A, Roche O, Dollfus H, Kaplan J, Rozet JM: Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. Nat Genet. 2012 Sep;44(9):975-7. doi: 10.1038/ng.2357. Epub 2012 Jul 29. [Article]
  18. Falk MJ, Zhang Q, Nakamaru-Ogiso E, Kannabiran C, Fonseca-Kelly Z, Chakarova C, Audo I, Mackay DS, Zeitz C, Borman AD, Staniszewska M, Shukla R, Palavalli L, Mohand-Said S, Waseem NH, Jalali S, Perin JC, Place E, Ostrovsky J, Xiao R, Bhattacharya SS, Consugar M, Webster AR, Sahel JA, Moore AT, Berson EL, Liu Q, Gai X, Pierce EA: NMNAT1 mutations cause Leber congenital amaurosis. Nat Genet. 2012 Sep;44(9):1040-5. doi: 10.1038/ng.2361. Epub 2012 Jul 29. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB03227Nicotinamide MononucleotideexperimentalunknownDetails
DB04099Deamido-Nad+experimentalunknownDetails