NMNAT1

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NMNAT1
Protein NMNAT1 PDB 1gzu.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NMNAT1, LCA9, NMNAT, PNAT1, nicotinamide nucleotide adenylyltransferase 1
External IDs MGI: 1913704 HomoloGene: 39074 GeneCards: NMNAT1
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001297778
NM_001297779
NM_022787

NM_133435

RefSeq (protein)

NP_001284707
NP_001284708
NP_073624

NP_597679

Location (UCSC) Chr 1: 9.94 – 9.99 Mb Chr 4: 149.47 – 149.49 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Nicotinamide mononucleotide adenylyltransferase 1 is an enzyme that in humans is encoded by the NMNAT1 gene.[3][4][5] It is a member of the nicotinamide-nucleotide adenylyltransferases.

Function[edit]

The coenzyme NAD and its derivatives are involved in hundreds of metabolic redox reactions and are utilized in protein ADP-ribosylation, histone deacetylation, and in some Ca2+ signaling pathways. NMNAT (EC 2.7.7.1) is a central enzyme in NAD biosynthesis, catalyzing the condensation of nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) with the AMP moiety of ATP to form NAD or NaAD.[5]

NMNAT1 is the most widely expressed of three orthologous genes with nicotinamide-nucleotide adenylyltransferase (NMNAT) activity. Genetically engineered mice lacking NMNAT1 die during early embryogenesis, indicating a critical role of this gene in organismal viability.[citation needed] In contrast, mice lacking NMNAT2, which is expressed predominantly in neural tissues, complete development but die shortly after birth. However, NMNAT1 is dispensable for cell viability, as homozygous deletion of this gene occurs in glioblastoma tumors and cell lines. NMNAT enzymatic activity is probably essential at the cellular level, as complete ablation of NMNAT activity in model organisms leads to cellular inviability.[6]

Clinical relevance[edit]

Mutations in this gene have been shown associated to retinal degeneration pathologies, like Leber's congenital amaurosis.[7]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Schweiger M, Hennig K, Lerner F, Niere M, Hirsch-Kauffmann M, Specht T, Weise C, Oei SL, Ziegler M (Mar 2001). "Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis". FEBS Lett. 492 (1–2): 95–100. PMID 11248244. doi:10.1016/S0014-5793(01)02180-9. 
  4. ^ Emanuelli M, Carnevali F, Saccucci F, Pierella F, Amici A, Raffaelli N, Magni G (Feb 2001). "Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase". J Biol Chem. 276 (1): 406–12. PMID 11027696. doi:10.1074/jbc.M008700200. 
  5. ^ a b "Entrez Gene: NMNAT1 nicotinamide nucleotide adenylyltransferase 1". 
  6. ^ Muller FL, Colla S, Aquilanti E, et al. (August 2012). "Passenger deletions generate therapeutic vulnerabilities in cancer". Nature. 488 (7411): 337–42. PMC 3712624Freely accessible. PMID 22895339. doi:10.1038/nature11331. 
  7. ^ 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 (September 2012). Finding of Rare Disease Genes (FORGE) Canada Consortium. "Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration". Nat. Genet. 44 (9): 1035–9. PMC 3657614Freely accessible. PMID 22842230. doi:10.1038/ng.2356. 

Further reading[edit]