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| Aliases | NMNAT1 , LCA9, NMNAT, PNAT1, nicotinamide nucleotide adenylyltransferase 1, SHILCA | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 608700 MGI: 1913704 HomoloGene: 39074 GeneCards: NMNAT1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is an enzyme that in humans is encoded by the nmnat1 gene. [5] [6] [7] It is a member of the nicotinamide-nucleotide adenylyltransferases (NMNATs) which catalyze nicotinamide adenine dinucleotide (NAD) synthesis. [8]
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. [7]
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. [9] 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. Other tumors such as osteosarcoma, however, increase the expression of NMNAT1 upon exposure to DNA damaging agents and inactivation of the nmnat1 gene renders these cells more sensitive to chemotherapy with cisplatin. [10] This latter effect involves lowered nuclear NAD levels in NMNAT1 knockout cells and impaired DNA damage sensing by the NAD-dependent DNA break responsive enzyme poly (ADP-ribose) polymerase-1 (PARP1). [10] The dependence of osteosarcoma cells on NMNAT1-derived NAD for the PARP1-dependent DNA repair and survival is not restricted to cisplatin-treated cancer cells but has also been reported to occur in actinomycine D-treated tumor cell lines, as well. [11] These data suggest that nuclear NAD synthesis by NMNAT1 may represent a therapeutic target in osteosarcoma and possibly in other tumors, as well. [10] [11]
NMNAT enzymatic activity is probably essential at the cellular level, as complete ablation of NMNAT activity in model organisms leads to cellular inviability. [12]
NMNAT1 enhancement opposes the actions of SARM1 which would lead to axon degeneration, [13] but this effect is not due to preventing SARM1 depletion of NAD+. [8]
Mutations in this gene have been shown associated to the LCA9 form of the retinal degeneration pathology Leber's congenital amaurosis. [14] [8] [15]
Aged mice show a significant reduction of NMNAT1 gene products in the liver (which is the main site of de novo synthesis of NAD+). [16] All NMNAT gene isoform products also decline with age in mice in kidneys, oocytes, and colons. [16]
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide. NAD exists in two forms: an oxidized and reduced form, abbreviated as NAD+ and NADH (H for hydrogen), respectively.
NADPH oxidase 1 is an enzyme that in humans is encoded by the NOX1 gene.
Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
Nicotinamide phosphoribosyltransferase, formerly known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin for its extracellular form (eNAMPT), is an enzyme that in humans is encoded by the NAMPT gene. The intracellular form of this protein (iNAMPT) is the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide (NMN) which is responsible for most of the NAD+ formation in mammals. iNAMPT can also catalyze the synthesis of NMN from phosphoribosyl pyrophosphate (PRPP) when ATP is present. eNAMPT has been reported to be a cytokine (PBEF) that activates TLR4, that promotes B cell maturation, and that inhibits neutrophil apoptosis.
In enzymology, a 2'-phosphotransferase (EC 2.7.1.160) is an enzyme that catalyzes the chemical reaction
In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) (EC 2.7.7.1) are enzymes that catalyzes the chemical reaction
PITSLRE serine/threonine-protein kinase CDC2L1 is an enzyme that in humans is encoded by the CDC2L1 gene.
Hyaluronan synthase 2 is an enzyme that in humans is encoded by the HAS2 gene.
Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 is an enzyme that in humans is encoded by the ATP2A3 gene.
CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase is an enzyme that in humans is encoded by the ST8SIA4 gene.
NADPH oxidase organizer 1 is an enzyme that in humans is encoded by the NOXO1 gene.
Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial is an enzyme that in humans is encoded by the IDH3B gene.
NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.
Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an enzyme that in humans is encoded by the NMNAT2 gene.
Sirtuin-activating compounds (STAC) are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are caloric restriction mimetic compounds that may be helpful in treating various aging-related diseases.
Nicotinamide riboside (NR, SR647) is a pyridine-nucleoside and a form of vitamin B3. It functions as a precursor to nicotinamide adenine dinucleotide, or NAD+, through a two-step and a three-step pathway.
The Nicotinamide Ribonucleoside (NR) Uptake Permease (PnuC) Family is a family of transmembrane transporters that is part of the TOG superfamily. Close PnuC homologues are found in a wide range of Gram-negative and Gram-positive bacteria, archaea and eukaryotes.
Nicotinamide mononucleotide is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter. However, this observation has been challenged, and the matter remains unsettled.
Nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) is an enzyme that in humans is encoded by the NMNAT3 gene.
Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the SARM1 gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzymatic activity that is highly conserved from archaea, plants, nematode worms, fruit flies, and humans. In mammals, SARM1 is highly expressed in neurons, where it resides in both cell bodies and axons, and can be associated with mitochondria.
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