PDB rendering based on 2g95.
|Symbols||; 1110035O14Rik; PBEF; PBEF1; VF; VISFATIN|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the PBEF1 gene. This protein has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits neutrophil apoptosis.
Expression & Regulation
NAMPT is downregulated by an increase of miR-34a in obesity via a 3'UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased SIRT1 activity.
- nicotinamide D-ribonucleotide + diphosphate nicotinamide + 5-phospho-alpha-D-ribose 1-diphosphate
NAmPRTase catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, one step in the biosynthesis of nicotinamide adenine dinucleotide. The protein is an adipokine that is localized to the bloodstream and has various functions, including the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also activates insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity. The protein is highly expressed in visceral fat and serum levels of the protein correlate with obesity. This gene has a pseudogene on chromosome 10.
The systematic name of this enzyme class is nicotinamide-nucleotide:diphosphate phospho-alpha-D-ribosyltransferase. Other names in common use include:
- NMN pyrophosphorylase,
- nicotinamide mononucleotide pyrophosphorylase,
- nicotinamide mononucleotide synthetase, and
- NMN synthetase.
Nampt/PBEF/visfatin was originally cloned as a putative cytokine shown to enhance the maturation of B cell precursors in the presence of Interleukin-7 (IL-7) and stem cell factor, it was therefore named “pre-B cell colony-enhancing factor” (PBEF). When the gene encoding the bacterial nicotinamide phosphoribosyltransferase (nadV) was first isolated in Haemophilus ducreyi, it was found to exhibit significant homology to the mammalian PBEF gene. Rongvaux et al. demonstrated genetically that the mouse PBEF gene conferred Nampt enzymatic activity and NAD-independent growth to bacteria lacking nadV. Revollo et al. determined biochemically that the mouse PBEF gene product encodes a Nampt enzyme, capable of modulating intracellular NAD levels. Others have since confirmed these findings. More recently, several groups have reported the crystal structure of Nampt/PBEF/visfatin and they all show that this protein is a dimeric type II phosphoribosyltransferase enzyme involved in NAD biosynthesis.
Although the original cytokine function of PBEF has not been confirmed to date, others have since reported or suggested a cytokine-like function for this protein. In particular, Nampt/PBEF was recently re-identified as a “new visceral fat-derived hormone” named visfatin. It is reported that visfatin is enriched in the visceral fat of both humans and mice and that its plasma levels increase during the development of obesity. Noteworthy is that visfatin is reported to exert insulin-mimetic effects in cultured cells and to lower plasma glucose levels in mice by binding to and activating the insulin receptor. However, the physiological relevance of visfatin is still in question because its plasma concentration is 40 to 100-fold lower than that of insulin despite having similar receptor-binding affinity. In addition, the ability of visfatin to bind and activate the insulin-receptor has yet to be confirmed by other groups.
On 26 October 2007, A. Fukuhara (first author), I.Shimomura (senior author) and the other co-authors of the paper, who first described Visfatin as a visceral-fat derived hormone that acts by binding and activating the insulin receptor, retracted the entire paper at the suggestion of the editor of the journal 'Science' and recommendation of the Faculty Council of Osaka University Medical School after a report of the Committee for Research Integrity.
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- Choi SE, Fu T, Seok S, Kim DH, Yu E, Lee KW, Kang Y, Li X, Kemper B, Kemper JK (December 2013). "Elevated microRNA-34a in obesity reduces NAD+ levels and SIRT1 activity by directly targeting NAMPT". Aging Cell. 12 (6): 1062–72. doi:10.1111/acel.12135. PMID 23834033.
- "Entrez Gene: PBEF1 pre-B-cell colony enhancing factor 1".
- Martin PR, Shea RJ, Mulks MH (February 2001). "Identification of a plasmid-encoded gene from Haemophilus ducreyi which confers NAD independence". J. Bacteriol. 183 (4): 1168–74. doi:10.1128/JB.183.4.1168-1174.2001. PMC 94989. PMID 11157928.
- Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F (November 2002). "Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis". Eur. J. Immunol. 32 (11): 3225–34. doi:10.1002/1521-4141(200211)32:11<3225::AID-IMMU3225>3.0.CO;2-L. PMID 12555668.
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- van der Veer E, Nong Z, O'Neil C, Urquhart B, Freeman D, Pickering JG (July 2005). "Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation". Circ. Res. 97 (1): 25–34. doi:10.1161/01.RES.0000173298.38808.27. PMID 15947248.
- Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C (July 2006). "Structure of Nampt/PBEF/visfatin, a mammalian NAD+ biosynthetic enzyme". Nat. Struct. Mol. Biol. 13 (7): 661–2. doi:10.1038/nsmb1114. PMID 16783373.
- Kim MK, Lee JH, Kim H, Park SJ, Kim SH, Kang GB, Lee YS, Kim JB, Kim KK, Suh SW, Eom SH (September 2006). "Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866". J. Mol. Biol. 362 (1): 66–77. doi:10.1016/j.jmb.2006.06.082. PMID 16901503.
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- van der Veer E, Nong Z, O'Neil C et al. (2005). "Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation". Circ. Res. 97 (1): 25–34. doi:10.1161/01.RES.0000173298.38808.27. PMID 15947248.
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- visfatin, human at the US National Library of Medicine Medical Subject Headings (MeSH)
- NAMPT human gene location in the UCSC Genome Browser.
- NAMPT human gene details in the UCSC Genome Browser.