Nicotinamide phosphoribosyltransferase

Function

Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity).

Classification

Family (Pfam)

PF18127 NAMPT_N, PF04095 NAPRTase

InterPro

Aldolase_TIM, DUF5598, N/Namide_PRibTrfase, Nicotinamide_PRibTrfase, Nicotinate_pribotase-like_C

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 84

• 2E5B X-ray 2.00A
• 2E5C X-ray 2.20A
• 2E5D X-ray 2.00A
• 2GVG X-ray 2.20A
• 2GVJ X-ray 2.10A
• 3DGR X-ray 2.10A
• 3DHD X-ray 2.00A
• 3DHF X-ray 1.80A
• 3DKJ X-ray 2.00A
• 3DKL X-ray 1.89A
• 4JNM X-ray 2.20A
• 4JR5 X-ray 1.91A
• … and 72 more

A predicted model is available from AlphaFold.

Gene Ontology · 20

• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005759 mitochondrial matrix
• GO:0005634 nucleus
• GO:0005125 cytokine activity
• GO:0042802 identical protein binding
• GO:0047280 nicotinamide phosphoribosyltransferase activity
• GO:0007267 cell-cell signaling
• GO:0032922 circadian regulation of gene expression
• GO:0006954 inflammatory response
• GO:0009435 NAD+ biosynthetic process
• GO:0034355 NAD+ biosynthetic process via the salvage pathway
• GO:0006741 NADP+ biosynthetic process
• GO:1901847 nicotinate metabolic process
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:0008284 positive regulation of cell population proliferation
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0010628 positive regulation of gene expression
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0007165 signal transduction

Drugs targeting this protein · 2

• TEGLARINAD CHLORIDE inhibitor
• DAPORINAD inhibitor

Related proteins · sequence + function similarity

• Nicotinamide phosphoribosyltransferase 1.00
• Nicotinamide phosphoribosyltransferase 0.99
• Nicotinamide phosphoribosyltransferase 0.99
• Fumarate hydratase class I, anaerobic 0.73
• Fumarate hydratase class I, aerobic 0.73
• Fumarate hydratase class I, aerobic 0.72
• Fumarate hydratase class I, aerobic 0.72
• Pyrophosphate--fructose 6-phosphate 1-phosphotransferase subunit beta 1 0.72
• Nicotinamide phosphoribosyltransferase 0.72
• Fumarate hydratase class I, aerobic 0.72
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.72
• Pyrophosphate--fructose 6-phosphate 1-phosphotransferase subunit beta 0.71

Co-cited proteins · studied together in the literature

• Nicotinamide phosphoribosyltransferase 1 shared papers

Literature · 15 cited papers

• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Visfatin as a novel mediator released by inflamed human endothelial cells. PLoS ONE · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu. Rev. Nutr. · 2012
• Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features. Mol. Cell. Proteomics · 2012
• Visfatin is secreted into the breast milk and is correlated with weight changes of the infant after the birth. Diabetes Res. Clin. Pract. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• The consensus coding sequences of human breast and colorectal cancers. Science · 2006
• Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat. Struct. Mol. Biol. · 2006
• Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 3 more in the literature graph