Nicotinamide phosphoribosyltransferase (NAMPT)
The protein contains 491 amino acids for an estimated molecular weight of 55521 Da.
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-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| a colorectal cancer sample; somatic mutation |
Biological Process
Aging
Cell-cell signaling
Cellular response to amyloid-beta
Cellular response to ionizing radiation
Cellular response to oxygen-glucose deprivation
Circadian regulation of gene expression
Circadian rhythm
Female pregnancy
Microglial cell activation
NAD biosynthesis via nicotinamide riboside salvage pathway
NAD biosynthetic process
NAD metabolic process
Negative regulation of autophagy
Negative regulation of cellular senescence
Neuron death
Nicotinamide metabolic process
Positive regulation of cell population proliferation
Positive regulation of nitric-oxide synthase biosynthetic process
Positive regulation of smooth muscle cell proliferation
Positive regulation of transcription by RNA polymerase II
Regulation of lung blood pressure
Response to D-galactose
Response to organic cyclic compound
Signal transduction
Small molecule metabolic process
Vitamin metabolic process
Water-soluble vitamin metabolic process
Cellular Component
Cell junction
Cytosol
Extracellular exosome
Extracellular space
Nuclear speck
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 608764
Nicotinamide phosphoribosyltransferase; nampt
Pre-b-cell colony-enhancing factor 1; pbef1
Pbef
Visfatin; vf
DESCRIPTION
The enzyme NAMPT (EC 2.4.2.12) converts nicotinamide (vitamin B3) to nicotinamide mononucleotide. NAMPT is the rate-limiting component of the nicotinamide adenine dinucleotide (NAD+) biosynthesis pathway (summary by Revollo et al., 2004).CLONING
Using a degenerate probe to screen an activated lymphocyte cDNA library, Samal et al. (1994) cloned PBEF. The 3-prime UTR of PBEF contains several TATT motifs, destabilizing sequences characteristic of cytokine messages. The deduced 473-amino acid protein has a calculated molecular mass of 52 kD. PBEF has a hydrophobic N terminus, 2 N-glycosylation sites, several putative phosphorylation sites, and 6 cysteines. Northern blot analysis detected transcripts of about 2.0, 2.4, and 4.0 kb in all tissues examined, with highest expression in liver, followed by muscle. Although PBEF lacks a typical signal sequence for secretion, transfected COS-7 and mouse embryonic fibroblasts secreted PBEF into the culture medium. Western blot analysis detected PBEF at an apparent molecular mass of 52 kD.GENE FUNCTION
Samal et al. (1994) found that recombinant PBEF secreted from transfected COS-7 and mouse embryonic fibroblasts was not itself active in a pre-B-cell colony formation assay, but it synergized the pre-B-cell colony formation activity of stem cell factor (184745) and interleukin-7 (146660). Increased activity was PBEF dose dependent. PBEF showed no effect with cells of myeloid or erythroid lineages. Expression of PBEF was induced in human peripheral blood lymphocytes by pokeweed mitogen and was superinduced by cycloheximide. It was also induced by phorbol ester treatment in a T-lymphoblastoid cell line. In neutrophils from healthy donors, Jia et al. (2004) found that PBEF1 was upregulated by IL1-beta (147720) and by lipopolysaccharide. Prevention of PBEF1 translation with an antisense oligonucleotide completely abrogated the inhibitory effects of lipopolysaccharide, IL1-beta, GMCSF (CSF2; 138960), IL8 (146930), and TNF-alpha (191160) on neutrophil apoptosis. Immunoreactive PBEF1 was detectable in culture supernatants from lipopolysaccharide-stimulated neutrophils, and a recombinant PBEF1 fusion protein inhibited neutrophil apoptosis. PBEF1 was also expressed in neutrophils from critically ill patients with sepsis and delayed apoptosis; the expression occurred at higher levels than seen in experimental inflammation, and a PBEF1 antisense oligonucleotide significantly restored the normal kinetics of apoptosis in septic polymorphonuclear neutrophils. Inhibition of apoptosis by PBEF1 was associated with reduced activity of caspase-8 (601763) and caspase-3 (600636), but not caspase-9 (602234). Jia et al. (2004) concluded that PBEF1 is an inflammatory cytokine that plays a requisite role in the delayed neutrophil apoptosis of sepsis. Revollo et al. (2004) identified NAMPT as the rate-limiting component in the mammalian NAD biosynthesis pathway. Increased doses of Nampt, but not Nmnat1 (608700), increased total cellular NAD and enhanced the transcriptional regulatory activity of the catalytic domain of Sirt1 (604479) in mouse fibroblasts. Revollo et al. (2004) concluded that NAD biosynthesis mediated by NAMPT regulates the function of SIRT1. Fukuhara et al. (2005) isolated visfatin, an adipocytokine highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increased during development of obesity. Visfatin corresponds to PBEF, a ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608764 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed