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FLASH GENE
Symbol NAMPT contributors: mct - updated : 11-10-2015
HGNC name nicotinamide phosphoribosyltransferase
HGNC id 30092
Location 7q22.3      Physical location : 105.888.733 - 105.925.638
Synonym name
  • NAmPRTase
  • visfatin
  • pre-B-cell colony enhancing factor 1
  • Synonym symbol(s) PBEF, VF, MGC117256, PBEF1, DKFZp666B131, 1110035O14Rik, VISFATIN
    EC.number 2.4.2.12
    DNA
    TYPE functioning gene
    STRUCTURE 36.91 kb     11 Exon(s)
    regulatory sequence Promoter
    text structure three putative, highly conserved, E-box sequences (CACGTG) in the promoter (readily activated by CLOCK:BMAL1 through the E-boxes ) (Nakahata 2009)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 4593 - 491 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
     vessel   moderately
    Digestiveliver   moderately
     pancreas exocrine   highly Homo sapiensFetal
    Endocrinepancreas     Homo sapiensFetal
    Lymphoid/Immunespleen   highly
     thymus   moderately
    Nervousnerve   moderately
    Respiratorylung   highly
     respiratory tracttrachea  highly
     respiratory tractlarynx  moderately
    Urinarybladder   highly
     kidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal
    Text membranes
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to rattus Pbef1 (95.11 pc)
    homolog to murine Pbef1 (95.11 pc)
    Homologene
    FAMILY
  • NAPRTase family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • highly expressed in visceral fat and serum levels of the protein correlate with obesity
  • basic FUNCTION
  • catalyzing the condensation of nicotinamide with 5- phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD
  • central role in the mechanism of infection-induced preterm birth
  • may play a role in glucose homeostasis
  • essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia (Skokowa 2009)
  • playing a crucial rolein myeloid differentiation (Skokowa 2009)
  • required to modulate circadian gene expression (Nakahata 2009)
  • promoting vascular smooth muscle cell maturation and inhibiting neutrophil apoptosis
  • activating insulin receptor and has insulin-mimetic effects, lowering blood glucose and improving insulin sensitivity
  • longevity protein that adds stress-resistant life to smooth muscle cells by optimizing SIRT-mediated TP53 degradation (Van der Veer 2007)
  • proinflammatory marker of adipose tissue associated with systemic insulin resistance and hyperlipidemia (Chang 2010)
  • stimulating expression of IL-8, IL-16 and CCR3, having thus a role in the pathogenesis of acute lung injury and other inflammatory disorders (Liu 2009)
  • direct contributor to vascular inflammation (Romacho 2009
  • cytokine linked to the events of human labour initiation
  • is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair, contributing to the acceleration of cellular senescence
  • NAMPT secreted from cardiomyocytes promotes development of cardiac hypertrophy and adverse ventricular remodeling
  • enzymatically active extracellular NAMPT is secreted by human islets, is regulated by glucose and requires membrane depolarization )
  • osteogenic differentiation correlates with intracellular NAD metabolism in which NAMPT plays a regulatory role
  • role of endogenous NAMPT activity as an adaptive, protective response to an inflammatory milieu that differs from the proinflammatory activity of exogenous NAMPT
  • NAMPT-mediated NAD(+) biosynthesis is a mediator of age-associated functional declines in Neural stem/progenitor cell (NSPC)
  • rate-limiting enzyme in the NAD+ salvage pathway, playing an important role in controlling the level of NAD+ and the activity of SIRT1 in the heart and the cardiomyocytes
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development , immunity/defense
    text adipose tissue development
    PATHWAY
    metabolism cofactor , energetic
    signaling signal transduction
  • NAD biosynthesis
  • role of NAMPT/NAD+/SIRT1 pathway in the regulation of GADD45A expression by controlling the acetylation levels of FOXO3
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inverse relationship between NAMPT expression and the regulation of GADD45A gene
  • NAMPT antagonized COL1A2 promoter repression by RFX5
  • NR1D1 is a new intracellular regulator of glucagon secretion via AMPK/NAMPT/SIRT1 pathway
  • protects the heart from ischemia and reperfusion injury by stimulating SIRT1
  • NCOA6 stimulates insulin secretion likely, at least partially, by modulating NAMPT expression in pancreatic beta-cells
  • cell & other
    REGULATION
    induced by HIF1A
    inhibited by FK866
    the small molecule GMX1778, blocking the production of NAD+, resulting in tumor cell death (Watson 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in infected fetal membrane
    constitutional     --low  
    during neutrophil activation and acts as an antiapoptotic factor for neutrophils in clinical and experimental sepsis (Skokowa 2009)
    constitutional     --over  
    elevated expression in serum of maintenance haemodialysis patients correlating inversely with circulating HDL cholesterol (Nüsken 2009)
    constitutional     --over  
    in diabetics and in chronic kidney disease patients
    Susceptibility to development of obesity or Type2 diabetes mellitus (minor role)
    Variant & Polymorphism SNP
  • a rare SNP is protective from obesity (Blakemore 2009)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NAMPT inhibitors as more efficient drugs against cancer
    ANIMAL & CELL MODELS
  • mice lacking Nampt in forebrain excitatory neurons showed hippocampal and cortical atrophy, astrogliosis, microgliosis, and abnormal CA1 dendritic morphology by 2-3 months of age
  • transcript levels of Nampt were decreased in islets of NCOA6+/- mice compared with NCOA6+/+ mice
  • Nampt mRNA and protein were increased in the kidneys of rats with streptozotocin-induced diabetes