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FLASH GENE
Symbol NMNAT2 contributors: mct - updated : 05-10-2016
HGNC name nicotinamide nucleotide adenylyltransferase 2
HGNC id 16789
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , tetramer
HOMOLOGY
intraspecies homolog to NMNAT2
Homologene
FAMILY nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme family
CATEGORY chaperone/stress , enzyme
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm,organelle,membrane
intracellular,cytoplasm,organelle,Golgi
intracellular,cytoplasm,organelle,endosome
text
  • NMNAT2 is localized to the Golgi complex
    • basic FUNCTION
  • catalyzing an essential step in NAD (NADP) biosynthetic pathway
  • brain-specific NMNAT2 delays injury-induced axon degeneration dependent on its NAD synthesis activity
  • endogenous NMNAT2 prevents spontaneous degeneration of healthy axons
  • NMNAT1, NMNAT2, NMNAT3 catalyzes the formation of nicotinamide adenine dinucleotide
  • is a neuronal protein peripherally attached to membranes via palmitoylation, suggesting that NMNAT2 is transported to synaptic terminals via an endosomal pathway
  • NMNAT2 activity supports axon survival through a site of action distinct from NMNAT2 transport vesicles and protein stability, a key determinant of axon protection, is enhanced by mutations that disrupt palmitoylation and dissociate NMNAT2 from these vesicles
  • is a critical survival factor for axons
  • NMNAT2 localisation and turnover are a valuable target for modulating axon degeneration
  • requirement for NMNAT2 in axon maintenance even during development
  • important functional role of NMNAT2 in TP53-mediated signaling
  • is a critical survival factor for axons and its constant supply from neuronal cell bodies into axons is required for axon extension
  • having a chaperone function, independent from its enzymatic activity
  • exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health
  • acts not only as a NAD synthase involved in axonal maintenance but as a molecular chaperone helping neurons to overcome protein unfolding and protein aggregation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism cofactor
    signaling
    NAD (NADP) biosynthetic pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NMNAT2 affects MAPT phosphorylation by regulating PPP2CA activity
  • NMNAT2, a NAD(+) synthetase, is a novel downstream target gene of TP53
  • NMNAT2 is a substrate for cytosolic thioesterases LYPLA1 and LYPLA2 and palmitoylation/depalmitoylation dynamics are on a time scale similar to its short half-life
  • absence of SARM1 rescues development and survival of NMNAT2-deficient axons
  • NMNAT2 complexes with heat shock protein 90 (HSP90AA1) to refold aggregated protein substrates
  • role for SKP1 as an auxiliary component of the target recognition module that enhances binding of FBXO45 to NMNAT2
    • cell & other
    REGULATION
    Other palmitoylation is necessary to target NMNAT2 to post-Golgi vesicles, thereby influencing its protein turnover and axon protective capacity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    may contribute to axon degeneration in a variety of neurodegenerative disorders
    constitutional     --low  
    during cardiac hypertrophy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    endogenous NMNAT2 represents an exciting new therapeutic target for axonal disorders
    cardiovascularcardiomyopathy 
    modulation of NMNAT2 activity may be beneficial in cardiac hypertrophy
    ANIMAL & CELL MODELS