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FLASH GENE
Symbol NMNAT2 contributors: mct - updated : 05-10-2016
HGNC name nicotinamide nucleotide adenylyltransferase 2
HGNC id 16789
DNA
TYPE functioning gene
STRUCTURE 170.26 kb     12 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 initiation site 5579 34.4 307 - 2002 12359228
11 initiation site 5467 34 302 - 2002 12359228
  • having a different, inframe 5' end exon compared to variant 1
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Endocrinepancreas     Homo sapiens
    Hearing/Equilibriumearinnercochlea  
    Nervousbraindiencephalonamygdala specific Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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