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FLASH GENE
Symbol NAE1 contributors: mct/npt - updated : 25-01-2023
HGNC name NEDD8 activating enzyme E1 subunit 1
HGNC id 621
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systemuteruscervix highly
 male systemtestis  highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to Arabidosis AXR1
homolog to ubiquitin-activating enzyme 1 (N terminal region)
Homologene
FAMILY
  • Thif family (bacterial)
  • ubiquitin-activating E1 family
  • ULA1 subfamily
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • amyloid precursor protein (APP) binding protein, that is the regulatory subunit of the activating enzyme for the small ubiquitin-like protein NEDD8
  • drives the S- to M-phase transition in dividing cells, and causes apoptosis in neurons
  • NAE1 is essential for development, maintenance, and outgrowth of neuronal spines
  • contributes to the neurogenesis induced by transient ischemia and reperfusion
  • role of NEDD8-dependent ERBB2 neddylation promotes tumor growth in breast cancer
  • CELLULAR PROCESS protein
    PHYSIOLOGICAL PROCESS
    text ubiquitin mediated proteolysis
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • complex with APP and histone acetyltransferase (Tip60)
  • component of an E1 (ubiquitin-activating enzyme) like complex consisting of APPB1 and UBE1C
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to the COOH-terminal 31 amino acids of APP (C31) and colocalizes with APP in a lipid-enriched fraction called lipid rafts
  • interaction with TRIP12
  • binds to the carboxyl terminus of APP
  • DYRK2 promotes neddylation through forming a complex with NAE1, which is a component of NEDD8-activating enzyme E1, and maintaining its protein level by suppressing polyubiquitylation
  • ERBB2 directly interacts with NEDD8 and NAE1, whereas ERBB2 protein expression is decreased by neddylation depletion
  • cell & other
    REGULATION
    Other degraded by ubiquitin-dependent proteolysis
    ASSOCIATED DISORDERS
    corresponding disease(s) NAE1D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in lipid rafts observed in the Alzheimer's disease brain
    constitutional   deletion    
    resulted in dysregulation of cell cycle-regulatory genes and blockade of cardiomyocyte proliferation
    constitutional       loss of function
    disrupts transverse tubule formation, inhibits physiological hypertrophy, and represses fetal-to-adult isoform switching, thus culminating in cardiomyocyte immaturation
    constitutional   deletion    
    deletion of NAE1, the subunit of only E1 enzymes, led to complete failure of myotube formation
    tumoral     --over  
    NAE1 and UBE2M, two critical components of the neddylation pathway, were much higher in Osteosarcoma tissues and cells than in normal osseous tissues and cells
    tumoral     --over  
    in colorectal cancer, the elevated expression of NAE1 correlates with cancer progression and poor prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking Nae1 developed myocardial hypoplasia, ventricular noncompaction, and heart failure at late gestation, which led to perinatal lethality