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FLASH GENE
Symbol NME1 contributors: mct/npt/pgu - updated : 20-12-2023
HGNC name non-metastatic cells 1, protein (NM23A) expressed in
HGNC id 7849
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • putative leucine-zipper domain
  • a Kpn (Drosophila Killer of prune) loop
  • a RGD domain
  • a C terminal extension preceded by the YEEEEP motifs
  • HOMOLOGY
    Homologene
    FAMILY
  • NM23 nucleoside diphosphate kinase gene family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • pyrimidine biosynthetic pathway, involved in the phosphorylation of nucleoside diphosphates
  • selectively regulates the PRKAA1, independently of the AMP concentration such that the manipulation of NME1 nucleotide trans-phosphorylation activity to generate ATP enhanced the activity of PRKAA1
  • involved in the regulation of many cellular processes as well as in tumor metastasis
  • involved in epidermal homeostasis which depends on a tight regulation of the levels of NME1 isoforms
  • can negatively regulate cell migration and tumor metastasis by modulating the activity of CDC42 and possibly other Rho family members through interaction with MCF2
  • having a 3prime-5prime exonuclease activity necessary for metastasis suppressor function
  • tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP
  • may have a role in the regulation of cell cycle and apoptosis in human B-cells
  • loss of NME1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability
  • critical for control of cell-cell adhesion and cell migration at early stages of the invasive program in epithelial cancers, orchestrating a barrier against conversion of in situ carcinoma into invasive malignancy
  • critical role for NME1 isoforms in limiting mutagenesis and suppressing UV radiation -induced melanomagenesis
  • exists in a functional cellular complex with PRKAA1 and CFTR in airway epithelia, and its catalytic function is required for the PRKAA1-dependent regulation of CFTR
  • may exert its anti-metastatic effect by blocking Ras/ERK signaling
  • NME1, NME2 have likely differential abilities to modulate tumorigenesis
  • NME1, NME5, NME7, and NME8 also exhibit a 3'-5' exonuclease activity, suggesting roles in DNA proofreading and repair
  • NME1 and, more recently, NME3, have been implicated in repair of both single- and double-stranded breaks in DNA
  • NME1 and NME2 have been identified as potential canonical transcription factors that regulate gene transcription through their DNA-binding activities
  • NME1, NME2 catalyze the transfer of gamma-phosphate from nucleoside triphosphates to nucleoside diphosphates by a ping-pong mechanism involving the formation of a high-energy phosphohistidine intermediate
  • NME1 induces transcription through its direct binding to the promoter region of a target gene
  • NME1 is required for non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs)
  • addition of NME1 or NME2 to DNM2 facilitates DNM2 oligomerization and increases GTPase activity, both required for vesicle scission
  • inhibition of cell migration and proliferation, alongside actions in apoptosis and phagocytosis are all mechanisms through which NME1 acts against metastatic progression
  • potential functional role for NME1 in neuroblastoma pathogenesis
  • NME1 is a powerful inhibitor of Epithelial-mesenchymal transition (EMT)
  • NME1, but not NME2, acts specifically to inhibit EMT and prevent the earliest stages of metastasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with SCS(succinyl-coA-synthetase)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • NME1 is a novel binding partner of the key metabolic regulator CoA, which inhibits its nucleoside diphosphate kinase activity via non-covalent and covalent interactions
  • protein
  • MEN1, SCS
  • interacting with TUBB, TUBG1, VIM
  • interaction partner of PRUNE
  • IFI16 and NME1 are simultaneously bound to the same DNA fragments, suggesting their common involvement in the reduced development of some tumors
  • TXNRD1 is an interacting protein of NME1, and it binds specifically to oxidized NME1
  • TSLP might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion
  • NME1 inhibits STAT3 signaling via a negative feedback mechanism
  • NME1 controls melanoma cell morphology via upregulation of the extracellular matrix (ECM) protein fibronectin
  • NME1/fibronectin axis represents a barrier to melanoma progression
  • important role for cytoplasmic IRF6 in regulating the availability or localization of the NME1/2 complex and thus the dynamic behavior of epithelia during lip/palate development
  • NME1 enhanced ALDOC transcription, evidenced by increased expression of ALDOC pre-mRNA and activity of an ALDOC promoter-luciferase module
  • cell & other
    REGULATION
    inhibited by of NME1 expression by TSLP was completely abrogated by STAT3 inhibitor
    Other key enzymatic and metastasis suppressor functions of NME1 are regulated by oxido-reduction of its Cys109
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    mutated in agressive neuroblastoma with a reduced expression in tumor progression to the metastatic phenotype
    tumoral     --over  
    correlated with poor neuroblastoma patient outcomes
    tumoral     --low  
    associated with aggressive forms of multiple cancers
    tumoral     --other  
    its expression is associated with poor prognosis in peripheral T-cell lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR (Fetal Growth Restrictio
  • Therapy target
    ANIMAL & CELL MODELS
  • NME1-deficient mouse embryo fibroblasts grew poorly in culture, were more sensitive to stress than WT fibroblasts, and did not immortalize, which suggested that they senesce earlier than do WT fibroblasts