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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
Location 17q21.33      Physical location : 49.230.919 - 49.239.450
Synonym name
  • tumor metastasis suppressor
  • nucleoside-diphosphate kinase 1
  • granzyme A-activated DNase
  • Synonym symbol(s) NDPK, NM23-H1, NM23, AWD, GAAD, NDPKA, NDPK-A
    EC.number 2.7.4.6
    DNA
    TYPE functioning gene
    STRUCTURE 8.61 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked Y status confirmed
    Map cen - 5' - NME1 - D17S396 - NME2 - 3' - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1031 - 177 - 2008 18635542
  • NME1IA
  • isoform soluble
  • 5 - 811 - 152 - 2008 18635542
  • NME1IB
  • associated with the soluble as well as membranous fraction
  • - - - - - - 2008 18635542
    mitochondrial isoform ,in the pancreatic beta cell mitochondrial subfraction
    - splicing - - - - - 24811176
  • only NME1L interacts with IKBKB
  • is a potent antimetastatic protein and may be a useful weapon in the fight against cancers
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
     pharynx   highly
     salivary gland   highly
    Reproductivefemale systembreastmammary gland highly
    Skin/Tegumentskin   highly
    Visualeye   highly
    cell lineage
    cell lines lung carcinoma cell lines
    fluid/secretion
    at STAGE
    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