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FLASH GENE
Symbol NEK9 contributors: mct/pgu - updated : 01-06-2016
HGNC name NIMA (never in mitosis gene a)- related kinase 9
HGNC id 18591
Corresponding disease
LCCSR lethal congenital contracture with short ribs
Location 14q24.3      Physical location : 75.548.818 - 75.593.778
Synonym name
  • Never In Mitosis, gene A (NIMA)-related kinase Nek8
  • NIMA-related kinase 8
  • Nercc1 kinase
    • Synonym symbol(s) NERCC, NERCC1, MGC16714, DKFZp434D0935, KIAA1995, MGC138306
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 44.96 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 5560 107 979 - 2003 12840024
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Lymphoid/Immunespleen    
     thymus    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal catalytic domain homologous to the NEK family of protein kinases, protein kinase domain (52-308)
  • a nuclear localization signal (306-330)
  • central RCC1-like domain (388-726)
  • a NEK6 interaction region (732-891)
  • a guanine nucleotide exchange factor for the GTPase Ran
  • a C-terminal coiled-coil domain, AAs(941-979) are necessary not only for interaction with DYNLL1, but also for NEK6 binding to NEK9
    • conjugated PhosphoP
    mono polymer homomer , dimer , oligo
    HOMOLOGY
    interspecies ortholog to murine Nek9
    homolog to Drosophila CG10951
    ortholog to C.elegans nekl-1
    intraspecies paralog to NEK2
    Homologene
    FAMILY
  • protein kinase superfamily
  • NEK Ser/Thr protein kinase family
  • NIMA subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • primarily cytoplasmic with a small portion located in the nucleus
  • localized to the spindle poles at the metaphase stages and associated with the midbody at anaphase or telophase stage in both meiotic oocytes and the first mitotic embyros
    • basic FUNCTION
  • having a serine/threonine kinase activity and tyrosine kinase activity
  • playing a role in association with BICD2 in cell cycle independent microtubule dynamics
  • function as a mitotic regulator required for accurate spindle assembly and cell cycle progression, and is recruited to the centrosome in its phosphorylated active form
  • serine/threonine kinase that functions as an important regulator of cell-cycle and checkpoint control and is a member of a larger family of NEK proteins that share moderate conservation
  • is involved in regulating spindle organization, chromosome alignment, cytokinesis and normal cell cycle progression
  • play important roles at the G2-M transition in nuclear envelope breakdown and centromere separation
  • regulating chromosome alignment and segregation in mitosis
  • tumor associated gene, may be involved in G(2)/M progression
  • NIMA-related kinases essential for proper mitotic progression
  • role of KIF11, PLK1 and the NIMA-family kinases NEK7 and NEK9 in the control of centrosome separation and normal mitotic progression
  • NEK2, NEK6, NEK7 and NEK9 contribute to the establishment of the microtubule-based mitotic spindle, whereas NEK1, NEK10 and NEK11 have been implicated in the DNA damage response
  • play a role in spindle assembly and in the control of centrosome separation
  • is a crucial regulator of cell-cycle progression in TP53-inactivated cancer cells
  • mitotic spindle assembly requires the regulated activities of protein kinases such as NEK7 and NEK9
  • is a potential regulator of follicular homeostasis
    • CELLULAR PROCESS cell cycle, progression
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    with NEK7 and NEK6 are components of a mitotic spindle-signaling cascade
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • Mn2+
  • ATP
  • Mg2+
    • protein
  • binding to BICD2, NEK6, Ran GTPase, CDC2
  • interaction with NEK6 representing a new signaling pathway that regulates mitotic progression
  • interacting partner of NEK6 (phosphorylate NEK6 at S206 within its activation loop)
  • potentially as an active enzymatic partner of SSRP1, mediates certain SSRP1-associated cellular processes, which are ultimately essential for interphase progression
  • binds to DYNLL1, a highly conserved protein originally described as a component of the dynein complex (binding interferes with the interaction of NEK9 with its downstream partner NEK6 as well as with NEK6 activation, thus controlling both processes)
  • DYNLL1 is not absolutely required for NEK9 autoactivation, but binding to NEK9 increases the efficiency of this process
  • DYNLL1 binding to NEK9 was regulated by NEK9 autophosphorylation on Ser(944), a AA immediately located N-terminal to the DYNLL1 conserved (K/R)xTQT binding motif
  • novel NEK9 network regulates the growth of cancer cells lacking functional TP53
  • NEK9 modulate interphase progression via its association with the FACT (Facilitates Chromatin Transcription) complex (pMID: 26908619)
    • cell & other
    REGULATION
    activated by autoactivation by phosphorylation/ATP
    Other regulated by E1A (Adenovirus E1A proteins direct subcellular redistribution of NEK9)
    ASSOCIATED DISORDERS
    corresponding disease(s) LCCSR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    overexpressed in primary breast tumors
    constitutional somatic mutation      
    in NC (Nevus Comedonicus) disrupt normal follicular differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NEK9 inhibition represents a novel anti-cancer strategy by induction of mitotic catastrophe via impairment of spindle dynamics, cytokinesis and mitotic checkpoint control
    ANIMAL & CELL MODELS