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FLASH GENE
Symbol NEK2 contributors: mct/ - updated : 22-01-2016
HGNC name NIMA (never in mitosis gene a)-related kinase 2
HGNC id 7745
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 splicing 2161 51.8 445 . low amounts in the G(1) phase and exhibit increased abundance in the S and G(2) phases . disappearing in prometaphase-arrested cells 2005 15659651
  • inducing centrosome splitting upon overexpression
  • having a PP1-binding site (binding to catalytic subunit of protein phosphatase-1 (PP1C)
  • NEK2A
  • leucine zipper dimerization motif
  • 7 splicing 1938 44.9 384 . low amounts in the G(1) phase and exhibit increased abundance in the S and G(2) phases . remaining elevated in prometaphase-arrested cells 2005 15659651
  • also called NEK2B
  • lacking the PP1-binding site
  • leucine zipper dimerization motif
  • 8 - 1750 - 388 - 2005 15659651
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period
    cell cycle     cell cycle, checkpoint, G2M
    Text cell-cycle dependent pattern, undetectable during G1, appearing in S, reacting maximum levels in late G2, expression pattern is highly reminiscent of that of A and B cyclins
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • leucine zipper dimerization motif
  • conjugated PhosphoP
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Nek2
    homolog to Drosophila Nek2
    homolog to C.elegans ZC581.1
    Homologene
    FAMILY
  • protein kinase superfamily
  • NEK Ser/Thr protein kinase family
  • NIMA subfamily
  • CATEGORY enzyme , regulatory , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nucleus,nucleolus
    text
  • recruited to the proximal ends of centrioles through a number of mechanisms including microtubule-dependent and independent pathways and association with cytoplasmic particles
  • concentrated at the proximal ends of centrioles, and also localises to the distal portion of the mother centriole
  • basic FUNCTION
  • functioning as a serine/threonine kinase
  • playing a role at the G2-M transition
  • playing a role in meiosis
  • regulating centrosome cohesion and separation through phosphorylation of structural components of the centrosome
  • involved in biological processes of the Golgi body, perhaps in relation to the inheritance of Golgi during mitosis or to cell cycle stage-specific regulation of exocytosis
  • interacts with MXD1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling
  • NEK2-mediated phosphorylation of SGOL1 provides a link between centromeric cohesion and spindle microtubule
  • kinetochore-associated protein kinase essential for faithful chromosome segregation and regulating kinetochore microtubule attachment stability
  • increased NEK2 activity disrupts the interaction of CROCC and centrosomes, resulting in binding of beta-catenin to CROCC-independent sites on centrosomes, an event that is required for centrosome separation)
  • play a pivotal role in tumorigenic growth of breast carcinoma cells
  • may act upon the MAD2L1-CDC20 protein complex and play a critical role in regulating the mitotic checkpoint protein complex
  • involved in the phosphorylation of NDC80 that modulates chromosome alignment and signaling of the spindle assembly checkpoint
  • might bear a close relationship with development and progression of breast carcinoma
  • has a role in promoting cilium disassembly at the onset of mitosis
  • 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
  • in contrast to NEK2, KIF18A is not degraded until anaphase showing that additional mechanisms contribute to NEK2 degradation
  • CELLULAR PROCESS cell cycle,division,meiosis
    cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    text
  • regulation of mitosis
  • regulation of cell cycle
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • binding to TERF1
  • binding to the catalytic subunit of protein phosphatase-1 (PP1C)
  • phosphorylating HEC, essential for faithful segregation
  • interacting with NECAB3
  • phosphorylates SGOL1 and such phosphorylation is essential for faithful chromosome congression in mitosis
  • interacting with PCNT (its kinase activity is inhibited by addition of the NEK-binding region of PCNT in a dose-dependent manner)
  • implicated in disconnecting the centrosomes through disjoining the linker proteins CEP250 and rootletin
  • PLK1 controls the NEK2-PPP1CC antagonism in centrosome disjunction
  • recruitment of NEK2 to the proximal ends of centrioles is dependent on one of its substrates, the centrosome cohesion protein CEP250
  • CNTROB is a substrate of both NEK2 and PLK1 (NEK2 phosphorylation antagonizes the microtubule stabilizing activity of CNTROB)
  • interaction of FANCA and NEK2
  • LRRC45 interacts with both CEP250 and CROCC and is phosphorylated by NEK2 at S661 during mitosis
  • NEK2 was demonstrated to phosphorylate CEP68 and this phosphorylation appears to promote CEP68 degradation in mitosis)
  • NEK2 is found to stabilize SUFU at least partly depending on its kinase activity, thereby triggering phosphorylation of the SUFU protein
  • NEK2 stabilizes SUFU through impairing ubiquitin/proteasome degradation of SUFU
  • GLI1 and GLI2 directly bind to the promoter regions of NEK2 gene and induced its transcription
  • KIFC3 is eventually inactivated by NEK2 to enable KIF11-driven bipolar spindle assembly
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) RP67
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    aberrant regulation of Nek2 activity can lead to aneuploid defects characteristic of cancer cells
    tumoral     --over  
    in all breast carcinoma cell lines
    constitutional     --over  
    may promote aneuploidy by disrupting the control of the mitotic checkpoint
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • novel potential biomarker for diagnosis of breast cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    useful therapeutic molecular target for the treatment of breast carcinoma both in ER-positive and ER-negative cases
    cancer  
    inhibition mechanism of NEK2 kinase may contribute to the development of a novel type of anti-cancer drugs
    cancerreproductivebreast
    possible therapeutic target for human breast cancer especially for breast ductal carcinoma in situ
    ANIMAL & CELL MODELS