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Symbol NEK2 contributors: mct/ - updated : 22-01-2016
HGNC name NIMA (never in mitosis gene a)-related kinase 2
HGNC id 7745
Corresponding disease
RP67 retinitis pigmentosa 67
Location 1q32.3      Physical location : 211.836.121 - 211.848.967
Synonym name NIMA-related kinase 2
Synonym symbol(s) NLK1, HsPK 21, NEK2A
TYPE functioning gene
STRUCTURE 17.37 kb     8 Exon(s)    3 Copie(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D1S491 - D1S245 - D1S414 - NEK2 - D1S2810 - D1S505 - D1S217 - D1S237 - D1S474 - qter
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
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemprostate   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    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
  • leucine zipper dimerization motif
  • conjugated PhosphoP
    mono polymer homomer , heteromer , dimer
    interspecies ortholog to murine Nek2
    homolog to Drosophila Nek2
    homolog to C.elegans ZC581.1
  • protein kinase superfamily
  • NEK Ser/Thr protein kinase family
  • NIMA subfamily
  • CATEGORY enzyme , regulatory , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
  • 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
  • regulation of mitosis
  • regulation of cell cycle
    a component
    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
    corresponding disease(s) RP67
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    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
    Variant & Polymorphism
    Candidate gene
  • novel potential biomarker for diagnosis of breast cancer
  • Therapy target
    useful therapeutic molecular target for the treatment of breast carcinoma both in ER-positive and ER-negative cases
    inhibition mechanism of NEK2 kinase may contribute to the development of a novel type of anti-cancer drugs
    possible therapeutic target for human breast cancer especially for breast ductal carcinoma in situ