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FLASH GENE
Symbol NEK8 contributors: mct/npt - updated : 26-06-2019
HGNC name NIMA (never in mitosis gene a)- related kinase 8
HGNC id 13387
DNA
TYPE functioning gene
STRUCTURE 13.95 kb     15 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
15 - 2858 75 692 - 2017 27892797
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Urinarykidneytubulecollecting duct highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
Homologene
FAMILY
  • protein kinase superfamily
  • NEK Ser/Thr protein kinase family
  • NIMA subfamily
    • CATEGORY
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • localized to the proximal segment of primary cilia of collecting tubules and collecting ducts, with weak cytosolic (Sohara 2008)
    • basic FUNCTION
  • may play a role in cell cycle progression from G2 to M phase
  • ciliary localization of NEK8 in a subset of ureteric-bud-derived kidney tubules is essential for maintaining the integrity of those tubules in the mammalian kidney (Trapp 2008)
  • with PKD1 function in a common pathway to regulate cystogenesis (Natoli 2008)
  • induction of ciliogenesis upon cell cycle exit is accompanied by both activation and proteasomal degradation of NEK8, and activation is dependent upon phosphorylation within the catalytic domain
  • NEK8 and NPHP4 co-operated to control TAZ activity
  • is a key effector of the ATR-mediated replication stress response
  • is a critical component of the DNA damage response that links replication stress with cystic kidney disorders
  • is involved in cytoskeleton, cilia, and DNA damage response/repair
  • is required for efficient DNA damage-induced RAD51 foci formation
  • NEK8 plays a critical role in replication fork stability through its regulation of the DNA repair and replication fork protection protein RAD51
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the signal transduction pathways of the polycystins and may control the targeting of these ciliary proteins (Sohara 2008)
  • INVS is essential for the compartmental localization of NPHP3 and NEK8, whereas localization of INVS does not require NPHP3 or NEK8
  • controls TAZ activity by a distinct mechanism; directly interacted with TAZ and induced nuclear translocation of the TAZ/NPHP9 protein complex
  • NPHP4, by inhibiting TAZ phosphorylation at the 14-3-3 binding site, leads to the tandem nuclear accumulation of TAZ and NEK8
  • NEK8 may be a new HIF target gene and VHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells
  • INVS and NPHP3 cooperate and promote ANKS6 phosphorylation by NEK8 in renal cilia
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) NPHP9 , RHPD2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in primary human breast tumors Bowers 2004)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • kidneys of Nek8 mutant mice accumulate DNA damage