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FLASH GENE
Symbol NEK1 contributors: mct - updated : 30-05-2015
HGNC name NIMA (never in mitosis gene a)-related kinase 1
HGNC id 7744
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an N terminal protein kinase domain, most similar to the catalytic domain of NIMA
  • a long basic C terminus (ATP binding and activity site)
  • contains functional nuclear localization signals, and is exported from the nucleus via a nuclear export signal-dependent pathway
  • HOMOLOGY
    interspecies homolog to rattus Nek1 (82.4 pc)
    homolog to murine Nek1 (82.9 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr family of protein kinases
  • NIMA subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    text
  • associated with the centrosomes and translocates from the nucleus during mitosis to the basal body, initiating cilia formation
  • accumulates on the chromatin during normal DNA replication
  • localize near centrosomes and play a role in centrosomal stability and ciliogenesis
  • basic FUNCTION
  • phosphorylation of serines and threonine and having a tyrosine kinase activity
  • implicated in the control of meiosis
  • may function as a kinase early in the DNA damage response pathway
  • involved in cilium control
  • CLASP2 and NEK1 proteins are present in a centrosomal complex and participate in cell cycle and cell division mechanisms
  • is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage
  • serine/threonine kinase with proposed function in DNA double-strand repair, neuronal development, and coordination of cell-cycle-associated ciliogenesis
  • involved early in a DNA damage sensing/repair pathway
  • functions independently of canonical DNA damage responses requiring the PI3 kinase-like proteins ATM and ATR
  • important for proper checkpoint control
  • 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
  • ATR-associated kinase, NEK1, enhances the stability and activity of ATR–ATRIP before DNA damage, priming ATR–ATRIP for a robust DNA damage response
  • required for the phosphorylation of multiple signaling proteins along the ATR pathway, suggesting a role of NEK1 in the initiation of ATR response
  • function of NEK1 in DNA damage signaling is critical in specific tissues
  • regulate DNA damage response, centrosome duplication and primary cilium formation
  • CELLULAR PROCESS cell cycle,division,meiosis
    PHYSIOLOGICAL PROCESS reproduction/sex
    text cell cycle regulation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • ATP
  • Mg2+
  • protein
  • binding to SPERT
  • direct interaction between NEK1 and VDAC1 providing a mechanism to explain how NEK1 prevents excessive cell death, as well as the first direct evidence that a specific kinase regulates VDAC1 activity
  • NEK1 phosphorylates WWTR1 at a site essential for the ubiquitination and proteasomal degradation of PKD2
  • interaction between FKBP6 and the NIMA-related kinase-1, NEK1, and NEK1 is a possible kinase involved in cohesin redistribution in spermatocytes
  • possible regulation of VHL by NEK1 that may contribute to ciliary homeostasis and cystogenesis
  • NEK1, is critical for initiating the ATR response, and ability of NEK1 to promote ATR activation relies on the kinase activity of NEK1 and its interaction with ATR–ATRIP
  • is required for efficient CHEK1 activation in human cells
  • NEK1 may facilitate S-phase progression by interacting with XRCC5 and regulating chromatin loading of replication factors
  • CFAP410 interact with NEK1
  • role for NEK1 in the regulation of WAPL loading during meiotic prophase I, via an interaction between NEK1 and PDS5B
  • NEK1 phosphorylates PPP1CC, leading to the dephosphorylation of WAPL, which, in turn, results in its retention on chromosome cores to promote loss of cohesion at the end of prophase I in mammals
  • NEK1 competes for binding to CEP104 with the distal centriole-capping protein CCP110
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SRPS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    severely reduces cilia number and alters ciliar morphology
    constitutional       loss of function
    Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mutated Nek1 display progressive polycystic kidney disease
  • Nek1 is the primary protein inactivated in kat2J mouse models of PKD