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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
Corresponding disease
SRPS2 short rib-polydactyly syndrome type II
Location 4q33      Physical location : 170.314.428 - 170.533.614
Synonym name
  • NimA-related protein kinase 1
  • renal carcinoma antigen NY-REN-55
  • serine/threonine-protein kinase Nek1
  • Synonym symbol(s) KIAA1901, NY-REN-55, MGC138800, DKFZp686D06121, DKFZp686K12169, SRPS2, SRTD6, SRPS2A
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 219.35 kb     34 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    GKP3 4q32.1 glycerol kinase pseudogene 3 SC4MOL 4q32-q34 sterol-C4-methyl oxidase-like CPE 4q31 carboxypeptidase E HADHAP 4q32 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase pseudogene (gastrin binding protein pseudogene) LOC285507 4q32.3 similar to chromosome 9 open reading frame 34 LOC391715 4 similar to RING finger protein 15 (Zinc finger protein RoRet) (Tripartite motif-containing protein 38) TLL1 4q32-q33 tolloid-like 1 SPOCK3 4q32.3 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3 ANXA10 4q33 annexin A10 FLJ20035 4q32.3 hypothetical protein FLJ20035 FLJ31033 4q32.3 hypothetical protein FLJ31033 LOC285510 4q32.3 similar to hypothetical protein FLJ20035 KIAA0992 4q32.3 similar to hypothetical protein FLJ20035 FLJ14431 4q32.3 hypothetical protein FLJ14431 SH3MD2 4q32.3 SH3 multiple domains 2 NEK1 4q32.3 NIMA (never in mitosis gene a)-related kinase 1 CLCN3 4q33 chloride channel 3 FLJ20534 4q33 hypothetical protein FLJ20534 LOC389241 4 similar to unactive progesterone receptor, 23 kD; likely ortholog of mouse telomerase binding protein, p23 LOC152922 4q33 similar to Methylosome subunit pICln (Chloride conductance regulatory protein ICln) (I(Cln)) (Chloride channel, nucleotide sensitive 1A) (Chloride ion current inducer protein) (ClCI) (Reticulocyte pICln) KIAA0626 4q32.3 KIAA0626 gene product AADAT 4q32.2 aminoadipate aminotransferase LOC132604 4q34.1 GalNAc transferase 10 isoform-like GALNT7 4q31.1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7 (GalNAc-T7) HMGB2 4q31 high-mobility group box 2 SAP30 4q34.1 sin3-associated polypeptide, 30kDa SCRG1 4q31-q32 sin3-associated polypeptide, 30kDa LOC391716 4 similar to 60S ribosomal protein L5 LOC389242 4 LOC389242 HAND2 4q33 heart and neural crest derivatives expressed 2 FLJ11539 4q34.1 hypothetical protein FLJ11539 MORF4 4q33-q34.1 mortality factor 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    36 - 5695 - 1286 - 2011 21211617
    34 - 5689 142.7 1258 - 2011 21211617
    36 - 5557 - 1214 - 2011 21211617
    35 - 5563 - 1242 - 2011 21211617
    33 - 5404 - 1189 - 2011 21211617
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Nervousbrain    
    Reproductivefemale systemovary   
     male systemprostate   
     male systemtestis   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelial    
    cell lineage germ cells
    cell lines renal cell carcinoma
    fluid/secretion
    at STAGE
    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
  • 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