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FLASH GENE
Symbol WNK2 contributors: mct - updated : 15-06-2011
HGNC name WNK lysine deficient protein kinase 2
HGNC id 14542
Location 9q22.31      Physical location : 95.947.211 - 96.082.853
Genatlas name [with-no-K(Lys)] kinases lysine deficient protein kinase 2
Synonym name
  • mitogen-activated protein kinase kinase kinase
  • serogically defined colon cancer antigen 43
  • antigen NY-CO-433
  • protein kinase, lysine deficient 2
  • Synonym symbol(s) PRKWNK2, NY-CO43, SDCAG43, RP11-165J3.2, KIAA1760, P/OKcl.13
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 135.64 kb     29 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 6834 - 2217 - 2001 11571656
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveintestinesmall intestine    Homo sapiensAdult
     intestinelarge intestinecolon   Homo sapiensAdult
    Nervousbrain   predominantly Homo sapiens
     brainforebraincerebral cortex highly Homo sapiens
     brainlimbic systemhippocampus   Homo sapiens
     braindiencephalonthalamus   Homo sapiens
    Olfactory (smell)olfactory bulb     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatum    Homo sapiensAdult
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    NervousPurkinje cell Homo sapiens
    Nervouspyramidal cell Homo sapiens
    cell lineage
    cell lines various cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • in neocortical pyramidal cells, thalamic relay cells, and cerebellar granule and Purkinje cells in the developing brain
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a small N-terminal domain followed by a kinase domain
  • a cysteine in place of a lysine in catalytic subdomain II
  • the WNK kinase sequence signature within the subdomains I and II
  • regulatory C-terminal including a highly conserved acidic motif and two coil-coil domains
  • HOMOLOGY
    Homologene
    FAMILY
  • MEKK protein kinase family
  • Ser/Thr protein kinase family
  • WNK (with-no-lysine [K]) subfamily of protein kinases
  • CATEGORY enzyme , antigen , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • cytoplasmic serine-threonine kinase containing cysteine in place of the lysine found at the conserved ATP-binding location in subdomain II of protein kinases
  • involved in the modulation of growth factor-induced cancer cell proliferation through the MAP2K1/ERK1/2 pathway
  • candidate tumor suppressor gene, having potentially a coordinated activity of WNK kinases in the regulation of cell proliferation
  • cell growth regulator that modulates activation of the ERK1/2 protein kinase and is epigenetically silenced in gliomas
  • controls a RhoA-mediated cross-talk mechanism that regulates the efficiency with which MAP2K1 can activate ERK1/2 upon growth factor stimulation
  • with WNK1, WNK3, WNK4, have vital roles in the control of salt homeostasis and blood pressure
  • negatively regulate epidermal growth factor receptor signaling via inhibition of MAP2K1
  • role for WNK2 in the regulation of SLC12A2, SLC12A5 in the mammalian brain, with implications for both cell volume regulation and/or GABAergic signaling
  • might activate SLC12A2 indirectly via STK39
  • control GTP-loading of RAC1, a signalling guanosine triphosphatase involved in cell migration and motility
  • tumour-suppressing role of WNK2 that is related to RAC1 signalling and tumour cell invasion and proliferation
  • important role for WNK2 in the control of glia-derived cell migration and tumorigenic growth
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a protein complex in the mammalian brain with STK39, a known phosphoregulator of SLC12A2
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
  • protein
  • promotes Cl- accumulation by reciprocally activating SLC12A2 and inhibiting SLC12A5 in a kinase-dependent manner
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    aberrantly methylated in 83p100 and 71p100 of grade II and III meningiomas, respectively
    tumoral     --low  
    by promoter methylation in 17.5 p100 of adult gliomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS