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FLASH GENE
Symbol WNK3 contributors: mct - updated : 15-06-2014
HGNC name WNK lysine deficient protein kinase 3
HGNC id 14543
Location Xp11.22      Physical location : 54.219.257 - 54.384.438
Synonym name
  • protein kinase, lysine deficient 3
  • protein kinase with no lysine 3
  • Synonym symbol(s) PRKWNK3, KIAA1566
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 161.58 kb     24 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 7573 191.8 1743 brain isoform 2004 15194194
  • contains a short version of exon 18 (18a), and exon 22
  • acts in tandem with STK39
  • 24 - 7744 198.4 1800 brain isoform 2004 15194194
  • contains a long version of exon 18 (18b) that has an additional 47 amino acids, and exon 22
  • acts in tandem with STK39
  • 22 - - - - renal 2009 19470686
  • contains only the shorter exon 18 (18a) and lacks exon 22
  • C-terminal fragment of renal WNK3 is able to stimulate SLC12A3 expression points to key motifs within it being responsible for the stimulatory actions of WNK3
  • seems to upregulate SLC12A3 through a STK39-independent pathway
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   predominantly
    Digestiveliver    
    Nervousbrain   predominantly Homo sapiens
    Reproductivemale systemtestis   
    Urinarykidneynephron  predominantly Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a short N terminus
  • a catalytic domain containing a cysteine in place of a lysine in catalytic subdomain II
  • the WNK kinase sequence signature within the subdomain I and II, kinase domain of WNK3 alone sufficient to increase TRPV5-mediated Ca2+ transport
  • regulatory C-terminal including a highly conserved acidic motif and two coil-coil domains
  • C-terminal motifs contributed by exons 18 and 22 play an important role in the actions of WNK3 isoforms on SLC12A3 , and coiled-coil domain in the C terminus of WNK3 was important to its interaction with RBFOX1
  • HOMOLOGY
    Homologene
    FAMILY
  • With No Lysine (K) family of protein serine/threonine kinases
  • Ser/Thr family of protein kinase
  • WNK kinase family
  • CATEGORY enzyme , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytosolic
    text colocalizes with SLC12A2 and SLC12A4, SLC12A5 in diverse chlore-transporting epithelia and in neurons expressing ionotropic GABA(A) receptors in the hippocampus, cerebellum, cerebral cortex, and reticular activating system
    basic FUNCTION
  • regulating the activity of SLC12A1 and SLC12A3 transporters by altering their expression at the plasma membrane
  • implicated in NaCl, water, and blood pressure homeostasis, perhaps via signaling downstream of vasopressin
  • being part of the Cl(-)/volume-sensing mechanism necessary for the maintenance of cell volume during osmotic stress and the dynamic modulation of GABA neurotransmission
  • enhanced Ca2+ influx and Na+ current mediated by TRPV6, which is the closest homolog of TRPV5 that mediates active intestinal Ca2+ absorption
  • positive regulator of the transcellular Ca2+ transport pathway
  • with WNK2, WNK1, WNK4, have vital roles in the control of salt homeostasis and blood pressure
  • when activated, subsequently phosphorylate and activate the related protein kinases STK39 and OXSR1
  • might have a pivotal role in regulating neuronal excitability by stimulating Cl&
  • 8722; entry through SLC12A2 and inhibit Cl&
    8722; exit through the K/Cl co-transporter SLC12A5
  • increase membrane expression of SLC12A3, SLC12A2, SLC12A1 in oocytes and also to inhibit the basolateral K-Cl transporters SLC12A4, SLC12A5, SLC12A6, SLC12A7
  • an important regulator of SLC12A3 activity
  • role of WNK3 in RNA processing
  • modulates RBFOX1-mediated mRNA splicing by causing its subcellular relocalization
  • modulates the subcellular localization of RBFOX1 in a kinase activity-dependent manner
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    WNK3/STK39 pathway involved in the regulation of SLC12A1
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
  • ATP binding
  • magnesium
  • protein
  • interacting with SLC12A1, SLC12A3 (regulating the phosphorylation)
  • interacting with SLC12A4, SLC12A5, SLC12A2
  • interacts with WNK4 and WNK1 to regulate SLC12A3 in both human kidney cells and Xenopus oocytes
  • WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds RBFOX1 and inhibits its splicing activity in a kinase activity-dependent manner
  • RBFOX1 differentially binds neuronal relative to nonneuronal forms of WNK3
  • LINGO1 potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity
  • potential role for WNK3 on SLC12A3 expression at the plasma membrane, an effect apparently independent of the STK39 and the aldosterone-SGK1 pathway
  • WNK3 is an activator of SLC12A3, and NEDD4L is an inhibitor
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS