Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol WNK3 contributors: mct - updated : 15-06-2014
HGNC name WNK lysine deficient protein kinase 3
HGNC id 14543
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