WNK4 - definition. What is WNK4
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WNK4         
  • '''Fig. 1'''. '''Domain structure of WNK4 and the positions of the initially identified PHAII-causing mutations.''' The amino-acid (aa) positions of the domains are provided in parentheses. Some important PHAII mutations are localized in the acidic motif and calmodulin-binding domain, respectively.
  • '''Fig. 2.''' '''The WNK4-SPAK/OSR1-NCC phosphorylation cascade.''' WNK4 phosphorylates and activates SPAK/OSR1, which in turn phosphorylate and activates NCC. In this manner, WNK4 regulates sodium reabsorption in the distal convoluted tubule and downstream potassium secretion through its positive effects on NCC.
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  • '''Fig. 3. Proposed mechanisms by which PHAII-causing mutations in WNK4, KLHL3, and Cullin 3 lead to increased kinase activity of WNK4.''' ''Left panel'', under physiological condition, angiotensin II elicits an increase in intracellular Ca<sup>2+</sup>.&nbsp; Ca<sup>2+</sup> ions interact with the acidic motif of WNK4 and increase the kinase activity. Ca<sup>2+</sup>/calmodulin (CaM) also binds to the C-terminal CaM-binding domain and relieves the inhibition of the kinase activity of WNK4. WNK4 protein is degraded by the KLHL3-Cullin 3 ubiquitin E3 ligase. ''Right panel'', under PHAII condition, PHAII mutations in the acidic motif mimic the Ca<sup>2+</sup> binding state and lead to an increase in kinase activity.&nbsp; The R1185C mutation relieves the inhibitory effect of the C-terminal domain on the kinase activity of WNK4. Mutations in KLHL3 or Cullin 3 impair the degradation of WNK4 protein, leading to an increase in total kinase activity.
PROTEIN-CODING GENE IN THE SPECIES HOMO SAPIENS
WNK4 (gene)
Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.