serine/threonine protein kinase WNK3; protein kinase lysine-deficient 3; protein kinase with no lysine 3 (WNK3, KIAA1566, PRKWNK3)
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Function
- serine/threonine protein kinase
- role in regulation of electrolyte homeostasis, cell signaling, cell survival & cell proliferation
- activator of Na+-coupled chloride cotransporters
- inhibitor of K+-coupled chloride cotransporters
- phosphorylates WNK4
- regulates the phosphorylation of SLC12A1 & SLC12A2
- increases Ca+2 influx mediated by TRPV5 & TRPV6 by enhancing their membrane presence via a kinase-dependent pathway
- inhibits activity of KCNJ1 by decreasing its expression at the plasma membrane (non-catalytic)
- isoform 1
- isoforms 2, 3 & 4
- activation requires autophosphorylation of Ser-308
- phosphorylation of Ser-304 also promotes increased activity (putative)
- kinase activity is inhibited by WNK4
- interacts with WNK1 & WNK4
Structure
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily
- contains 1 protein kinase domain
Compartment
Alternative splicing
named isoforms=4
Expression
- expressed in brain, lung, kidney, liver & pancreas
- expressed in fetal tissues including placenta, fetal brain, lung & kidney
- very low levels of expression in fetal heart, thymus, liver & spleen
isoform 1 is brain-specific
- isoform 3 is kidney-specific
Notes
- Cys-176 is present instead of the conserved Lys in the kinase domain
- Lys-159 appears to fulfill the required catalytic function