Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L. Interacts with the C-terminal region of KCNJ1. Interacts with WNK1 and WNK3. Expressed in kidney, colon and skin. Activation requires autophosphorylation of Ser- 335. Phosphorylation of Ser-331 also promotes increased activity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: EC 18.104.22.168; Protein kinase, Ser/Thr (non-receptor); Protein kinase, Other; Kinase, protein; Other group; Wnk family
Cellular Component: tight junction; cytoplasm
Molecular Function: protein serine/threonine kinase activity; protein binding; chloride channel inhibitor activity; ATP binding
Biological Process: protein localization; ion homeostasis; regulation of cellular process; ion transport; chloride transport; protein amino acid phosphorylation
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.