WNK4 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; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Wnk family
Chromosomal Location of Human Ortholog: 17q21.2
Cellular Component:  bicellular tight junction; cytosol; membrane
Molecular Function:  ATP binding; chloride channel inhibitor activity; protein binding; protein serine/threonine kinase activity
Biological Process:  chloride transport; distal tubule morphogenesis; intracellular signal transduction; ion homeostasis; ion transport; negative regulation of pancreatic juice secretion; negative regulation of sodium ion transport; protein localization; protein phosphorylation; regulation of cellular process; renal sodium ion absorption
Disease: Pseudohypoaldosteronism, Type Iib
Reference #:  Q96J92 (UniProtKB)
Alt. Names/Synonyms: PHA2B; PRKWNK4; Protein kinase lysine-deficient 4; Protein kinase with no lysine 4; Serine/threonine-protein kinase WNK4; WNK lysine deficient protein kinase 4; WNK4
Gene Symbols: WNK4
Molecular weight: 134,739 Da
Basal Isoelectric point: 5.36  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene