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. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Expressed in kidney, colon and skin. 3 alternatively spliced human isoforms have been reported. 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 mouse Ortholog: 11|11 D
Cellular Component:  bicellular tight junction; cell body; cell junction; cytoplasm; cytosol; membrane; protein-containing complex
Molecular Function:  ATP binding; chloride channel inhibitor activity; chloride ion binding; kinase activity; nucleotide binding; potassium channel inhibitor activity; protein binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process:  activation of protein kinase activity; aldosterone secretion; calcium ion homeostasis; cellular cation homeostasis; cellular chloride ion homeostasis; cellular response to xenobiotic stimulus; chloride transport; distal tubule morphogenesis; ERK1 and ERK2 cascade; gene expression; inflammatory response; intracellular signal transduction; ion homeostasis; ion transport; macrophage activation; negative regulation of pancreatic juice secretion; negative regulation of protein kinase activity; negative regulation of sodium ion transport; phosphorylation; positive regulation of potassium ion import across plasma membrane; positive regulation of sodium ion transmembrane transporter activity; potassium ion transmembrane transport; protein kinase C signaling; protein localization; protein phosphorylation; regulation of protein kinase activity; renal sodium ion absorption; response to dietary excess; response to xenobiotic stimulus; signal transduction; sodium ion transmembrane transport
Reference #:  Q80UE6 (UniProtKB)
Alt. Names/Synonyms: 2010002J11Rik; OTTMUSP00000002621; Pha2b; Prkw; Prkwnk4; Protein kinase lysine-deficient 4; Protein kinase with no lysine 4; protein kinase, lysine deficient 4; Serine/threonine-protein kinase WNK4; WNK lysine deficient protein kinase 4; Wnk4
Gene Symbols: Wnk4
Molecular weight: 132,410 Da
Basal Isoelectric point: 5.4  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene