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 and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition. Isoform 3: Dominant-negative regulator of the longer isoform 1. Does not have kinase activity, does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Downregulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity. In kidney, may play an important role regulating sodium and potassium balance. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and connecting tubule (CNT) of the nephron. 6 human isoforms generated by alternative promoter usage or alternative splicing have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 188.8.131.52; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Wnk family
Molecular Function: ATP binding; chloride channel inhibitor activity; kinase activity; magnesium ion binding; nucleotide binding; phosphatase binding; potassium channel inhibitor activity; protein binding; protein kinase activator activity; protein kinase activity; protein kinase binding; protein kinase inhibitor activity; protein serine/threonine kinase activity; protein serine/threonine kinase inhibitor activity; transferase activity
Biological Process: cellular response to calcium ion; cellular response to chemokine; chemokine (C-C motif) ligand 21 signaling pathway; intracellular signal transduction; ion homeostasis; ion transport; lymphocyte migration into lymph node; negative regulation of cell-cell adhesion mediated by integrin; negative regulation of GTPase activity; negative regulation of heterotypic cell-cell adhesion; negative regulation of kinase activity; negative regulation of leukocyte cell-cell adhesion; negative regulation of pancreatic juice secretion; negative regulation of phosphatase activity; negative regulation of sodium ion transport; peptidyl-serine phosphorylation; phosphorylation; positive regulation of canonical Wnt signaling pathway; positive regulation of ion transmembrane transporter activity; positive regulation of potassium ion import; positive regulation of sodium ion transmembrane transporter activity; positive regulation of systemic arterial blood pressure; positive regulation of T cell chemotaxis; protein autophosphorylation; protein phosphorylation; regulation of cellular process; regulation of sodium ion transport; signal transduction by trans-phosphorylation; T cell receptor signaling pathway