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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.
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| Protein type: EC 2.7.11.1; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Wnk family |
| Chromosomal Location of mouse Ortholog: 11|11 D |
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Cellular Component:
bicellular tight junction; cell body; cell junction; cytoplasm; cytosol; membrane; protein-containing complex
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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
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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
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Reference #:
Q80UE6
(UniProtKB)
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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
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Gene Symbols: Wnk4
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Molecular weight:
132,410 Da
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Basal Isoelectric point:
5.4
Predict pI for various phosphorylation states
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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