Background: | 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 (By similarity). |
Synonyms: | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4), WNK4, PRKWNK4 |
UniProt Protein Function: | 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.Protein type: Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; EC 2.7.11.1; Other group; Wnk familyChromosomal Location of Human Ortholog: 17q21-q22Cellular Component: tight junction; cytoplasmMolecular Function: protein serine/threonine kinase activity; protein binding; chloride channel inhibitor activity; ATP bindingBiological Process: protein localization; ion homeostasis; regulation of cellular process; ion transport; chloride transport; protein amino acid phosphorylationDisease: Pseudohypoaldosteronism, Type Iib |
UniProt Protein Details: | |
NCBI Summary: | |
UniProt Code: | Q96J92 |
NCBI GenInfo Identifier: | 34365793 |
NCBI Gene ID: | 65266 |
NCBI Accession: | NP_115763.2 |
UniProt Secondary Accession: | Q96J92,Q8N8X3, Q8N8Z2, Q96DT8, Q9BYS5, B0LPI0 |
UniProt Related Accession: | Q96J92 |
Molecular Weight: | 134,739 Da |
NCBI Full Name: | serine/threonine-protein kinase WNK4 |
NCBI Synonym Full Names: | WNK lysine deficient protein kinase 4 |
NCBI Official Symbol: | WNK4Â Â |
NCBI Official Synonym Symbols: | PHA2B; PRKWNK4Â Â |
NCBI Protein Information: | serine/threonine-protein kinase WNK4; protein kinase with no lysine 4; protein kinase lysine-deficient 4 |
UniProt Protein Name: | Serine/threonine-protein kinase WNK4 |
UniProt Synonym Protein Names: | Protein kinase lysine-deficient 4; Protein kinase with no lysine 4 |
Protein Family: | Serine/threonine-protein kinase |
UniProt Gene Name: | WNK4Â Â |
UniProt Entry Name: | WNK4_HUMAN |