ID:WNK4_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase WNK4; EC=2.7.11.1; AltName: Full=Protein kinase lysine-deficient 4; AltName: Full=Protein kinase with no lysine 4; FUNCTION: 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activation requires autophosphorylation of Ser- 335. Phosphorylation of Ser-331 also promotes increased activity (By similarity). SUBUNIT: Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). SUBCELLULAR LOCATION: Cell junction, tight junction (By similarity). Note=Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex (By similarity). TISSUE SPECIFICITY: Expressed in kidney, colon and skin. PTM: Phosphorylated by WNK1 and WNK3 (By similarity). DISEASE: Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:614491]. PHAII is an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. SIMILARITY: Contains 1 protein kinase domain. CAUTION: Cys-203 is present instead of the conserved Lys which is expected to be an active site residue. Lys-186 appears to fulfill the required catalytic function. SEQUENCE CAUTION: Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAC48387.1; Type=Frameshift; Positions=4; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK4";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96J92
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
