Human Gene WNK4 (ENST00000246914.10) from GENCODE V44
Description: Homo sapiens WNK lysine deficient protein kinase 4 (WNK4), transcript variant 1, mRNA. (from RefSeq NM_032387) RefSeq Summary (NM_032387): This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]. Gencode Transcript: ENST00000246914.10 Gencode Gene: ENSG00000126562.17 Transcript (Including UTRs) Position: hg38 chr17:42,780,610-42,797,066 Size: 16,457 Total Exon Count: 19 Strand: + Coding Region Position: hg38 chr17:42,780,699-42,796,688 Size: 15,990 Coding Exon Count: 19
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.