WNK4 - Serine/threonine-protein kinase WNK4 - human protein (Function)
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WNK4 »  Serine/threonine-protein kinase WNK4   [ EC ]
Protein also known as:  Protein kinase lysine-deficient 4.
Gene name:  WNK4
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • ISSOrtholog Curator
Chloride channel inhibitor activitydefinition[GO:0019869]  
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
  • IPIUniProtKB
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
  • ISSOrtholog Curator
GO biological process 
Chloride transportdefinition[GO:0006821] silver  
  • IEAOrtholog Compara
Distal tubule morphogenesisdefinition[GO:0072156]  
  • IMPUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
  • ISSOrtholog Curator
Ion homeostasisdefinition[GO:0050801]  
  • IMPUniProtKB
Ion transportdefinition[GO:0006811]  
  • ISSOrtholog Curator
Negative regulation of pancreatic juice secretiondefinition[GO:0090188] silver  
  • IEAOrtholog Compara
Protein localizationdefinition[GO:0008104] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
  • ISSOrtholog Curator
Regulation of cellular processdefinition[GO:0050794]  
  • ISSOrtholog Curator
Renal sodium ion absorptiondefinition[GO:0070294]  
  • IMPUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).  
  • CuratedUniProtKB
According to Reactome, this protein belongs to the following pathway:
Stimuli-sensing channels  REACT_160189  
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.  
  • CuratedUniProtKB


Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: WNK4
GenomeRNAi: 65266
PRO: PR:Q96J92