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serine/threonine protein kinase WNK4;; protein kinase lysine-deficient 4; protein kinase with no lysine 4 (WNK4, PRKWNK4)

Function: - serine/threonine protein kinase - role in regulation of electrolyte homeostasis, cell signaling, cell survival & cell proliferation - activator of Na+-coupled chloride cotransporters - inhibitor of K+-coupled chloride cotransporters - activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 & TRPV6 - regulates activity of 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 KCNJ1 from the cell surface by clathrin-dependent endocytosis - WNK4 appears to act as a molecular switch that can vary the balance between Na+ reabsorption & K+ secretion - phosphorylates NEDD4L - activation requires autophosphorylation of Ser-335 - phosphorylation of Ser-331 increases activity - phosphorylated by WNK1 & WNK3 (putative) - interacts with the C-terminal region of KCNJ1 - interacts with WNK1 & WNK3 (putative) Cofactor: Mg+2 (putative) Structure: - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily - contains 1 protein kinase domain Compartment: - cell junction, tight junction - present exclusively in intercellular junctions in the distal convoluted tubule & in both the cytoplasm & intercellular junctions in the cortical collecting duct - WNK4 is part of the tight junction complex (putative) Alternative splicing: named isoforms=3 Expression: expressed in kidney, colon & skin Pathology: - defects in WNK4 are a cause of pseudohypoaldosteronism type 2

Related

pseudohypoaldosteronism type 2 (Gordon syndrome)

General

serine/threonine protein kinase WNK (protein kinase with no lysine, protein kinase lysine-deficient)

Properties

SIZE: entity length = 1243 aa MW = 135 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 174-432 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 186-186 ATP-binding site NAME: ATP-binding site SITE: 180-188 aspartate residue {D302} Ser phosphorylation site {S331} Ser phosphorylation site {S335}

Database Correlations

OMIM correlations UniProt Q96J92 PFAM correlations Entrez Gene 65266 Kegg hsa:65266 ENZYME 2.7.11.1

References

  1. UniProt :accession Q96J92
  2. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/WNK4