serine/threonine protein kinase WNK2; antigen NY-CO-43; protein kinase lysine-deficient 2; protein kinase with no lysine 2; serologically defined colon cancer antigen 43 (WNK2, KIAA1760, PRKWNK2, SDCCAG43, P/OKcl13)

Function: - serine/threonine protein kinase - role in regulation of electrolyte homeostasis, cell signaling, survival, & proliferation - activator of Na⁺-coupled chloride cotransporters - inhibitor of K⁺-coupled chloride cotransporters - activates SLC12A2, SCNN1A, SCNN1B, SCNN1D & SGK1 - inhibits SLC12A5 - negatively regulates EGF-induced activation of the ERK/MAPK-pathway & downstream cell cycle progression - affects MAPK3/MAPK1 activity by modulating activity of MAP2K1 - modulation depends on phosphorylation of MAP2K1 by PAK1 - WNK2 acts by interfering with activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA & RAC1, which display reciprocal activity - activation requires autophosphorylation of Ser-356 - phosphorylation of Ser-352 also promotes increased activity - autophosphorylated - forms a complex with the phosphorylated form of STK39 Cofactor: Mg⁺² (putative) Structure: - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily - contains 1 protein kinase domain Compartment: cytoplasm. cell membrane Alternative splicing: named isoforms=4 Expression: - expressed in various cancer cell lines (at protein level) - predominantly expressed in heart, brain, skeletal muscle & colon Notes: - Cys-224 is present instead of the conserved Lys within the kinase domain - Lys-207 appears to fulfill the required catalytic function

Properties

SIZE: entity length = 2297 aa MW = 243 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: Ser phosphorylation site {S45} Ser phosphorylation site {S49} kinase domain SITE: 195-453 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 207-207 ATP-binding site NAME: ATP-binding site SITE: 201-209 aspartate residue {D323} Ser phosphorylation site {S352} Ser phosphorylation site {S356} Ser phosphorylation site {S560} Ser phosphorylation site {S1150} Ser phosphorylation site {S1262} Ser phosphorylation site {S1588} Ser phosphorylation site {S1685} Ser phosphorylation site {S1736} Ser phosphorylation site {S1817} Ser phosphorylation site {S1818} Ser phosphorylation site {S1862} Ser phosphorylation site {S1889} Ser phosphorylation site {S2067}

Database Correlations

OMIM 606249 UniProt Q9Y3S1 PFAM correlations Entrez Gene 65268 Kegg hsa:65268 ENZYME 2.7.11.1

References

UniProt :accession Q9Y3S1