WNK3 Background Information The protein kinase superfamily contains over a thousand proteins in 57 subfamilies that all share a catalytic core of 250–300 amino acids organized in two domains. WNK, for “with no lysine (K)”, kinases are serine-threonine protein kinases that contain a cysteine residue in place of a lysine residue in a family of proteins that traditionally contain a lysine following a short string of hydrophobic residues. WNK kinases contain a lysine upstream of the traditional position, within a glycine string. This lysine functions as an anchor and orients ATP through interactions with the å and ∫ phosphoryl groups. The catalytic domains of WNK2, WNK3 and WNK4 are 95% homologous to WNK1. The human WNK1 gene encodes a 2,382 amino acid protein that is primarily expressed in heart, kidney, muscle and distal nephron. The human WNK3 gene encodes a protein that is primarily expressed in brain; the human WNK4 gene encodes a 1,243 amino acid protein that is expressed in kidney. Aberrant function of WNK kinases and their associated signaling pathways are implicated in hypertension, increased renal salt reabsorption and impaired K+ and H+ excretion.
