WNK4 : WNK lysine deficient protein kinase 4
Description
The WNK4 (WNK lysine deficient protein kinase 4) is a protein-coding gene located on chromosome 17.
The WNK4 gene provides instructions for making a protein that plays a role in blood pressure regulation by helping control the amount of sodium and potassium in the body. The WNK4 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions. The WNK4 protein regulates channels in the cell membrane that control the transport of sodium or potassium into and out of cells, which occurs primarily in the kidneys. Sodium channels help transport sodium into specialized kidney cells, which then transfer it into the blood. This transfer helps keep sodium in the body through a process called reabsorption. Potassium channels handle excess potassium that has been transferred from the blood into the kidney cells. The channels transport the potassium out of the cells in a process called secretion, so that it can be removed from the body in the urine. The WNK4 protein is able to promote sodium reabsorption and block potassium secretion. Depending on conditions in the cell, the WNK4 protein is also able to block (inhibit) sodium reabsorption.
Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure. The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity. Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK. Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process. Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin- dependent endocytosis. Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a kinase-independent mechanism. May also phosphorylate NEDD4L.
WNK4 is also known as PHA2B, PRKWNK4.
