WNK3 Q9BYP7

丝氨酸/苏氨酸蛋白激酶WNK3 (EC 2.7.11.1) (赖氨酸缺陷蛋白激酶3) (无赖氨酸蛋白激酶3)

功能描述

WNK3-SPAK/OSR1激酶级联反应的丝氨酸/苏氨酸蛋白激酶组分，该级联反应在电解质稳态调节及响应高渗应激的调节性体积增加中发挥重要作用 (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922)。WNK3通过作为分子拥挤传感器介导响应高渗应激的调节性体积增加，该传感器感知细胞收缩并通过经历液-液相分离介导无膜区室的形成 (PubMed:36318922)。该无膜区室将WNK3与其底物OXSR1/OSR1和STK39/SPAK浓缩在一起，促进依赖WNK3的下游激酶OXSR1/OSR1和STK39/SPAK的磷酸化及激活 (PubMed:22989884)。激活后，OXSR1/OSR1和STK39/SPAK催化离子共转运体SLC12A1/NKCC2、SLC12A2/NKCC1、SLC12A3/NCC、SLC12A4/KCC1、SLC12A5/KCC2或SLC12A6/KCC3的磷酸化，调节其活性 (PubMed:16275911, PubMed:16275913)。Na-K-Cl共转运体SLC12A2/NKCC1和SLC12A2/NKCC1的磷酸化促进其激活和离子内流；同时，K-Cl共转运体SLC12A4/KCC1、SLC12A5/KCC2和SLC12A6/KCC3的磷酸化抑制其活性，阻断离子外流 (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606)。磷酸化WNK4，可能调节SLC12A3/NCC的活性 (PubMed:17975670)。也可能磷酸化NEDD4L (PubMed:20525693)。亦作为支架蛋白独立于其蛋白激酶活性发挥作用：负向调节各种转运体和通道（如KCNJ1和SLC26A9）的细胞膜定位 (PubMed:16357011, PubMed:17673510)。通过激酶依赖性途径增强TRPV5和TRPV6的膜表达水平，从而增加由其介导的Ca(2+)内流 (PubMed:18768590)。 {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}。

组织特异性

Expressed in brain, lung, kidney, liver and pancreas, and in fetal tissues including placenta, fetal brain, lung and kidney. Very low levels of expression were also detected in fetal heart, thymus, liver and spleen. Isoform 1 is brain-specific. Isoform 3 is kidney-specific.

亚细胞定位

Cytoplasm