Recombinant human WNK1 protein

Specifications

Form

Liquid

Additional notes

Purity was determined to be >95% by densitometry. Affinity purified.

General info

Function

Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed : 15883153, PubMed : 17190791, PubMed : 31656913, PubMed : 34289367, PubMed : 36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed : 36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed : 15883153, PubMed : 16263722, PubMed : 17190791, PubMed : 19739668, PubMed : 21321328, PubMed : 22989884, PubMed : 25477473, PubMed : 34289367, PubMed : 36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed : 16263722, PubMed : 21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed : 19665974, PubMed : 21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK : activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed : 25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed : 29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed : 29196535). Acts as a negative regulator of autophagy (PubMed : 27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed : 21220314). May also play a role in actin cytoskeletal reorganization (PubMed : 10660600). Also acts as a scaffold protein independently of its protein kinase activity : negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner : probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed : 36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity : associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed : 33964204).. Isoform 3. Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed : 14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity).

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.

Post-translational modifications

Autophosphorylated at Ser-378 and Ser-382, promoting its activity (PubMed:15883153, PubMed:16263722, PubMed:16832045, PubMed:17190791, PubMed:31656913, PubMed:34289367). Autophosphorylation at Ser-382 is inhibited by intracellular calcium (By similarity). Phosphorylation at Thr-60 increases ability to activate SGK1 (By similarity).. Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation (PubMed:23387299, PubMed:23576762). Also ubiquitinated by the BCR(KLHL2) complex (PubMed:23838290).. May be O-glycosylated.