2v3s
STRUCTURAL INSIGHTS INTO THE RECOGNITION OF SUBSTRATES AND ACTIVATORS BY THE OSR1 KINASESTRUCTURAL INSIGHTS INTO THE RECOGNITION OF SUBSTRATES AND ACTIVATORS BY THE OSR1 KINASE
Template:ABSTRACT PUBMED 17721439
DiseaseDisease
[WNK4_HUMAN] Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:614491]. PHAII is an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron.[1]
FunctionFunction
[WNK4_HUMAN] Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L.[2]
About this StructureAbout this Structure
2v3s is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP. Human hypertension caused by mutations in WNK kinases. Science. 2001 Aug 10;293(5532):1107-12. PMID:11498583 doi:10.1126/science.1062844
- ↑ Heise CJ, Xu BE, Deaton SL, Cha SK, Cheng CJ, Earnest S, Sengupta S, Juang YC, Stippec S, Xu Y, Zhao Y, Huang CL, Cobb MH. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010 Aug 13;285(33):25161-7. doi: 10.1074/jbc.M110.103432. Epub 2010, Jun 4. PMID:20525693 doi:10.1074/jbc.M110.103432