4chb
Crystal structure of the human KLHL2 Kelch domain in complex with a WNK4 peptideCrystal structure of the human KLHL2 Kelch domain in complex with a WNK4 peptide
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
[KLHL2_HUMAN] May play a role in organizing the actin cytoskeleton of the brain cells. [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
4chb is a 4 chain structure. 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
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OCA- Non-specific serine/threonine protein kinase
- Alessi, D R.
- Arrowsmith, C H.
- Bountra, C.
- Bullock, A.
- Canning, P.
- Cooper, C D.O.
- Delft, F Von.
- Edwards, A M.
- Kopec, J.
- Krojer, T.
- Kurz, T.
- Newman, J.
- Schumacher, F R.
- Sorrell, F J.
- Williams, E.
- Adaptor protein
- Kelch repeat
- Klhl3
- Protein-binding
- Signaling protein-transferase complex
- Ubiquitin
- Wnk signalling pathway