2v3s: Difference between revisions
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{{STRUCTURE_2v3s| PDB=2v3s | SCENE= }} | {{STRUCTURE_2v3s| PDB=2v3s | SCENE= }} | ||
===STRUCTURAL INSIGHTS INTO THE RECOGNITION OF SUBSTRATES AND ACTIVATORS BY THE OSR1 KINASE=== | |||
{{ABSTRACT_PUBMED_17721439}} | |||
== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/WNK4_HUMAN WNK4_HUMAN]] Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:[http://omim.org/entry/614491 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.<ref>PMID:11498583</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/WNK4_HUMAN 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.<ref>PMID:20525693</ref> | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:017721439</ref><references group="xtra"/> | <ref group="xtra">PMID:017721439</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
