4ch9: Difference between revisions

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'''Unreleased structure'''
{{STRUCTURE_4ch9|  PDB=4ch9  |  SCENE=  }}
===Crystal structure of the human KLHL3 Kelch domain in complex with a WNK4 peptide===


The entry 4ch9 is ON HOLD until Paper Publication
==Disease==
[[http://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN]] Pseudohypoaldosteronism type 2D. The disease is caused by mutations affecting the gene represented in this entry. [[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>  


Authors: Sorrell, F.J., Schumacher, F.R., Kurz, T., Alessi, D.R., Newman, J., Goubin, S., Chalk, R., Kopec, J., Tallant, C., Williams, E., Krojer, T., Von Delft, F., Arrowsmith, C.H., Edwards, A.M., Bountra, C., Bullock, A.
==Function==
[[http://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN]] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation.<ref>PMID:14528312</ref> <ref>PMID:23387299</ref> <ref>PMID:23453970</ref> <ref>PMID:23665031</ref> <ref>PMID:23576762</ref> <ref>PMID:22406640</ref>  [[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> 


Description: Crystal structure of the human KLHL3 Kelch domain in complex with a WNK4 peptide
==About this Structure==
[[4ch9]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH9 OCA].
 
==Reference==
<references group="xtra"/><references/>
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Alessi, D R.]]
[[Category: Arrowsmith, C H.]]
[[Category: Bountra, C.]]
[[Category: Bullock, A.]]
[[Category: Chalk, R.]]
[[Category: Delft, F Von.]]
[[Category: Edwards, A M.]]
[[Category: Goubin, S.]]
[[Category: Kopec, J.]]
[[Category: Krojer, T.]]
[[Category: Kurz, T.]]
[[Category: Newman, J.]]
[[Category: Schumacher, F R.]]
[[Category: Sorrell, F J.]]
[[Category: Tallant, C.]]
[[Category: Williams, E.]]
[[Category: Adaptor protein]]
[[Category: Kelch repeat]]
[[Category: Klhl3]]
[[Category: Protein-binding]]
[[Category: Signaling protein-transferase complex]]
[[Category: Ubiquitin]]
[[Category: Wnk signalling pathway]]
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