InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: WNK4

Summary

InnateDB Protein

IDBP-51677.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

WNK4

Protein Name

WNK lysine deficient protein kinase 4

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000246914

InnateDB Gene

IDBG-51675 (WNK4)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:20525693}.

Subcellular Localization

Cell junction, tight junction {ECO:0000250}. Note=Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex (By similarity). {ECO:0000250}.

Disease Associations

Pseudohypoaldosteronism 2B (PHA2B) [MIM:614491]: An autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269PubMed:11498583}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in kidney, colon and skin. {ECO:0000269PubMed:11571656}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	19 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019869	chloride channel inhibitor activity

Biological Process

GO:0006468	protein phosphorylation
GO:0006811	ion transport
GO:0006821	chloride transport
GO:0008104	protein localization
GO:0035556	intracellular signal transduction
GO:0050794	regulation of cellular process
GO:0050801	ion homeostasis
GO:0070294	renal sodium ion absorption
GO:0072156	distal tubule morphogenesis
GO:0090188	negative regulation of pancreatic juice secretion

Cellular Component

GO:0005737	cytoplasm
GO:0005923	tight junction

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR024678 Serine/threonine-protein kinase OSR1/WNK, CCT domain

PFAM

PF00069
PF07714
PF12202

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt