Tbio WNK4 Serine/threonine-protein kinase WNK4

Protein Summary

Description

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. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity). This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]

Uniprot Accession IDs

• Q96J92
• B0LPI0
• Q8N8X3
• Q8N8Z2
• Q96DT8
• Q9BYS5

Gene Name

• WNK4

Ensembl ID

• ENST00000246914
• ENSP00000246914
• ENSG00000126562

Symbol

• PRKWNK4
• PHA2B
• PRKWNK4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.97
tissue sample	0.69
transcription factor	0.66
kinase	0.6
kinase perturbation	0.6

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Wnk4

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Wnk Family / Serine/threonine-protein Kinase Wnk4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 161.71   (req: < 5)

Gene RIFs: 59   (req: <= 3)

Antibodies: 219   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 161.71   (req: >= 5)

Gene RIFs: 59   (req: > 3)

Antibodies: 219   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0