Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

WNK4 (Q96J92) - Overview - Molecular Target Synopsis

Protein


WNK4, Serine/threonine-protein kinase WNK4
Enzyme Classification 2.7.11.1
UniProt Q96J92

Also Known as WNK4_HUMAN, WNK4, PRKWNK4

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. Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). Interacts with KLHL3 (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:26435498, PubMed:27727489).

4CH9
9 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE WNK4
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF THE HUMAN KLHL3 KELCH DOMAIN IN COMPLEX WITH A WNK4 PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for WNK4

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: WNK4 is active in the following subcellular-locations: cell junction, tight junction.
GO terms: WNK4 is active in the following subcellular-locations: bicellular tight junction, cytoplasm, cytosol, membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project WNK4 has gain in 2 cell-lines, loss in 2 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H226, K_562, HOP_62

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Hs 695T, NCI-H2452, NCI-H2052

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, IMR-90

(see details)

RNA Interference


WNK4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: T47D, RES259. (see details)

3D Structures


For WNK4 there are:
3 structures (6 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


WNK4 has been screened with 17 compounds (17 bioactivities). (see details)