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

WNK3 (Q9BYP7) - Overview - Molecular Target Synopsis

Protein


WNK3, Serine/threonine-protein kinase WNK3
Enzyme Classification 2.7.11.1
UniProt Q9BYP7

Also Known as WNK3_HUMAN, WNK3, KIAA1566, PRKWNK3

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 (PubMed:16275913, PubMed:16275911, PubMed:16357011). Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner., Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686, isoform 1 inhibits the activity of SLC12A3. Interacts with WNK1 and WNK4.

5O23
CRYSTAL STRUCTURE OF WNK3 KINASE DOMAIN IN A MONOPHOSPHORYLATED APO STATE
RCSB/PDB
Inspect Structure
See all 3D Structures for WNK3

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: WNK3 is active in the following subcellular-locations: cytoplasm.
GO terms: WNK3 is active in the following subcellular-locations: adherens junction, bicellular tight junction, cytoplasm, cytosol.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project WNK3 has gain in 2 cell-lines, loss in 57 cell-lines and no signal in 946 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_8, SK_MEL_2, OVCAR_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NTERA-2, A-375, NCI-H209

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, NHLF, HSMM

(see details)

RNA Interference


WNK3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: VP229, TE6. (see details)

3D Structures


For WNK3 there are:
7 structures (13 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


WNK3 has been screened with 178 compounds (343 bioactivities), 2 compounds have bioactivities that show binding affinity of <= 500nM (2 bioactivities). (see details)