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

WNK1 (Q9H4A3) - Overview - Molecular Target Synopsis

Protein


WNK1, Serine/threonine-protein kinase WNK1
Enzyme Classification 2.7.11.1
UniProt Q9H4A3

Also Known as WNK1_HUMAN, WNK1, HSN2, KDP, KIAA0344, PRKWNK1

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 and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition., Isoform 3: Dominant-negative regulator of the longer isoform 1. Does not have kinase activity, does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Downregulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity. In kidney, may play an important role regulating sodium and potassium balance. Interacts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity). Interacts with KLHL3 (PubMed:23387299, PubMed:23576762). Isoform 3: Interacts with isoform 1.

6FBK
17 RESIDUE FRAGMENT OF
SERINE/THREONINE-PROTEIN KINASE WNK1
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF THE HUMAN WNK2 CCT-LIKE 1 DOMAIN IN COMPLEX WITH A WNK1 RFXV PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for WNK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: WNK1 is active in the following subcellular-locations: cytoplasm.
GO terms: WNK1 is active in the following subcellular-locations: cytoplasm, cytosol, membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project WNK1 has gain in 8 cell-lines, loss in 2 cell-lines and no signal in 994 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HOP_62, SF_268, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: KP4, SK-N-FI, HOP-62

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: HSMM, HeLa-S3, NHLF

(see details)

RNA Interference


WNK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H358, CASKI. (see details)

3D Structures


For WNK1 there are:
8 structures (13 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


WNK1 has been screened with 35 compounds (37 bioactivities). (see details)