Tchem WNK1 Serine/threonine-protein kinase WNK1

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 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 (By similarity). 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. This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]

Uniprot Accession IDs

• Q9H4A3
• A1L4B0
• C5HTZ5
• C5HTZ6
• C5HTZ7
• H6WZW3
• O15052
• P54963
• Q4VBX9
• Q6IFS5
• Q86WL5
• Q8N673
• Q96CZ6
• Q9P1S9

Gene Name

• WNK1

Ensembl ID

• ENST00000315939
• ENSP00000313059
• ENSG00000060237
• ENST00000340908
• ENSP00000341292
• ENST00000530271
• ENSP00000433548
• ENST00000537687
• ENSP00000444465

Symbol

• HSN2
• KDP
• KIAA0344
• PRKWNK1
• KDP
• PSK
• p65
• HSN2
• HSAN2
• PRKWNK1
• PPP1R167

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
transcription factor binding site profile	0.96
transcription factor perturbation	0.96
kinase	0.87
ligand (protein) perturbation	0.83

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Wnk1

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Wnk Family / Serine/threonine-protein Kinase Wnk1

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: 374.4   (req: < 5)

Gene RIFs: 104   (req: <= 3)

Antibodies: 548   (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: 374.4   (req: >= 5)

Gene RIFs: 104   (req: > 3)

Antibodies: 548   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

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

Active Ligands: 3

Tclin

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

Active Drug: 0