serine/threonine protein kinase WNK1; erythrocyte 65 kD protein; p65; kinase deficient protein; protein kinase lysine-deficient 1; protein kinase with no lysine 1; hWNK1 (WNK1, HSN2, KDP, KIAA0344, PRKWNK1)

Function

• serine/threonine protein kinase
• role in regulation of electrolyte homeostasis, cell signaling, cell survival, & cell proliferation
• activator of Na+-coupled chloride cotransporters
• inhibitor of K+-coupled chloride cotransporters
• activates SCNN1A, SCNN1B, SCNN1D & SGK1
• controls Na+ & chloride transport by inhibiting activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 & the autoinhibitory domain of WNK1
• WNK4 regulates activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation
• WNK1 may also play a role in actin cytoskeletal reorganization phosphorylates NEDD4L (putative)
• activity regulated by hypertonicity
• activation requires autophosphorylation of Ser-382
• phosphorylation of Ser-378 also promotes increased activity (putative)
• phosphorylated upon DNA damage, probably by ATM or ATR
• interacts with SYT2 (putative)
• interacts with WNK3 & WNK4 (putative)

Cofactor: Mg+2

Structure

• O-glycosylated
• belongs to the protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily
• contains 1 protein kinase domain

Compartment

cytoplasm

Alternative splicing

• named isoforms=5
• alternative promoter usage

Expression

• widely expressed
• highest levels in testis, heart, kidney & skeletal muscle
• isoform 3 is kidney-specific

Pathology

• defects in WNK1 are a cause of
  • pseudohypoaldosteronism type 2
  • hereditary sensory & autonomic neuropathy type 2A

Notes

• HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron.
• it is a nervous system-specific exon of WNK1 included in isoform 4 & isoform 5
• uncertain whether Met-1 or Met-214 is the initiator in isoform 4 & isoform 5

More general terms

• serine/threonine protein kinase WNK

Additional terms

• pseudohypoaldosteronism type 2 (Gordon syndrome)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=65125
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:65125
• OMIM: https://mirror.omim.org/entry/145260
• OMIM: https://mirror.omim.org/entry/201300
• OMIM: https://mirror.omim.org/entry/605232
• UniProt: http://www.uniprot.org/uniprot/Q9H4A3.html