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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
a) pseudohypoaldosteronism type 2
b) hereditary sensory & autonomic neuropathy type 2A
Note:
- 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
Related
pseudohypoaldosteronism type 2 (Gordon syndrome)
General
serine/threonine protein kinase WNK (protein kinase with no lysine, protein kinase lysine-deficient)
Properties
SIZE: entity length = 2382 aa
MW = 251 kD
COMPARTMENT: cytoplasm
STATE: active state
MOTIF: Ser phosphorylation site {S19}
Ser phosphorylation site {S167}
Ser phosphorylation site {S174}
kinase domain
SITE: 221-479
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 233-233
ATP-binding site
NAME: ATP-binding site
SITE: 227-235
aspartate residue {D349}
Ser phosphorylation site {S378}
Ser phosphorylation site {S382}
Ser phosphorylation site {S1261}
Ser phosphorylation site {S1297}
Ser phosphorylation site {S1300}
Ser phosphorylation site {S1978}
Ser phosphorylation site {S2002}
Ser phosphorylation site {S2011}
Ser phosphorylation site {S2012}
Ser phosphorylation site {S2027}
Ser phosphorylation site {S2029}
Ser phosphorylation site {S2032}
Ser phosphorylation site {S2038}
Ser phosphorylation site {S2121}
Ser phosphorylation site {S2372}
Database Correlations
OMIM correlations
MORBIDMAP 605232
UniProt Q9H4A3
PFAM correlations
Entrez Gene 65125
Kegg hsa:65125
ENZYME 2.7.11.1
References
- UniProt :accession Q9H4A3
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/WNK1