WNK1

WNK1 is 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.

WNK Lysine Deficient Protein Kinase 1

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. Down-regulates 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.

Biological Process cation homeostasis Source:UniProtKB
Biological Process cellular chloride ion homeostasis Source:Ensembl
Biological Process cellular response to chemokine Source:BHF-UCL1 Publication
Biological Process chemokine (C-C motif) ligand 21 signaling pathway Source:BHF-UCLBy Similarity
Biological Process intracellular signal transduction Source:UniProtKB1 Publication
Biological Process ion homeostasis Source:GO_Central1 Publication
Biological Process ion transport Source:UniProtKB
Biological Process lymphocyte migration into lymph node Source:BHF-UCLBy Similarity
Biological Process negative regulation of cell-cell adhesion mediated by integrin Source:BHF-UCL1 Publication
Biological Process negative regulation of GTPase activity Source:BHF-UCL1 Publication
Biological Process negative regulation of heterotypic cell-cell adhesion Source:BHF-UCL1 Publication
Biological Process negative regulation of leukocyte cell-cell adhesion Source:BHF-UCL1 Publication
Biological Process negative regulation of pancreatic juice secretion Source:Ensembl
Biological Process negative regulation of sodium ion transport Source:UniProtKB1 Publication
Biological Process neuron development Source:UniProtKB1 Publication
Biological Process peptidyl-serine phosphorylation Source:BHF-UCLBy Similarity
Biological Process peptidyl-threonine phosphorylation Source:ARUK-UCL1 Publication
Biological Process positive regulation of canonical Wnt signaling pathway Source:FlyBase1 Publication
Biological Process positive regulation of potassium ion import across plasma membrane Source:GO_Central1 Publication
Biological Process positive regulation of sodium ion transmembrane transporter activity Source:GO_Central1 Publication
Biological Process positive regulation of systemic arterial blood pressure Source:Ensembl
Biological Process positive regulation of T cell chemotaxis Source:BHF-UCL1 Publication
Biological Process potassium ion homeostasis Source:Ensembl
Biological Process protein phosphorylation Source:UniProtKB1 Publication
Biological Process regulation of cation transmembrane transport Source:ARUK-UCL1 Publication
Biological Process regulation of sodium ion transport Source:UniProtKB
Biological Process signal transduction Source:ParkinsonsUK-UCL1 Publication
Biological Process sodium ion transmembrane transport Source:Ensembl
Biological Process T cell receptor signaling pathway Source:BHF-UCLBy Similarity

Cytoplasm

Pseudohypoaldosteronism 2C (PHA2C):
An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics.
Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A):
A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves.

Autophosphorylation at Ser-382 is inhibited by intracellular calcium.
May be O-glycosylated.
Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a BCR(KLHL2) complex, leading to proteasomal degradation.