WNK1

WNK lysine deficient protein kinase 1, also known as WNK1, is an enzyme that in humans is encoded by the WNK1 is_associated_with::gene. The human gene is located on short arm of chromosome 12 (12p13.3).

WNK1 is also known as Human Accelerated Region 5. WNK1 may have played a key role in differentiating Humans from Apes.

Structure
The WNK1 protein is composed of 2382 amino acids (molecular weight 230 kDa). The protein contains a small N-terminal domain followed by the kinase domain and a long C-terminal tail. The kinase domain has some similarity to the MEKK protein kinase family.

Function
The WNK1 gene encodes a is_associated_with::cytoplasmic is_associated_with::serine-threonine kinase expressed in the distal is_associated_with::nephron.

The protein appears to be part of the is_associated_with::ERK5 is_associated_with::MAP kinase pathway upstream of MEKK2 / MEKK3 and to function as a is_associated_with::tetramer. It selectively binds to and is_associated_with::phosphorylates synaptotagmin 2 (is_associated_with::SYT2) within its calcium-binding C2 domains. It activates the serum- and glucocorticoid-inducible protein kinase is_associated_with::SGK1, leading to activation of the is_associated_with::epithelial sodium channel. It along with WNK4 stimulates clathrin-dependent endocytosis of renal outer medullar potassium 1 (ROMK1). It (and is_associated_with::WNK4) interactes with intersectin (is_associated_with::ITSN1, is_associated_with::ITSN2).

Clinical significance
WNK1 has is_associated_with::mutations associated with is_associated_with::Gordon hyperkalemia-hypertension syndrome (is_associated_with::pseudohypoaldosteronism Type II, featuring is_associated_with::hypertension) and is_associated_with::congenital sensory neuropathy (HSAN Type II, featuring loss of is_associated_with::perception to is_associated_with::pain, is_associated_with::touch, and is_associated_with::heat due to a loss of peripheral is_associated_with::sensory nerves). See also: HSN2 gene.

Comparative genomics
The gene belongs to a group of four related protein kinases (WNK1, is_associated_with::WNK2, is_associated_with::WNK3, is_associated_with::WNK4).

Homologs of this protein have been found in is_associated_with::Arabidopsis thaliana, C. elegans, is_associated_with::Chlamydomonas reinhardtii and is_associated_with::Vitis vinifera as well as in vertebrates including is_associated_with::Danio rerio and is_associated_with::Taeniopygia guttata.