WNK1

From Wikipedia, the free encyclopedia
Jump to: navigation, search
WNK1
Protein WNK1 PDB 1t4h.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases WNK1, HSAN2, HSN2, KDP, PPP1R167, PRKPSK, p65, WNK lysine deficient protein kinase 1
External IDs MGI: 2442092 HomoloGene: 14253 GeneCards: 65125
RNA expression pattern
PBB GE WNK1 211992 at tn.png

PBB GE WNK1 211993 at tn.png

PBB GE WNK1 211994 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001184985
NM_014823
NM_018979
NM_213655

RefSeq (protein)

NP_001171914.1
NP_055638.2
NP_061852.3
NP_998820.3

NP_001171949.1
NP_001171950.1
NP_001186012.1
NP_001186013.1
NP_941992.2

Location (UCSC) Chr 12: 0.75 – 0.91 Mb Chr 6: 119.92 – 120.04 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

WNK lysine deficient protein kinase 1, also known as WNK1, is an enzyme that in humans is encoded by the WNK1 gene.[1] 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[edit]

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[edit]

The WNK1 gene encodes a cytoplasmic serine-threonine kinase expressed in the distal nephron.[1]

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

Clinical significance[edit]

WNK1 has mutations associated with Gordon hyperkalemia-hypertension syndrome (pseudohypoaldosteronism Type II, featuring hypertension) and congenital sensory neuropathy (HSAN Type II, featuring loss of perception to pain, touch, and heat due to a loss of peripheral sensory nerves).[2] See also: HSN2 gene.

Comparative genomics[edit]

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

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

References[edit]

  1. ^ a b "Entrez Gene: WNK1 WNK lysine deficient protein kinase 1". 
  2. ^ Shekarabi M, Girard N, Rivière JB, et al. (July 2008). "Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II". J Clin Invest. 118 (7): 2496–2505. doi:10.1172/JCI34088. PMC 2398735. PMID 18521183. Retrieved 2008-11-04. 

Further reading[edit]

External links[edit]