positive regulation of ion transmembrane transporter activity
positive regulation of potassium ion import across plasma membrane
positive regulation of sodium ion transmembrane transporter activity
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
65266
69847
Ensembl
ENSG00000126562
ENSMUSG00000035112
UniProt
Q96J92
Q80UE6
RefSeq (mRNA)
NM_032387 NM_001321299
NM_175638
RefSeq (protein)
NP_001308228 NP_115763
NP_783569
Location (UCSC)
Chr 17: 42.78 – 42.8 Mb
Chr 11: 101.15 – 101.17 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene.[5] Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.
WNK4 is a member of a serine/threonine kinase family that comprises four members. The family is so named because unlike other serine/threonine kinases, WNKs are characterized by the lack of the lysine in the subdomain II of the catalytic domain.[6] Instead, a lysine in the β2 strand of subdomain I of the catalytic domain is responsible for the kinase activity.[6]
The WNK4 gene is located on chromosome 17q21-q22. It produces a 1,243-amino acid protein encoded by a 3,732-nucleotide open reading frame within a 4 kb cDNA transcript.[7] WNK4 protein is highly expressed in the distal convoluted tubule (DCT) and the cortical collecting duct (CDD) of the kidney.[7] WNK4 is also present in the brain, lungs, liver, heart, and colon of various mammalian species.[8][9]
Gene mutations in WNK4 has been found in patients with pseudohypoaldosteronism type II (PHAII),[7] also known as familial hyperkalemic hypertension (FHHt)[10] or Gordon syndrome.[11] PHAII is an autosomal dominant hereditary disease characterized by hyperkalemia, hypertension, and metabolic acidosis. WNK4 plays a critical role in the regulation of various transporters and channels in the kidney. PHAII-causing mutations in WNK4 result in the dysregulation of renal sodium and potassium transporters and channels, leading to defects in sodium and potassium retention by the kidney, and in turn, elevated blood pressure and potassium level (hyperkalemia).
^ abcGRCh38: Ensembl release 89: ENSG00000126562 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000035112 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Entrez Gene: WNK4 WNK lysine deficient protein kinase 4".
^ abXu B, English JM, Wilsbacher JL, Stippec S, Goldsmith EJ, Cobb MH (June 2000). "WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II". The Journal of Biological Chemistry. 275 (22): 16795–801. doi:10.1074/jbc.275.22.16795. PMID 10828064.
^ abcWilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, et al. (August 2001). "Human hypertension caused by mutations in WNK kinases". Science. 293 (5532): 1107–12. doi:10.1126/science.1062844. PMID 11498583. S2CID 22700809.
^Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B, et al. (February 2004). "WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia". Proceedings of the National Academy of Sciences of the United States of America. 101 (7): 2064–9. doi:10.1073/pnas.0308434100. PMC 357052. PMID 14769928.
^Veríssimo F, Jordan P (September 2001). "WNK kinases, a novel protein kinase subfamily in multi-cellular organisms". Oncogene. 20 (39): 5562–9. doi:10.1038/sj.onc.1204726. PMID 11571656.
^Arnold JE, Healy JK (September 1969). "Hyperkalemia, hypertension and systemic acidosis without renal failure associated with a tubular defect in potassium excretion". The American Journal of Medicine. 47 (3): 461–72. doi:10.1016/0002-9343(69)90230-7. PMID 5808659.
^Gordon RD, Geddes RA, Pawsey CG, O'Halloran MW (November 1970). "Hypertension and severe hyperkalaemia associated with suppression of renin and aldosterone and completely reversed by dietary sodium restriction". Australasian Annals of Medicine. 19 (4): 287–94. doi:10.1111/imj.1970.19.4.287. PMID 5490655.
Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations...
sodium transporters in the kidney. PHA2 is associated with mutations in the WNK4, WNK1, KLHL3 and CUL3 genes. These genes regulate the Sodium-chloride symporter...
called WNK kinases. There are 4 different WNK kinases, WNK1, WNK2, WNK3, and WNK4. It also participates in calcium regulation by reabsorbing Ca2+ in response...
catalytic domain. Furthermore, WNK1 and WNK4 may interact to form heterodimers that inhibit WNK1 function. WNK4 release from the heterodimer allows WNK1...
one of the STADAN stations A group of kinases called WNK WNK1 WNK2 WNK3 WNK4 This disambiguation page lists articles associated with the title WNK. If...
Murthy M, Cope G, O'Shaughnessy KM (October 2008). "The acidic motif of WNK4 is crucial for its interaction with the K channel ROMK". Biochemical and...
regulating the proteasomal degradation of With-no-lysine [K] kinases WNK1 and WNK4. It was shown that mutations in CUL3 gene lead to WNKs accumulation. The...
PMID 19636250. San-Cristobal P, Ponce-Coria J, Vázquez N, et al. (2008). "WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl− cotransporter"...
Zhang W, Wu G, Liu C, Peng JB (Jan 2011). "Concerted actions of NHERF2 and WNK4 in regulating TRPV5". Biochemical and Biophysical Research Communications...
has been reported recently. AATK is thought to indirectly inhibit the SPAK/WNK4 activation of the Na-K-Cl cotransporter. GRCh38: Ensembl release 89: ENSG00000181409...
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