WNK3

WNK3
Identifiers
Aliases	WNK3 , PRKWNK lysine deficient protein kinase 3
External IDs	OMIM: 300358 MGI: 2652875 HomoloGene: 32493 GeneCards: WNK3
Gene location (Human)
Chr.	X chromosome (human)
End	54,358,642 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	150,103,148 bp
RNA expression pattern
	Top expressed in
	corpus epididymis; ; caput epididymis; ; secondary oocyte; ; seminal vesicula; ; internal globus pallidus; ; retinal pigment epithelium; ; ganglionic eminence; ; postcentral gyrus; ; endothelial cell; ; superior vestibular nucleus;
	Top expressed in
	hand; ; lateral hypothalamus; ; ventromedial nucleus; ; paraventricular nucleus of hypothalamus; ; dorsomedial hypothalamic nucleus; ; mammillary body; ; medial vestibular nucleus; ; ventral tegmental area; ; inferior colliculus; ; arcuate nucleus;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity ; protein kinase activity ; nucleotide binding ; kinase activity ; protein serine/threonine kinase activity ; protein binding ; chloride channel inhibitor activity ; ATP binding ; potassium channel inhibitor activity ;
Cellular component	cytoplasm ; bicellular tight junction ; adherens junction ; cytosol ;
Biological process	phosphorylation ; negative regulation of apoptotic process ; protein phosphorylation ; positive regulation of ion transmembrane transporter activity ; positive regulation of peptidyl-threonine phosphorylation ; positive regulation of sodium ion transport ; protein autophosphorylation ; positive regulation of sodium ion transmembrane transporter activity ; negative regulation of pancreatic juice secretion ; positive regulation of calcium ion transport ; intracellular signal transduction ; regulation of calcium ion import ; protein localization to plasma membrane ; positive regulation of protein localization to plasma membrane ; ion homeostasis ; negative regulation of sodium ion transport ; positive regulation of potassium ion import across plasma membrane ;
	Sources:Amigo / QuickGO
Orthologs
	65267
	279561
	ENSG00000196632
	ENSMUSG00000041245
	Q9BYP7
	Q80XP9
	NM_001002838 ; NM_020922 ; NM_001395166
	NM_001271678 ; NM_001271679
	NP_001002838 ; NP_065973
	NP_001258607 ; NP_001258608
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 20, 2024

Serine/threonine-protein kinase WNK3, also known as protein kinase lysine-deficient 3, is a protein that in humans is encoded by the WNK3 gene.^[5]

Function

WNK3 is a protein belonging to the 'with no lysine' family of serine-threonine protein kinases. These family members lack the catalytic lysine in subdomain II, and instead have a conserved lysine in subdomain I. This family member functions as a positive regulator of the transcellular Ca²⁺ transport pathway, and it plays a role in the increase of cell survival in a caspase 3 dependent pathway.^[5]

Related Research Articles

The sodium-chloride symporter (also known as Na⁺-Cl⁻ cotransporter, NCC or NCCT, or as the thiazide-sensitive Na⁺-Cl⁻ cotransporter or TSC) is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from the tubular fluid into the cells of the distal convoluted tubule of the nephron. It is a member of the SLC12 cotransporter family of electroneutral cation-coupled chloride cotransporters. In humans, it is encoded by the SLC12A3 gene (solute carrier family 12 member 3) located in 16q13.

Inositol polyphosphate 5-phosphatase OCRL-1, also known as Lowe oculocerebrorenal syndrome protein, is an enzyme encoded by the OCRL gene located on the X chromosome in humans.

<span class="mw-page-title-main">Sodium/glucose cotransporter 2</span> Protein-coding gene in the species Homo sapiens

The sodium/glucose cotransporter 2 (SGLT2) is a protein that in humans is encoded by the SLC5A2 gene.

WNK , also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine-threonine protein kinase and part of the "with no lysine/K" kinase WNK family. The predominant role of WNK1 is the regulation of cation-Cl⁻ cotransporters (CCCs) such as the sodium chloride cotransporter (NCC), basolateral Na-K-Cl symporter (NKCC1), and potassium chloride cotransporter (KCC1) located within the kidney. CCCs mediate ion homeostasis and modulate blood pressure by transporting ions in and out of the cell. WNK1 mutations as a result have been implicated in blood pressure disorders/diseases; a prime example being familial hyperkalemic hypertension (FHHt).

Electrogenic sodium bicarbonate cotransporter 1, sodium bicarbonate cotransporter is a membrane transport protein that in humans is encoded by the SLC4A4 gene.

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 cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.

Potassium-chloride transporter, member 4 is a chloride potassium symporter protein. It is encoded by the gene SLC12A4.

Cadherin-16 is a protein that in humans is encoded by the CDH16 gene.

Angiopoietin-4 is a protein that in humans is encoded by the ANGPT4 gene.

Solute carrier family 12 member 6 is a protein that in humans is encoded by the SLC12A6 gene.

STE20/SPS1-related proline-alanine-rich protein kinase is an enzyme that in humans is encoded by the STK39 gene.

Sodium/myo-inositol cotransporter is a protein that in humans is encoded by the SLC5A3 gene.

Solute carrier family 2, facilitated glucose transporter member 12 is a protein that in humans is encoded by the SLC2A12 gene.

Matrix metalloproteinase-24 is an enzyme that in humans is encoded by the MMP24 gene.

Sodium/hydrogen exchanger 8 is a protein that in humans is encoded by the SLC9A8 gene.

Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the SLC17A1 gene.

Solute carrier family 13 member 3 also called sodium-dependent dicarboxylate transporter (NaDC3) is a protein that in humans is encoded by the SLC13A3 gene.

Serine/threonine-protein kinase WNK2 is an enzyme that in humans is encoded by the WNK2 gene.

Solute carrier family 13 member 2 is a protein that is encoded in humans by the SLC13A2 gene.

Electrogenic sodium bicarbonate cotransporter 4 is a protein that in humans is encoded by the SLC4A5 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000196632 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041245 - 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.
1 2 "Entrez Gene: WNK lysine deficient protein kinase 3".

Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–37. Bibcode:2005Natur.434..325R. doi:10.1038/nature03440. PMC 2665286 . PMID 15772651.
Nagase T, Kikuno R, Nakayama M, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (4): 273–81. doi: 10.1093/dnares/7.4.271 . PMID 10997877.
Yang CL, Zhu X, Ellison DH (2007). "The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex". J. Clin. Invest. 117 (11): 3403–11. doi:10.1172/JCI32033. PMC 2045602 . PMID 17975670.
Rinehart J, Kahle KT, de Los Heros P, et al. (2005). "WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl⁻ cotransporters required for normal blood pressure homeostasis". Proc. Natl. Acad. Sci. U.S.A. 102 (46): 16777–82. Bibcode:2005PNAS..10216777R. doi: 10.1073/pnas.0508303102 . PMC 1283841 . PMID 16275913.
Ko B, Hoover RS (2009). "Molecular physiology of the thiazide-sensitive sodium-chloride cotransporter". Curr. Opin. Nephrol. Hypertens. 18 (5): 421–7. doi:10.1097/MNH.0b013e32832f2fcb. PMC 2947818 . 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". Am. J. Physiol. Renal Physiol. 295 (4): F1199-206. doi:10.1152/ajprenal.90396.2008. PMC 2576145 . PMID 18701621.
Glover M, Zuber AM, O'Shaughnessy KM (2009). "Renal and brain isoforms of WNK3 have opposite effects on NCCT expression". J. Am. Soc. Nephrol. 20 (6): 1314–22. doi:10.1681/ASN.2008050542. PMC 2689907 . PMID 19470686.
Auffray C, Behar G, Bois F, et al. (1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". Comptes Rendus de l'Académie des Sciences, Série III. 318 (2): 263–72. PMID 7757816.
Kahle KT, Ring AM, Lifton RP (2008). "Molecular physiology of the WNK kinases". Annu. Rev. Physiol. 70: 329–55. doi:10.1146/annurev.physiol.70.113006.100651. PMID 17961084.
Zhang W, Na T, Peng JB (2008). "WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway". Am. J. Physiol. Renal Physiol. 295 (5): F1472-84. doi:10.1152/ajprenal.90229.2008. PMC 2584897 . PMID 18768590.
Veríssimo F, Silva E, Morris JD, et al. (2006). "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway". Oncogene. 25 (30): 4172–82. doi:10.1038/sj.onc.1209449. PMID 16501604. S2CID 20133914.
Moniz S, Jordan P (2010). "Emerging roles for WNK kinases in cancer". Cell. Mol. Life Sci. 67 (8): 1265–76. doi:10.1007/s00018-010-0261-6. PMID 20094755. S2CID 32790065.
Talmud PJ, Drenos F, Shah S, et al. (2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". Am. J. Hum. Genet. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832 . PMID 19913121.
Qiao Y, Liu X, Harvard C, et al. (2008). "Autism-associated familial microdeletion of Xp11.22". Clin. Genet. 74 (2): 134–44. doi:10.1111/j.1399-0004.2008.01028.x. PMID 18498374. S2CID 22008997.
Wilson FH, Disse-Nicodème S, Choate KA, et al. (2001). "Human hypertension caused by mutations in WNK kinases". Science. 293 (5532): 1107–12. doi:10.1126/science.1062844. PMID 11498583. S2CID 22700809.
Heise CJ, Xu BE, Deaton SL, et al. (2010). "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members". J. Biol. Chem. 285 (33): 25161–7. doi: 10.1074/jbc.M110.103432 . PMC 2919078 . PMID 20525693.
Holden S, Cox J, Raymond FL (2004). "Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3)". Gene. 335: 109–19. doi:10.1016/j.gene.2004.03.009. PMID 15194194.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID 14702039.
Veríssimo F, Jordan P (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. S2CID 24494637.
Bailey SD, Xie C, Do R, et al. (2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168 . PMID 20628086.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000196632 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041245 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: WNK lysine deficient protein kinase 3".

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

WNK3

Contents

Function

Related Research Articles

References

Further reading