WNK3

Identifiers

WNK3, PRKWNK lysine deficient protein kinase 3

External IDs

MGI: 2652875 HomoloGene: 32493 GeneCards: WNK3

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
Cellular component	• cytoplasm • bicellular tight junction • adherens junction • cytosol
Biological process	• phosphorylation • positive regulation of rubidium ion transport • negative regulation of apoptotic process • positive regulation of rubidium ion transmembrane transporter activity • positive regulation of establishment of protein localization to plasma membrane • protein phosphorylation • regulation of ion homeostasis • 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 targeting to plasma membrane
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


65267


279561

Ensembl


ENSG00000196632


ENSMUSG00000041245

UniProt


Q9BYP7


Q80XP9

RefSeq (mRNA)


NM_001002838 NM_020922


NM_001271678 NM_001271679

RefSeq (protein)


NP_001002838.1 NP_065973.2


NP_001258607.1 NP_001258608.1

Location (UCSC)

Chr X: 54.19 – 54.36 Mb

Chr X: 151.2 – 151.32 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

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.^[3]

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.^[3]

References

Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome". Nature. 434 (7031): 325–37. 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. 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]". C. R. Acad. Sci. III, Sci. Vie. 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.
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.
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.
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.
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.
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.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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WNK3

Function

References

Further reading