Details of the Target

General Information of Target

Target ID LDTP10447
Target Name Serine/threonine-protein kinase WNK4 (WNK4)
Gene Name WNK4
Gene ID 65266
Synonyms
PRKWNK4; Serine/threonine-protein kinase WNK4; EC 2.7.11.1; Protein kinase lysine-deficient 4; Protein kinase with no lysine 4
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAAAPGGSAQPAGPGPRLGFSTADSGVGMSGLNPGPAVPMKDHDAIKLFVGQIPRGLDEQ
DLKPLFEEFGRIYELTVLKDRLTGLHKGCAFLTYCARDSALKAQSALHEQKTLPGMNRPI
QVKPAASEGRGEDRKLFVGMLGKQQGEEDVRRLFQPFGHIEECTVLRSPDGTSKGCAFVK
FGSQGEAQAAIRGLHGSRTMAGASSSLVVKLADTDRERALRRMQQMAGHLGAFHPAPLPL
GACGAYTTAILQHQAALLAAAQGPGLGPVAAVAAQMQHVAAFSLVAAPLLPAAAANSPPG
SGPGTLPGLPAPIGVNGFGPLTPQTNGQPGSDTLYNNGLSPYPAQSPGVADPLQQAYAGM
HHYAAAYPSAYAPVSTAFPQQPSALPQQQREGPEGCNLFIYHLPQEFGDAELIQTFLPFG
AVVSAKVFVDRATNQSKCFGFVSFDNPTSAQTAIQAMNGFQIGMKRLKVQLKRPKDANRP
Y
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Ser/Thr protein kinase family, WNK subfamily
Subcellular location
Cell junction, tight junction
Function
Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure. The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity. Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK. Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process. Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis. Also inhbits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism. May also phosphorylate NEDD4L.
Uniprot ID
Q96J92
Ensemble ID
ENST00000246914.10
HGNC ID
HGNC:14544
ChEMBL ID
CHEMBL1795196

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 Deletion: p.G1098AfsTer6
SNV: p.A473V;p.R1075C		 .
HT SNV: p.E1027D .
IGROV1 SNV: p.P551T .
JHH6 SNV: p.E107V .
JURKAT SNV: p.A484V .
KMCH1 Substitution: p.E367Ter .
KYSE410 SNV: p.G1088R .
LN18 SNV: p.V251M .
MFE319 SNV: p.A920T .
NCIH1155 SNV: p.A119V; p.A213V .
NCIH2286 SNV: p.G48W .
NCIH661 SNV: p.S711R .
NUGC3 SNV: p.C364Y .
SW1990 SNV: p.E614Ter .
TOV21G SNV: p.E107D .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C77(4.10)  LDD3413  [1]
Acrolein
 Probe Info  		N.A.  LDD0217  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [2]
 LDCM0022  KB02 IPC-298 C77(1.42)  LDD2400  [1]
 LDCM0023  KB03 IPC-298 C77(1.97)  LDD2817  [1]
 LDCM0024  KB05 RVH-421 C77(4.10)  LDD3413  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Serine/threonine-protein kinase OSR1 (OXSR1) STE Ser/Thr protein kinase family O95747

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.