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Protein Page:
WNK4 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
WNK4 Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L. Interacts with the C-terminal region of KCNJ1. Interacts with WNK1 and WNK3. Expressed in kidney, colon and skin. Activation requires autophosphorylation of Ser- 335. Phosphorylation of Ser-331 also promotes increased activity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 2.7.11.1; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Other group; Wnk family
Chromosomal Location of Human Ortholog: 17q21-q22
Cellular Component: tight junction; cytoplasm
Molecular Function: protein serine/threonine kinase activity; protein binding; chloride channel inhibitor activity; ATP binding
Biological Process: protein localization; ion homeostasis; regulation of cellular process; chloride transport; ion transport; protein amino acid phosphorylation
Disease: Pseudohypoaldosteronism, Type Iib
Reference #:  Q96J92 (UniProtKB)
Alt. Names/Synonyms: PHA2B; PRKWNK4; Protein kinase lysine-deficient 4; Protein kinase with no lysine 4; Serine/threonine-protein kinase WNK4; WNK lysine deficient protein kinase 4; WNK4
Gene Symbols: WNK4
Molecular weight: 134,739 Da
Basal Isoelectric point: 5.36  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

WNK4

Protein Structure Not Found.


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Sites Implicated In
activity, inhibited: Y1113‑p, Y1115‑p
molecular association, regulation: Y1164‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 2 S47-p PRRARRFsGKAEPRP
0 1 S64-p SRLSRRSsVDLGLLS
0 2 S97-p AGPGPARsPPPSSKE
0 1 R124-m1 KAAEDSArPELPDSA
1 0 K157 RRREQEEKEDMETQA
1 0 K175 SPDGRYLKFDIEIGR
1 0 K186 EIGRGSFKTVYRGLD
0 1 S219-p RAERQRFsEEVEMLk
0 1 K226-m1 sEEVEMLkGLQHPNI
1 0 K226 sEEVEMLKGLQHPNI
0 1 S239-p NIVRFYDsWKSVLRG
1 0 K241 VRFYDsWKSVLRGQV
0 1 T314 NVFITGPTGSVKIGD
1 1 K328-ub DLGLATLkRAsFAKs
0 4 S331-p LATLkRAsFAKsVIG
2 5 S335-p kRAsFAKsVIGTPEF
1 0 K387 NAAQIYRKVTSGRKP
1 0 K393 RKVTSGRKPNSFHKV
0 1 K399 RKPNSFHKVKIPEVK
1 0 K450 AEEDDGEKPGLKLWL
1 0 K454 DGEKPGLKLWLRMED
1 0 R666 QMRRPPGRNLRRRPR
0 1 T679-p PRSRLRVtsVSDQND
0 2 S680-p RSRLRVtsVSDQNDR
0 1 S789 SNEELQSSTSLEHRS
0 4 S791 EELQSSTSLEHRSWT
1 0 K1010 APISEEGKPQLVGRF
0 4 S1035 PLPLQPTSPTLSGSP
0 1 S1073 TREALAESDRAAEGL
1 1 Y1113-p PSPVWMNySySSLCL
1 1 Y1115-p PVWMNySySSLCLSS
1 0 K1144 ELQSLRQKHLSEVEt
0 1 T1151-p KHLSEVEtLQtLQKK
0 1 T1154-p SEVEtLQtLQKKEIE
1 0 K1157 EtLQtLQKKEIEDLy
1 0 K1158 tLQtLQKKEIEDLyS
1 1 Y1164-p KKEIEDLySRLGKQP
5 2 S1190-p SSRQRRLsKGSFPTS
0 2 S1193 QRRLsKGSFPTSRRN
1 1 S1201-p FPTSRRNsLQRSEPP
4 15 S1217-p PGIMRRNsLSGSStG
0 1 T1223-p NsLSGSStGSQEQRA
  mouse

 
S47-p PRRVRRFsGKAEPRP
S64 SRPSRRSSVDLGLLS
S95-p DSAGPTRsPPSSSKE
C121 VKAVDSACPELTGSS
K154-ub RRREQEEkEDTETQA
K172-ub SPDGRYLkFDIEIGR
K183-ub EIGRGSFkTVYRGLD
S216 RAERQRFSEEVEMLk
K223 SEEVEMLKGLQHPNI
K223-ub SEEVEMLkGLQHPNI
S236 NIVRFYDSWkSVLRG
K238-ub VRFYDSWkSVLRGQV
S311-p NVFITGPsGSVKIGD
K325-ub DLGLATLkRAsFAKs
S328-p LATLkRAsFAKsVIG
S332-p kRAsFAKsVIGTPEF
K384-ub NAAQIYRkVTSGTkP
K390-ub RkVTSGTkPNSFYkV
K396-ub TkPNSFYkVKMPEVK
K447-ub AEEDDGEkPGLkLWL
K451-ub DGEkPGLkLWLRMED
K662-ub QMRKNPVkTLRRRPR
T675 PRSRLRVTsVSDQSD
S676-p RSRLRVTsVSDQSDR
S781-p PNAEPQRsIsPEQRS
S783-p AEPQRsIsPEQRSWA
K990-ub APISEEGkPQLVGRF
S1014-p EPPLQPAsPTLSRSL
S1052-p TREALAEsDRAAEGL
Y1092 PSPVWMNYSYSSLCL
Y1094 PVWMNYSYSSLCLSS
K1123-ub ELQNLRQkHLSEVEA
A1130 kHLSEVEALQTLQkk
T1133 SEVEALQTLQkkEIE
K1136-ub EALQTLQkkEIEDLY
K1137-ub ALQTLQkkEIEDLYS
Y1143 kkEIEDLYSRLGKQP
S1169-p SCRQRRLsKGsFPTS
S1172-p QRRLsKGsFPTSRRN
S1180 FPTSRRNSLQRSDLP
S1196-p PGIMRRNsLSGSSTG
T1202 NsLSGSSTGSQEQRA
  rat

 
S47 PRRVRRFSGKAEPRP
S64 SRPSRRSSVDLGLLS
S95 DSAGPMRSPPSNSKE
C121 VKAADSACPELTVSS
K154 RRREQEEKEDTETQA
K172 SPDGRYLKFDIEIGR
K183 EIGRGSFKTVYRGLD
S216 RAERQRFSEEVEMLK
K223 SEEVEMLKGLQHPNI
K223 SEEVEMLKGLQHPNI
S236 NIVRFYDSWKSVLRG
K238 VRFYDSWKSVLRGQV
S311 NVFITGPSGSVKIGD
K325 DLGLATLKRASFAKs
S328 LATLKRASFAKsVIG
S332-p KRASFAKsVIGTPEF
K384 NAAQIYRKVTSGTKP
K390 RKVTSGTKPNSFYKV
K396 TKPNSFYKVKMPEVK
K447 AEEDDGEKPGLKLWL
K451 DGEKPGLKLWLRMED
K662 QMRKNPVKTLRRRPR
T675 PRSRLRVTSVSDQSD
S676 RSRLRVTSVSDQSDR
S781 SDAELQRSISPEQRS
S783 AELQRSISPEQRSWA
K990 APISEEGKPQLVGRF
S1014-p EPPLQPAsPTLSRSL
S1052 TREALAESDRAAEGL
Y1092 PSPVWMNYSYSSLCL
Y1094 PVWMNYSYSSLCLSS
K1123 ELQNLRQKHLSEVEA
A1130 KHLSEVEALQTLQKK
T1133 SEVEALQTLQKKEIE
K1136 EALQTLQKKEIEDLY
K1137 ALQTLQKKEIEDLYS
Y1143 KKEIEDLYSRLGKQP
S1169 SCRQRRLSKGSFPTS
S1172 QRRLSKGSFPTSRRN
S1180 FPTSRRNSLQRSDLP
S1196-p PGIMRRNsLSGSSTG
T1202 NsLSGSSTGSQEQRA
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