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WNK4 (human)

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: EC 2.7.11.1; Kinase, protein; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Other group; Wnk family Cellular Component: tight junction; cytoplasm Molecular Function: protein serine/threonine kinase activity; ATP binding Biological Process: protein localization; regulation of cellular process; protein kinase cascade; ion transport; chloride transport; protein amino acid phosphorylation 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®

Select Structure to View Below WNK4 2V3S - C/D=1015-1020 (human)

STRING  |  Scansite  |  KinBase  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  DISEASE 145260 601844  |  Source  |  UCSD-Nature  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	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

SS  SS: 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.	MS  MS: 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	1		R124-m1	KAAEDSArPELPDSA
0	1		S219-p	RAERQRFsEEVEMLK
0	1		S239-p	NIVRFYDsWKSVLRG
0	1		T314	NVFITGPTGSVKIGD
0	1		K328-u	DLGLATLkRAsFAKS
0	3		S331-p	LATLkRAsFAKSVIG
1	2		S335	kRAsFAKSVIGTPEF
0	1		K399	RKPNSFHKVKIPEVK
0	1		T679-p	PRSRLRVtsVSDQND
0	1		S680-p	RSRLRVtsVSDQNDR
0	1		S789	SNEELQSSTSLEHRS
0	2		S791	EELQSSTSLEHRSWT
0	1		T1151-p	KHLSEVEtLQtLQKK
0	1		T1154-p	SEVEtLQtLQKKEIE
4	1		S1190-p	SSRQRRLsKGsFPTS
0	1		S1193-p	QRRLsKGsFPTSRRN
1	1		S1201-p	FPTSRRNsLQRSEPP
2	10		S1217-p	PGIMRRNsLSGSStG
0	1		T1223-p	NsLSGSStGSQEQRA

	mouse
S47-p	PRRVRRFsGKAEPRP
S64	SRPSRRSSVDLGLLS
C121	VKAVDSACPELTGSS
S216	RAERQRFSEEVEMLK
S236	NIVRFYDSWKSVLRG
S311-p	NVFITGPsGSVKIGD
K325	DLGLATLKRAsFAKs
S328-p	LATLKRAsFAKsVIG
S332-p	KRAsFAKsVIGTPEF
K396-u	TKPNSFYkVKMPEVK
T675	PRSRLRVTSVSDQSD
S676	RSRLRVTSVSDQSDR
S781-p	PNAEPQRsIsPEQRS
S783-p	AEPQRsIsPEQRSWA
A1130	KHLSEVEALQTLQKK
T1133	SEVEALQTLQKKEIE
S1169-p	SCRQRRLsKGsFPTS
S1172-p	QRRLsKGsFPTSRRN
S1180	FPTSRRNSLQRSDLP
S1196-p	PGIMRRNsLSGSSTG
T1202	NsLSGSSTGSQEQRA

	rat
S47	PRRVRRFSGKAEPRP
S64	SRPSRRSSVDLGLLS
C121	VKAADSACPELTVSS
S216	RAERQRFSEEVEMLK
S236	NIVRFYDSWKSVLRG
S311	NVFITGPSGSVKIGD
K325	DLGLATLKRASFAKs
S328	LATLKRASFAKsVIG
S332-p	KRASFAKsVIGTPEF
K396	TKPNSFYKVKMPEVK
T675	PRSRLRVTSVSDQSD
S676	RSRLRVTSVSDQSDR
S781	SDAELQRSISPEQRS
S783	AELQRSISPEQRSWA
A1130	KHLSEVEALQTLQKK
T1133	SEVEALQTLQKKEIE
S1169	SCRQRRLSKGSFPTS
S1172	QRRLSKGSFPTSRRN
S1180	FPTSRRNSLQRSDLP
S1196-p	PGIMRRNsLSGSSTG
T1202	NsLSGSSTGSQEQRA

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