WNK4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: WNK4_HUMAN
• UniProt AC: Q96J92
• Protein Name: Serine/threonine-protein kinase WNK4 {ECO:0000305}
• Gene Name: WNK4 {ECO:0000312|HGNC:HGNC:14544}
• Organism: Homo sapiens (Human).
• Sequence Length: 1243
• Subcellular Localization: Cell junction, tight junction . Present exclusively in intercellular junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical collecting duct. WNK4 is part of the tight junction complex.
• Protein Description: 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. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity)..
• Protein Sequence: MLASPATETTVLMSQTEADLALRPPPPLGTAGQPRLGPPPRRARRFSGKAEPRPRSSRLSRRSSVDLGLLSSWSLPASPAPDPPDPPDSAGPGPARSPPPSSKEPPEGTWTEGAPVKAAEDSARPELPDSAVGPGSREPLRVPEAVALERRREQEEKEDMETQAVATSPDGRYLKFDIEIGRGSFKTVYRGLDTDTTVEVAWCELQTRKLSRAERQRFSEEVEMLKGLQHPNIVRFYDSWKSVLRGQVCIVLVTELMTSGTLKTYLRRFREMKPRVLQRWSRQILRGLHFLHSRVPPILHRDLKCDNVFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDEAVDVYAFGMCMLEMATSEYPYSECQNAAQIYRKVTSGRKPNSFHKVKIPEVKEIIEGCIRTDKNERFTIQDLLAHAFFREERGVHVELAEEDDGEKPGLKLWLRMEDARRGGRPRDNQAIEFLFQLGRDAAEEVAQEMVALGLVCEADYQPVARAVRERVAAIQRKREKLRKARELEALPPEPGPPPATVPMAPGPPSVFPPEPEEPEADQHQPFLFRHASYSSTTSDCETDGYLSSSGFLDASDPALQPPGGVPSSLAESHLCLPSAFALSIPRSGPGSDFSPGDSYASDAASGLSDVGEGMGQMRRPPGRNLRRRPRSRLRVTSVSDQNDRVVECQLQTHNSKMVTFRFDLDGDSPEEIAAAMVYNEFILPSERDGFLRRIREIIQRVETLLKRDTGPMEAAEDTLSPQEEPAPLPALPVPLPDPSNEELQSSTSLEHRSWTAFSTSSSSPGTPLSPGNPFSPGTPISPGPIFPITSPPCHPSPSPFSPISSQVSSNPSPHPTSSPLPFSSSTPEFPVPLSQCPWSSLPTTSPPTFSPTCSQVTLSSPFFPPCPSTSSFPSTTAAPLLSLASAFSLAVMTVAQSLLSPSPGLLSQSPPAPPSPLPSLPLPPPVAPGGQESPSPHTAEVESEASPPPARPLPGEARLAPISEEGKPQLVGRFQVTSSKEPAEPLPLQPTSPTLSGSPKPSTPQLTSESSDTEDSAGGGPETREALAESDRAAEGLGAGVEEEGDDGKEPQVGGSPQPLSHPSPVWMNYSYSSLCLSSEESESSGEDEEFWAELQSLRQKHLSEVETLQTLQKKEIEDLYSRLGKQPPPGIVAPAAMLSSRQRRLSKGSFPTSRRNSLQRSEPPGPGIMRRNSLSGSSTGSQEQRASKGVTFAGDVGRM

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
4	Phosphorylation	----MLASPATETTV ----CCCCCCCCCEE	27.92	24719451
9	Phosphorylation	LASPATETTVLMSQT CCCCCCCCEEEEECC	20.18	24719451
14	Phosphorylation	TETTVLMSQTEADLA CCCEEEEECCCHHHH	29.77	24719451
47	Phosphorylation	PRRARRFSGKAEPRP CCCHHCCCCCCCCCC	37.26	-
63	Phosphorylation	SSRLSRRSSVDLGLL CHHHHCCCCCCCCCH	33.34	28348404
64	Phosphorylation	SRLSRRSSVDLGLLS HHHHCCCCCCCCCHH	20.17	27251275
97	Phosphorylation	AGPGPARSPPPSSKE CCCCCCCCCCCCCCC	43.81	24114839
101	Phosphorylation	PARSPPPSSKEPPEG CCCCCCCCCCCCCCC	60.87	23186163
102	Phosphorylation	ARSPPPSSKEPPEGT CCCCCCCCCCCCCCC	46.97	23186163
109	Phosphorylation	SKEPPEGTWTEGAPV CCCCCCCCCCCCCCC	27.79	23186163
111	Phosphorylation	EPPEGTWTEGAPVKA CCCCCCCCCCCCCCC	25.12	23186163
124	Methylation	KAAEDSARPELPDSA CCCCHHCCCCCCCCC	29.22	12020049
157	Ubiquitination	RRREQEEKEDMETQA HHHHHHHHHHHHHHH	59.26	23576762
175	Ubiquitination	SPDGRYLKFDIEIGR CCCCCEEEEEEEECC	31.86	23576762
184	Phosphorylation	DIEIGRGSFKTVYRG EEEECCCCCEEEECC	23.39	28348404
186	Ubiquitination	EIGRGSFKTVYRGLD EECCCCCEEEECCCC	38.49	23576762
219	Phosphorylation	RAERQRFSEEVEMLK HHHHHHHHHHHHHHH	34.73	-
226	Ubiquitination	SEEVEMLKGLQHPNI HHHHHHHHCCCCCCC	57.15	23576762
226	Methylation	SEEVEMLKGLQHPNI HHHHHHHHCCCCCCC	57.15	23644510
239	Phosphorylation	NIVRFYDSWKSVLRG CCHHHHHHHHHHHHH	25.65	-
241	Ubiquitination	VRFYDSWKSVLRGQV HHHHHHHHHHHHHCC	34.34	23576762
259	Phosphorylation	LVTELMTSGTLKTYL EEEHHHCCCHHHHHH	18.80	24719451
261	Phosphorylation	TELMTSGTLKTYLRR EHHHCCCHHHHHHHH	25.50	24719451
314	Phosphorylation	NVFITGPTGSVKIGD CEEEECCCCCEEECH	43.35	28122231
316	Phosphorylation	FITGPTGSVKIGDLG EEECCCCCEEECHHH	23.79	28122231
326	Phosphorylation	IGDLGLATLKRASFA ECHHHHHHHHHHHHH	37.54	21406692
328	Ubiquitination	DLGLATLKRASFAKS HHHHHHHHHHHHHHH	41.38	30230243
331	Phosphorylation	LATLKRASFAKSVIG HHHHHHHHHHHHHHC	29.75	21712546
335	Phosphorylation	KRASFAKSVIGTPEF HHHHHHHHHHCCCHH	18.61	25159151
339	Phosphorylation	FAKSVIGTPEFMAPE HHHHHHCCCHHHCHH	14.44	20639409
348	Phosphorylation	EFMAPEMYEEKYDEA HHHCHHHHHHHHHHH	21.19	20639409
370	Phosphorylation	MCMLEMATSEYPYSE HHHHHHHHCCCCHHH	22.30	26552605
371	Phosphorylation	CMLEMATSEYPYSEC HHHHHHHCCCCHHHH	26.12	26552605
373	Phosphorylation	LEMATSEYPYSECQN HHHHHCCCCHHHHHC	13.77	26552605
375	Phosphorylation	MATSEYPYSECQNAA HHHCCCCHHHHHCHH	19.05	26552605
376	Phosphorylation	ATSEYPYSECQNAAQ HHCCCCHHHHHCHHH	27.65	26552605
385	Phosphorylation	CQNAAQIYRKVTSGR HHCHHHHHHHHHCCC	7.72	26552605
387	Ubiquitination	NAAQIYRKVTSGRKP CHHHHHHHHHCCCCC	32.66	23576762
393	Ubiquitination	RKVTSGRKPNSFHKV HHHHCCCCCCCCCCC	52.67	23576762
450	Ubiquitination	AEEDDGEKPGLKLWL EECCCCCCCCCEEEE	50.33	23576762
454	Ubiquitination	DGEKPGLKLWLRMED CCCCCCCEEEEEHHH	43.46	23576762
575	Phosphorylation	PFLFRHASYSSTTSD CEEEEECCCCCCCCC	21.30	-
626	Phosphorylation	LPSAFALSIPRSGPG CCCHHEECCCCCCCC	27.41	24719451
679	Phosphorylation	PRSRLRVTSVSDQND CCHHEEEEECCCCCC	19.58	26852163
680	Phosphorylation	RSRLRVTSVSDQNDR CHHEEEEECCCCCCC	19.43	28857561
682	Phosphorylation	RLRVTSVSDQNDRVV HEEEEECCCCCCCEE	32.99	26852163
702	Phosphorylation	THNSKMVTFRFDLDG ECCCCEEEEEEECCC	12.95	24719451
728	Phosphorylation	YNEFILPSERDGFLR HCCCCCCCCCCHHHH	41.64	24719451
1010	Ubiquitination	APISEEGKPQLVGRF EECCCCCCCCEEEEE	32.63	23576762
1034	Phosphorylation	EPLPLQPTSPTLSGS CCCCCCCCCCCCCCC	34.08	27251275
1035	Phosphorylation	PLPLQPTSPTLSGSP CCCCCCCCCCCCCCC	23.67	26657352
1053	Phosphorylation	TPQLTSESSDTEDSA CCCCCCCCCCCCCCC	33.03	27251275
1054	Phosphorylation	PQLTSESSDTEDSAG CCCCCCCCCCCCCCC	44.49	27251275
1056	Phosphorylation	LTSESSDTEDSAGGG CCCCCCCCCCCCCCC	43.57	27251275
1113	Phosphorylation	PSPVWMNYSYSSLCL CCCCEECCCCHHEEC	7.90	-
1115	Phosphorylation	PVWMNYSYSSLCLSS CCEECCCCHHEECCC	7.60	-
1144	Ubiquitination	ELQSLRQKHLSEVET HHHHHHHHHHHHHHH	39.83	23576762
1151	Phosphorylation	KHLSEVETLQTLQKK HHHHHHHHHHHHHHH	29.37	-
1154	Phosphorylation	SEVETLQTLQKKEIE HHHHHHHHHHHHHHH	33.98	-
1157	Ubiquitination	ETLQTLQKKEIEDLY HHHHHHHHHHHHHHH	56.33	23576762
1158	Ubiquitination	TLQTLQKKEIEDLYS HHHHHHHHHHHHHHH	51.46	23576762
1164	Phosphorylation	KKEIEDLYSRLGKQP HHHHHHHHHHHCCCC	12.22	-
1165	Phosphorylation	KEIEDLYSRLGKQPP HHHHHHHHHHCCCCC	28.46	24719451
1190	Phosphorylation	SSRQRRLSKGSFPTS HHHHHHHHCCCCCCH	32.91	22817900
1201	Phosphorylation	FPTSRRNSLQRSEPP CCCHHHHCCCCCCCC	24.86	-
1217	Phosphorylation	PGIMRRNSLSGSSTG CCCCCCCCCCCCCCC	23.31	28355574
1219	Phosphorylation	IMRRNSLSGSSTGSQ CCCCCCCCCCCCCCH	36.13	28450419
1221	Phosphorylation	RRNSLSGSSTGSQEQ CCCCCCCCCCCCHHH	22.73	28450419
1222	Phosphorylation	RNSLSGSSTGSQEQR CCCCCCCCCCCHHHH	40.07	28450419
1223	Phosphorylation	NSLSGSSTGSQEQRA CCCCCCCCCCHHHHH	42.42	28450419
1225	Phosphorylation	LSGSSTGSQEQRASK CCCCCCCCHHHHHHC	30.54	28450419

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
335	S	Phosphorylation	Kinase	WNK4	Q96J92	PSP
575	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
575	S	Phosphorylation	Kinase	MAPKAPK3	Q3UMW7	PSP
575	S	Phosphorylation	Kinase	MAPKAPK5	O54992	PSP
1113	Y	Phosphorylation	Kinase	SRC	P12931	PSP
1115	Y	Phosphorylation	Kinase	SRC	P12931	PSP
1164	Y	Phosphorylation	Kinase	SRC	P12931	PSP
1190	S	Phosphorylation	Kinase	SGK1	O00141	PSP
1201	S	Phosphorylation	Kinase	SGK1	O00141	PSP
1217	S	Phosphorylation	Kinase	SGK1	O00141	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	KLHL3	Q9UH77	PMID:23453970
-	K	Ubiquitination	E3 ubiquitin ligase	KLHL2	O95198	PMID:23838290

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of WNK4_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of WNK4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NED4L_HUMAN	NEDD4L	physical	20525693
SGK1_HUMAN	SGK1	physical	20525693
KLHL3_HUMAN	KLHL3	physical	23453970
CUL3_HUMAN	CUL3	physical	23453970
KLHL3_HUMAN	KLHL3	physical	23576762
CUL3_HUMAN	CUL3	physical	23576762
KLHL3_HUMAN	KLHL3	physical	26435498
KLHL3_HUMAN	KLHL3	physical	23665031

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 614491: Pseudohypoaldosteronism 2B (PHA2B)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.