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Protein

Serine/threonine-protein kinase WNK4

Gene

WNK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei186 – 1861ATPPROSITE-ProRule annotation
Active sitei302 – 3021Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi180 – 1889ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. chloride channel inhibitor activity Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. chloride transport Source: Ensembl
  2. distal tubule morphogenesis Source: UniProtKB
  3. intracellular signal transduction Source: UniProtKB
  4. ion homeostasis Source: UniProtKB
  5. ion transport Source: UniProtKB
  6. negative regulation of pancreatic juice secretion Source: Ensembl
  7. protein localization Source: Ensembl
  8. protein phosphorylation Source: UniProtKB
  9. regulation of cellular process Source: UniProtKB
  10. renal sodium ion absorption Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_160189. Stimuli-sensing channels.
SignaLinkiQ96J92.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK4 (EC:2.7.11.1)
Alternative name(s):
Protein kinase lysine-deficient 4
Protein kinase with no lysine 4
Gene namesi
Name:WNK4
Synonyms:PRKWNK4
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:14544. WNK4.

Subcellular locationi

  1. Cell junctiontight junction By similarity

  2. Note: 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 (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. tight junction Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Tight junction

Pathology & Biotechi

Involvement in diseasei

Pseudohypoaldosteronism 2B (PHA2B)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.

See also OMIM:614491
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti562 – 5621E → K in PHA2B; impaired interaction with KLHL3. 3 Publications
VAR_017588
Natural varianti564 – 5641D → A in PHA2B; impaired interaction with KLHL3. 2 Publications
VAR_017589
Natural varianti565 – 5651Q → E in PHA2B; impaired interaction with KLHL3. 3 Publications
VAR_017590
Natural varianti1185 – 11851R → C in PHA2B. 1 Publication
VAR_017591

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614491. phenotype.
Orphaneti88939. Pseudohypoaldosteronism type 2B.
PharmGKBiPA134875400.

Polymorphism and mutation databases

BioMutaiWNK4.
DMDMi41688789.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12431243Serine/threonine-protein kinase WNK4PRO_0000086824Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki157 – 157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki175 – 175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki186 – 186Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki226 – 226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki241 – 241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki328 – 328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei331 – 3311Phosphoserine; by autocatalysisBy similarity
Modified residuei335 – 3351Phosphoserine; by autocatalysisBy similarity
Cross-linki387 – 387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki393 – 393Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki450 – 450Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki454 – 454Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1010 – 1010Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1144 – 1144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1157 – 1157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1158 – 1158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Phosphorylated by WNK1 and WNK3.By similarity
Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation and increased expression of KCNJ1 at the cell surface. Ubiquitinated by the BCR(KLHL2) complex.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ96J92.
PaxDbiQ96J92.
PRIDEiQ96J92.

PTM databases

PhosphoSiteiQ96J92.

Expressioni

Tissue specificityi

Expressed in kidney, colon and skin.1 Publication

Gene expression databases

BgeeiQ96J92.
CleanExiHS_WNK4.
ExpressionAtlasiQ96J92. baseline and differential.
GenevestigatoriQ96J92.

Organism-specific databases

HPAiHPA016500.

Interactioni

Subunit structurei

Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). Interacts with KLHL3.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
OXSR1O9574711EBI-766352,EBI-620853

Protein-protein interaction databases

BioGridi122421. 12 interactions.
IntActiQ96J92. 6 interactions.
MINTiMINT-5207492.
STRINGi9606.ENSP00000246914.

Structurei

Secondary structure

1
1243
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi562 – 5643Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2V3SX-ray1.70C/D1015-1020[»]
4CH9X-ray1.84C/D557-567[»]
4CHBX-ray1.56C/D557-567[»]
ProteinModelPortaliQ96J92.
SMRiQ96J92. Positions 132-523.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96J92.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini174 – 432259Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074385.
HOGENOMiHOG000230962.
HOVERGENiHBG050347.
InParanoidiQ96J92.
KOiK08867.
OMAiISPGPIF.
OrthoDBiEOG7KDF8Z.
PhylomeDBiQ96J92.
TreeFamiTF315363.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1Curated1 Publication (identifier: Q96J92-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLASPATETT VLMSQTEADL ALRPPPPLGT AGQPRLGPPP RRARRFSGKA
60 70 80 90 100
EPRPRSSRLS RRSSVDLGLL SSWSLPASPA PDPPDPPDSA GPGPARSPPP
110 120 130 140 150
SSKEPPEGTW TEGAPVKAAE DSARPELPDS AVGPGSREPL RVPEAVALER
160 170 180 190 200
RREQEEKEDM ETQAVATSPD GRYLKFDIEI GRGSFKTVYR GLDTDTTVEV
210 220 230 240 250
AWCELQTRKL SRAERQRFSE EVEMLKGLQH PNIVRFYDSW KSVLRGQVCI
260 270 280 290 300
VLVTELMTSG TLKTYLRRFR EMKPRVLQRW SRQILRGLHF LHSRVPPILH
310 320 330 340 350
RDLKCDNVFI TGPTGSVKIG DLGLATLKRA SFAKSVIGTP EFMAPEMYEE
360 370 380 390 400
KYDEAVDVYA FGMCMLEMAT SEYPYSECQN AAQIYRKVTS GRKPNSFHKV
410 420 430 440 450
KIPEVKEIIE GCIRTDKNER FTIQDLLAHA FFREERGVHV ELAEEDDGEK
460 470 480 490 500
PGLKLWLRME DARRGGRPRD NQAIEFLFQL GRDAAEEVAQ EMVALGLVCE
510 520 530 540 550
ADYQPVARAV RERVAAIQRK REKLRKAREL EALPPEPGPP PATVPMAPGP
560 570 580 590 600
PSVFPPEPEE PEADQHQPFL FRHASYSSTT SDCETDGYLS SSGFLDASDP
610 620 630 640 650
ALQPPGGVPS SLAESHLCLP SAFALSIPRS GPGSDFSPGD SYASDAASGL
660 670 680 690 700
SDVGEGMGQM RRPPGRNLRR RPRSRLRVTS VSDQNDRVVE CQLQTHNSKM
710 720 730 740 750
VTFRFDLDGD SPEEIAAAMV YNEFILPSER DGFLRRIREI IQRVETLLKR
760 770 780 790 800
DTGPMEAAED TLSPQEEPAP LPALPVPLPD PSNEELQSST SLEHRSWTAF
810 820 830 840 850
STSSSSPGTP LSPGNPFSPG TPISPGPIFP ITSPPCHPSP SPFSPISSQV
860 870 880 890 900
SSNPSPHPTS SPLPFSSSTP EFPVPLSQCP WSSLPTTSPP TFSPTCSQVT
910 920 930 940 950
LSSPFFPPCP STSSFPSTTA APLLSLASAF SLAVMTVAQS LLSPSPGLLS
960 970 980 990 1000
QSPPAPPSPL PSLPLPPPVA PGGQESPSPH TAEVESEASP PPARPLPGEA
1010 1020 1030 1040 1050
RLAPISEEGK PQLVGRFQVT SSKEPAEPLP LQPTSPTLSG SPKPSTPQLT
1060 1070 1080 1090 1100
SESSDTEDSA GGGPETREAL AESDRAAEGL GAGVEEEGDD GKEPQVGGSP
1110 1120 1130 1140 1150
QPLSHPSPVW MNYSYSSLCL SSEESESSGE DEEFWAELQS LRQKHLSEVE
1160 1170 1180 1190 1200
TLQTLQKKEI EDLYSRLGKQ PPPGIVAPAA MLSSRQRRLS KGSFPTSRRN
1210 1220 1230 1240
SLQRSEPPGP GIMRRNSLSG SSTGSQEQRA SKGVTFAGDV GRM
Length:1,243
Mass (Da):134,739
Last modified:December 1, 2001 - v1
Checksum:iBAC35F0098BA3391
GO
Isoform 2Curated (identifier: Q96J92-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-228: Missing.
     229-264: QHPNIVRFYDSWKSVLRGQVCIVLVTELMTSGTLKT → MRRRQQGAAGGNFPVGGSFPEDVSPHQDSGYAPSPR
     828-1210: Missing.
     1233-1243: GVTFAGDVGRM → EAGQRPGKLWLRATVQLRVWGLELRRKEMMGRNPKLGAAPNP

Note: No experimental confirmation available.Curated

Show »
Length:663
Mass (Da):73,370
Checksum:i6711A9D6CEFD8146
GO
Isoform 3Curated (identifier: Q96J92-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1145-1165: HLSEVETLQTLQKKEIEDLYS → PFHALRASSGTCQRWKHYRHY
     1166-1243: Missing.

Note: No experimental confirmation available. Incomplete sequence.Curated

Show »
Length:1,165
Mass (Da):126,577
Checksum:i87D926F2D3141A1B
GO

Sequence cautioni

The sequence BAC04669.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAC48387.1 differs from that shown. Reason: Frameshift at position 4. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti525 – 5251R → C in BAC04688 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti434 – 4341E → D in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
VAR_041330
Natural varianti562 – 5621E → K in PHA2B; impaired interaction with KLHL3. 3 Publications
VAR_017588
Natural varianti564 – 5641D → A in PHA2B; impaired interaction with KLHL3. 2 Publications
VAR_017589
Natural varianti565 – 5651Q → E in PHA2B; impaired interaction with KLHL3. 3 Publications
VAR_017590
Natural varianti601 – 6011A → S.
Corresponds to variant rs55781437 [ dbSNP | Ensembl ].
VAR_061748
Natural varianti677 – 6771R → W.
Corresponds to variant rs9896991 [ dbSNP | Ensembl ].
VAR_051685
Natural varianti813 – 8131P → L.1 Publication
VAR_041331
Natural varianti961 – 9611P → S.
Corresponds to variant rs2290041 [ dbSNP | Ensembl ].
VAR_051686
Natural varianti992 – 9921P → S in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_041332
Natural varianti1013 – 10131L → P.1 Publication
VAR_041333
Natural varianti1185 – 11851R → C in PHA2B. 1 Publication
VAR_017591

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 228228Missing in isoform 2. 1 PublicationVSP_050648Add
BLAST
Alternative sequencei229 – 26436QHPNI…GTLKT → MRRRQQGAAGGNFPVGGSFP EDVSPHQDSGYAPSPR in isoform 2. 1 PublicationVSP_050649Add
BLAST
Alternative sequencei828 – 1210383Missing in isoform 2. 1 PublicationVSP_050650Add
BLAST
Alternative sequencei1145 – 116521HLSEV…EDLYS → PFHALRASSGTCQRWKHYRH Y in isoform 3. 1 PublicationVSP_050652Add
BLAST
Alternative sequencei1166 – 124378Missing in isoform 3. 1 PublicationVSP_050653Add
BLAST
Alternative sequencei1233 – 124311GVTFAGDVGRM → EAGQRPGKLWLRATVQLRVW GLELRRKEMMGRNPKLGAAP NP in isoform 2. 1 PublicationVSP_050651Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF390018 mRNA. Translation: AAK91995.1.
AJ316534 mRNA. Translation: CAC48387.1. Frameshift.
AK096003 mRNA. Translation: BAC04669.1. Different initiation.
AK096052 mRNA. Translation: BAC04688.1.
EU332870 Genomic DNA. Translation: ABY87559.1.
CH471152 Genomic DNA. Translation: EAW60881.1.
CH471152 Genomic DNA. Translation: EAW60882.1.
BC136664 mRNA. Translation: AAI36665.1.
AJ309861 mRNA. Translation: CAC32991.1.
CCDSiCCDS11439.1. [Q96J92-1]
RefSeqiNP_115763.2. NM_032387.4. [Q96J92-1]
UniGeneiHs.105448.

Genome annotation databases

GeneIDi65266.
KEGGihsa:65266.
UCSCiuc002ibj.3. human. [Q96J92-1]

Polymorphism and mutation databases

BioMutaiWNK4.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF390018 mRNA. Translation: AAK91995.1.
AJ316534 mRNA. Translation: CAC48387.1. Frameshift.
AK096003 mRNA. Translation: BAC04669.1. Different initiation.
AK096052 mRNA. Translation: BAC04688.1.
EU332870 Genomic DNA. Translation: ABY87559.1.
CH471152 Genomic DNA. Translation: EAW60881.1.
CH471152 Genomic DNA. Translation: EAW60882.1.
BC136664 mRNA. Translation: AAI36665.1.
AJ309861 mRNA. Translation: CAC32991.1.
CCDSiCCDS11439.1. [Q96J92-1]
RefSeqiNP_115763.2. NM_032387.4. [Q96J92-1]
UniGeneiHs.105448.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2V3SX-ray1.70C/D1015-1020[»]
4CH9X-ray1.84C/D557-567[»]
4CHBX-ray1.56C/D557-567[»]
ProteinModelPortaliQ96J92.
SMRiQ96J92. Positions 132-523.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122421. 12 interactions.
IntActiQ96J92. 6 interactions.
MINTiMINT-5207492.
STRINGi9606.ENSP00000246914.

Chemistry

ChEMBLiCHEMBL1795196.

PTM databases

PhosphoSiteiQ96J92.

Polymorphism and mutation databases

BioMutaiWNK4.
DMDMi41688789.

Proteomic databases

MaxQBiQ96J92.
PaxDbiQ96J92.
PRIDEiQ96J92.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65266.
KEGGihsa:65266.
UCSCiuc002ibj.3. human. [Q96J92-1]

Organism-specific databases

CTDi65266.
GeneCardsiGC17P040932.
GeneReviewsiWNK4.
HGNCiHGNC:14544. WNK4.
HPAiHPA016500.
MIMi601844. gene.
614491. phenotype.
neXtProtiNX_Q96J92.
Orphaneti88939. Pseudohypoaldosteronism type 2B.
PharmGKBiPA134875400.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074385.
HOGENOMiHOG000230962.
HOVERGENiHBG050347.
InParanoidiQ96J92.
KOiK08867.
OMAiISPGPIF.
OrthoDBiEOG7KDF8Z.
PhylomeDBiQ96J92.
TreeFamiTF315363.

Enzyme and pathway databases

ReactomeiREACT_160189. Stimuli-sensing channels.
SignaLinkiQ96J92.

Miscellaneous databases

ChiTaRSiWNK4. human.
EvolutionaryTraceiQ96J92.
GeneWikiiWNK4.
GenomeRNAii65266.
NextBioi67398.
PROiQ96J92.
SOURCEiSearch...

Gene expression databases

BgeeiQ96J92.
CleanExiHS_WNK4.
ExpressionAtlasiQ96J92. baseline and differential.
GenevestigatoriQ96J92.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE, VARIANTS PHA2B LYS-562; ALA-564; GLU-565 AND CYS-1185.
    Tissue: KidneyImported.
  2. Chistiakov D.A.
    Thesis (2001), College de France / Paris, France
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: KidneyImported.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 504-1165 (ISOFORM 3).
    Tissue: Kidney.
  4. NHLBI resequencing and genotyping service (RS&G)
    Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  7. "WNK kinases, a novel protein kinase subfamily in multi-cellular organisms."
    Verissimo F., Jordan P.
    Oncogene 20:5562-5569(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 207-418 (ISOFORMS 1/3), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION.
    Tissue: ColonImported.
  8. "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members."
    Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S., Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.
    J. Biol. Chem. 285:25161-25167(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. Cited for: UBIQUITINATION BY KLHL2.
  10. "The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction."
    Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A., Macartney T.J., Wood N.T., Alessi D.R., Kurz T.
    Biochem. J. 451:111-122(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLHL3, CHARACTERIZATION OF VARIANTS PHA2B LYS-562 AND GLU-565.
  11. Cited for: UBIQUITINATION, INTERACTION WITH KLHL3, CHARACTERIZATION OF VARIANT PHA2B ALA-564.
  12. "Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation."
    Wu G., Peng J.B.
    FEBS Lett. 587:1717-1722(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLHL3.
  13. "Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4."
    Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.
    Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION AT LYS-157; LYS-175; LYS-186; LYS-226; LYS-241; LYS-328; LYS-387; LYS-393; LYS-450; LYS-454; LYS-1010; LYS-1144; LYS-1157 AND LYS-1158, INTERACTION WITH KLHL3, CHARACTERIZATION OF VARIANTS PHA2B LYS-562 AND GLU-565.
  14. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-434; LEU-813; SER-992 AND PRO-1013.

Entry informationi

Entry nameiWNK4_HUMAN
AccessioniPrimary (citable) accession number: Q96J92
Secondary accession number(s): B0LPI0
, Q8N8X3, Q8N8Z2, Q96DT8, Q9BYS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: December 1, 2001
Last modified: April 29, 2015
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Cys-203 is present instead of the conserved Lys which is expected to be an active site residue. Lys-186 appears to fulfill the required catalytic function.By similarity

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.