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Q96J92

- WNK4_HUMAN

UniProt

Q96J92 - WNK4_HUMAN

Protein

Serine/threonine-protein kinase WNK4

Gene

WNK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    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

    Magnesium.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: UniProt
    3. protein binding Source: UniProtKB
    4. 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

    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: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:14544. WNK4.

    Subcellular locationi

    Cell junctiontight junction By similarity
    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

    Keywords - Cellular componenti

    Cell junction, Tight junction

    Pathology & Biotechi

    Involvement in diseasei

    Pseudohypoaldosteronism 2B (PHA2B) [MIM:614491]: An autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti562 – 5621E → K in PHA2B; impaired interaction with KLHL3. 1 Publication
    VAR_017588
    Natural varianti564 – 5641D → A in PHA2B; impaired interaction with KLHL3. 1 Publication
    VAR_017589
    Natural varianti565 – 5651Q → E in PHA2B; impaired interaction with KLHL3. 1 Publication
    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.

    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

    ArrayExpressiQ96J92.
    BgeeiQ96J92.
    CleanExiHS_WNK4.
    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 – 5643

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000230962.
    HOVERGENiHBG050347.
    InParanoidiQ96J92.
    KOiK08867.
    OMAiESHLRLP.
    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. Align

    Isoform 11 PublicationCurated (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

    MLASPATETT VLMSQTEADL ALRPPPPLGT AGQPRLGPPP RRARRFSGKA     50
    EPRPRSSRLS RRSSVDLGLL SSWSLPASPA PDPPDPPDSA GPGPARSPPP 100
    SSKEPPEGTW TEGAPVKAAE DSARPELPDS AVGPGSREPL RVPEAVALER 150
    RREQEEKEDM ETQAVATSPD GRYLKFDIEI GRGSFKTVYR GLDTDTTVEV 200
    AWCELQTRKL SRAERQRFSE EVEMLKGLQH PNIVRFYDSW KSVLRGQVCI 250
    VLVTELMTSG TLKTYLRRFR EMKPRVLQRW SRQILRGLHF LHSRVPPILH 300
    RDLKCDNVFI TGPTGSVKIG DLGLATLKRA SFAKSVIGTP EFMAPEMYEE 350
    KYDEAVDVYA FGMCMLEMAT SEYPYSECQN AAQIYRKVTS GRKPNSFHKV 400
    KIPEVKEIIE GCIRTDKNER FTIQDLLAHA FFREERGVHV ELAEEDDGEK 450
    PGLKLWLRME DARRGGRPRD NQAIEFLFQL GRDAAEEVAQ EMVALGLVCE 500
    ADYQPVARAV RERVAAIQRK REKLRKAREL EALPPEPGPP PATVPMAPGP 550
    PSVFPPEPEE PEADQHQPFL FRHASYSSTT SDCETDGYLS SSGFLDASDP 600
    ALQPPGGVPS SLAESHLCLP SAFALSIPRS GPGSDFSPGD SYASDAASGL 650
    SDVGEGMGQM RRPPGRNLRR RPRSRLRVTS VSDQNDRVVE CQLQTHNSKM 700
    VTFRFDLDGD SPEEIAAAMV YNEFILPSER DGFLRRIREI IQRVETLLKR 750
    DTGPMEAAED TLSPQEEPAP LPALPVPLPD PSNEELQSST SLEHRSWTAF 800
    STSSSSPGTP LSPGNPFSPG TPISPGPIFP ITSPPCHPSP SPFSPISSQV 850
    SSNPSPHPTS SPLPFSSSTP EFPVPLSQCP WSSLPTTSPP TFSPTCSQVT 900
    LSSPFFPPCP STSSFPSTTA APLLSLASAF SLAVMTVAQS LLSPSPGLLS 950
    QSPPAPPSPL PSLPLPPPVA PGGQESPSPH TAEVESEASP PPARPLPGEA 1000
    RLAPISEEGK PQLVGRFQVT SSKEPAEPLP LQPTSPTLSG SPKPSTPQLT 1050
    SESSDTEDSA GGGPETREAL AESDRAAEGL GAGVEEEGDD GKEPQVGGSP 1100
    QPLSHPSPVW MNYSYSSLCL SSEESESSGE DEEFWAELQS LRQKHLSEVE 1150
    TLQTLQKKEI EDLYSRLGKQ PPPGIVAPAA MLSSRQRRLS KGSFPTSRRN 1200
    SLQRSEPPGP GIMRRNSLSG SSTGSQEQRA SKGVTFAGDV GRM 1243
    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 CAC48387.1 differs from that shown. Reason: Frameshift at position 4.
    The sequence BAC04669.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    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. 1 Publication
    VAR_017588
    Natural varianti564 – 5641D → A in PHA2B; impaired interaction with KLHL3. 1 Publication
    VAR_017589
    Natural varianti565 – 5651Q → E in PHA2B; impaired interaction with KLHL3. 1 Publication
    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:
    EMBL
    GenBank
    DDBJ
    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 databases

    DMDMi41688789.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS11439.1. [Q96J92-1 ]
    RefSeqi NP_115763.2. NM_032387.4. [Q96J92-1 ]
    UniGenei Hs.105448.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2V3S X-ray 1.70 C/D 1015-1020 [» ]
    4CH9 X-ray 1.84 C/D 557-567 [» ]
    4CHB X-ray 1.56 C/D 557-567 [» ]
    ProteinModelPortali Q96J92.
    SMRi Q96J92. Positions 132-523.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122421. 12 interactions.
    IntActi Q96J92. 6 interactions.
    MINTi MINT-5207492.
    STRINGi 9606.ENSP00000246914.

    Chemistry

    ChEMBLi CHEMBL1795196.

    PTM databases

    PhosphoSitei Q96J92.

    Polymorphism databases

    DMDMi 41688789.

    Proteomic databases

    MaxQBi Q96J92.
    PaxDbi Q96J92.
    PRIDEi Q96J92.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 65266.
    KEGGi hsa:65266.
    UCSCi uc002ibj.3. human. [Q96J92-1 ]

    Organism-specific databases

    CTDi 65266.
    GeneCardsi GC17P040932.
    GeneReviewsi WNK4.
    HGNCi HGNC:14544. WNK4.
    HPAi HPA016500.
    MIMi 601844. gene.
    614491. phenotype.
    neXtProti NX_Q96J92.
    Orphaneti 88939. Pseudohypoaldosteronism type 2B.
    PharmGKBi PA134875400.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230962.
    HOVERGENi HBG050347.
    InParanoidi Q96J92.
    KOi K08867.
    OMAi ESHLRLP.
    OrthoDBi EOG7KDF8Z.
    PhylomeDBi Q96J92.
    TreeFami TF315363.

    Enzyme and pathway databases

    Reactomei REACT_160189. Stimuli-sensing channels.
    SignaLinki Q96J92.

    Miscellaneous databases

    ChiTaRSi WNK4. human.
    EvolutionaryTracei Q96J92.
    GeneWikii WNK4.
    GenomeRNAii 65266.
    NextBioi 67398.
    PROi Q96J92.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96J92.
    Bgeei Q96J92.
    CleanExi HS_WNK4.
    Genevestigatori Q96J92.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR024678. Kinase_OSR1/WNK_CCT.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF12202. OSR1_C. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 2 hits.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 130 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

    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