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Q9BYP7

- WNK3_HUMAN

UniProt

Q9BYP7 - WNK3_HUMAN

Protein

Serine/threonine-protein kinase WNK3

Gene

WNK3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 3 (19 Oct 2011)
      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. Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca2+ influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.
    Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686, isoform 1 inhibits the activity of SLC12A3.

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activation requires autophosphorylation of Ser-308. Phosphorylation of Ser-304 also promotes increased activity By similarity. Kinase activity is inhibited by WNK4.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei159 – 1591ATPBy similarityPROSITE-ProRule annotation
    Active sitei275 – 2751Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi153 – 1619ATPBy similarityPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. chloride channel inhibitor activity Source: UniProt
    3. protein binding Source: IntAct
    4. protein kinase activity Source: BHF-UCL
    5. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. intracellular signal transduction Source: UniProtKB
    2. negative regulation of apoptotic process Source: UniProtKB
    3. positive regulation of calcium ion transport Source: UniProtKB
    4. positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
    5. positive regulation of ion transmembrane transporter activity Source: BHF-UCL
    6. positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    7. positive regulation of rubidium ion transmembrane transporter activity Source: UniProtKB
    8. positive regulation of rubidium ion transport Source: UniProtKB
    9. positive regulation of sodium ion transmembrane transporter activity Source: UniProtKB
    10. positive regulation of sodium ion transport Source: BHF-UCL
    11. protein autophosphorylation Source: BHF-UCL
    12. protein phosphorylation Source: UniProtKB
    13. regulation of ion homeostasis 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.
    SignaLinkiQ9BYP7.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase WNK3 (EC:2.7.11.1)
    Alternative name(s):
    Protein kinase lysine-deficient 3
    Protein kinase with no lysine 3
    Gene namesi
    Name:WNK3
    Synonyms:KIAA1566, PRKWNK3
    OrganismiHomo sapiens (Human)Imported
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome X

    Organism-specific databases

    HGNCiHGNC:14543. WNK3.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. adherens junction Source: BHF-UCL
    2. cytoplasm Source: UniProtKB
    3. tight junction Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi294 – 2941D → A: Catalytically inactive form. Inhibits sodium-coupled chloride cotransporters and activates potassium-coupled chloride cotransporters. 2 Publications

    Organism-specific databases

    PharmGKBiPA33784.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 18001800Serine/threonine-protein kinase WNK3PRO_0000086823Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei62 – 621Phosphoserine1 Publication
    Modified residuei304 – 3041Phosphoserine; by autocatalysisBy similarity
    Modified residuei308 – 3081Phosphoserine; by autocatalysisBy similarity

    Post-translational modificationi

    Ubiquitinated by the BCR(KLHL2) complex, leading to its degradation.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9BYP7.
    PaxDbiQ9BYP7.
    PRIDEiQ9BYP7.

    PTM databases

    PhosphoSiteiQ9BYP7.

    Expressioni

    Tissue specificityi

    Expressed in brain, lung, kidney, liver and pancreas, and in fetal tissues including placenta, fetal brain, lung and kidney. Very low levels of expression were also detected in fetal heart, thymus, liver and spleen. Isoform 1 is brain-specific. Isoform 3 is kidney-specific.3 Publications

    Gene expression databases

    ArrayExpressiQ9BYP7.
    BgeeiQ9BYP7.
    CleanExiHS_WNK3.
    GenevestigatoriQ9BYP7.

    Organism-specific databases

    HPAiHPA031652.

    Interactioni

    Subunit structurei

    Interacts with WNK1 and WNK4.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP3P425742EBI-1182602,EBI-524064

    Protein-protein interaction databases

    BioGridi122422. 4 interactions.
    IntActiQ9BYP7. 2 interactions.
    STRINGi9606.ENSP00000346667.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9BYP7.
    SMRiQ9BYP7. Positions 136-498.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini147 – 405259Protein 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.
    HOGENOMiHOG000049042.
    HOVERGENiHBG050346.
    KOiK08867.
    OMAiERRDSQC.
    PhylomeDBiQ9BYP7.
    TreeFamiTF315363.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR024678. Kinase_OSR1/WNK_CCT.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF12202. OSR1_C. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9BYP7-1) [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

    MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG     50
    ETVERKRFFR KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG 100
    GQEVKYEQCS KSTSEISKDC FKEKNEKEME EEAEMKAVAT SPSGRFLKFD 150
    IELGRGAFKT VYKGLDTETW VEVAWCELQD RKLTKAEQQR FKEEAEMLKG 200
    LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK RFKVMKPKVL 250
    RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL 300
    MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE 350
    CQNAAQIYRK VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL 400
    NHAFFAEDTG LRVELAEEDD CSNSSLALRL WVEDPKKLKG KHKDNEAIEF 450
    SFNLETDTPE EVAYEMVKSG FFHESDSKAV AKSIRDRVTP IKKTREKKPA 500
    GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE TEVDQHVRQQ 550
    LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV 600
    SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST 650
    VLPVHVLGPT VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR 700
    SLNQDVATTK ENVSSPDNPS GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ 750
    VSTSGDNMVE CQLETHNNKM VTFKFDVDGD APEDIADYMV EDNFVLESEK 800
    EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS QTGSSEQVQI 850
    NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR 900
    HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA 950
    SVETKQPAIL YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI 1000
    FIPVYPCHQT ASQADALMSH PGESTQTSGN SLTTLAFDQK PQTLSVQQPA 1050
    MDAEFISQEG ETTVNTEASS PKTVIPTQTP GLEPTTLQPT TVLESDGERP 1100
    PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS IDSPFSSSAE 1150
    DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF 1200
    KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGGGY 1250
    FGLSFTCPSL KNPISKKSWT RKLKSWAYRL RQSTSFFKRS KVRQVETEEM 1300
    RSAIAPDPIP LTRESTADTR ALNRCKAMSG SFQRGRFQVI TIPQQQSAKM 1350
    TSFGIEHISV FSETNHSSEE AFIKTAKSQL VEIEPATQNP KTSFSYEKLQ 1400
    ALQETCKENK GVPKQGDNFL SFSAACETDV SSVTPEKEFE ETSATGSSMQ 1450
    SGSELLLKER EILTAGKQPS SDSEFSASLA GSGKSVAKTG PESNQCLPHH 1500
    EEQAYAQTQS SLFYSPSSPM SSDDESEIED EDLKVELQRL REKHIQEVVN 1550
    LQTQQNKELQ ELYERLRSIK DSKTQSTEIP LPPASPRRPR SFKSKLRSRP 1600
    QSLTHVDNGI VATGKSCLIN ELENPLCVES NAASCQQSPA SKKGMFTDDL 1650
    HKLVDDWTKE AVGNSLIKPS LNQLKQSQHK LETENWNKVS ENTPSTMGYT 1700
    STWISSLSQI RGAVPTSLPQ GLSLPSFPGP LSSYGMPHVC QYNAVAGAGY 1750
    PVQWVGISGT TQQSVVIPAQ SGGPFQPGMN MQAFPTSSVQ NPATIPPGPK 1800
    Length:1,800
    Mass (Da):198,416
    Last modified:October 19, 2011 - v3
    Checksum:i1766D6AC8C7DE864
    GO
    Isoform 2 (identifier: Q9BYP7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1614-1624: GKSCLINELEN → D

    Note: No experimental confirmation available.

    Show »
    Length:1,790
    Mass (Da):197,329
    Checksum:iF49E2D171D308FE3
    GO
    Isoform 3 (identifier: Q9BYP7-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1248-1294: Missing.
         1614-1624: GKSCLINELEN → D

    Show »
    Length:1,743
    Mass (Da):191,789
    Checksum:i7B06CC8C7E8E4D67
    GO
    Isoform 4 (identifier: Q9BYP7-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1248-1294: Missing.

    Show »
    Length:1,753
    Mass (Da):192,875
    Checksum:iD08B93F28F01E049
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti10 – 101S → N in AAL99253. (PubMed:15194194)Curated
    Sequence conflicti431 – 4322WV → RD in BAB13392. (PubMed:10997877)Curated
    Sequence conflicti1211 – 12111P → S in BAB13392. (PubMed:10997877)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti704 – 7041Q → H.1 Publication
    Corresponds to variant rs56077971 [ dbSNP | Ensembl ].
    VAR_041323
    Natural varianti854 – 8541S → C in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041324
    Natural varianti998 – 9981A → T.1 Publication
    Corresponds to variant rs56404148 [ dbSNP | Ensembl ].
    VAR_041325
    Natural varianti1169 – 11691K → E.1 Publication
    Corresponds to variant rs55903619 [ dbSNP | Ensembl ].
    VAR_041326
    Natural varianti1375 – 13751T → I.1 Publication
    Corresponds to variant rs55879434 [ dbSNP | Ensembl ].
    VAR_041327
    Natural varianti1533 – 15331L → F in a lung large cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041328
    Natural varianti1634 – 16341S → P in a renal clear cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041329

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1248 – 129447Missing in isoform 3 and isoform 4. 2 PublicationsVSP_041932Add
    BLAST
    Alternative sequencei1614 – 162411GKSCLINELEN → D in isoform 3 and isoform 2. 2 PublicationsVSP_041933Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ409088 mRNA. Translation: CAC32455.2.
    AY082340 mRNA. Translation: AAL99253.1.
    AY352048 mRNA. Translation: AAR89465.1.
    AL591766, AL049793, Z84469 Genomic DNA. Translation: CAI40707.1.
    Z84469, AL049793, AL591766 Genomic DNA. Translation: CAI42732.1.
    AL049793, AL591766, Z84469 Genomic DNA. Translation: CAI43128.1.
    AL591766, AL049793, Z84469 Genomic DNA. Translation: CAI40708.1.
    Z84469, AL049793, AL591766 Genomic DNA. Translation: CAI42733.1.
    AL049793, AL591766, Z84469 Genomic DNA. Translation: CAI43129.1.
    AB046786 mRNA. Translation: BAB13392.1.
    CCDSiCCDS14357.1. [Q9BYP7-1]
    CCDS35302.1. [Q9BYP7-3]
    RefSeqiNP_001002838.1. NM_001002838.3. [Q9BYP7-3]
    NP_065973.2. NM_020922.4. [Q9BYP7-1]
    XP_006724656.1. XM_006724593.1. [Q9BYP7-3]
    XP_006724657.1. XM_006724594.1. [Q9BYP7-3]
    UniGeneiHs.92423.

    Genome annotation databases

    EnsembliENST00000354646; ENSP00000346667; ENSG00000196632. [Q9BYP7-1]
    ENST00000375159; ENSP00000364301; ENSG00000196632. [Q9BYP7-1]
    ENST00000375169; ENSP00000364312; ENSG00000196632. [Q9BYP7-3]
    GeneIDi65267.
    KEGGihsa:65267.
    UCSCiuc004dtc.2. human. [Q9BYP7-1]
    uc004dtd.2. human. [Q9BYP7-3]

    Polymorphism databases

    DMDMi353526307.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ409088 mRNA. Translation: CAC32455.2 .
    AY082340 mRNA. Translation: AAL99253.1 .
    AY352048 mRNA. Translation: AAR89465.1 .
    AL591766 , AL049793 , Z84469 Genomic DNA. Translation: CAI40707.1 .
    Z84469 , AL049793 , AL591766 Genomic DNA. Translation: CAI42732.1 .
    AL049793 , AL591766 , Z84469 Genomic DNA. Translation: CAI43128.1 .
    AL591766 , AL049793 , Z84469 Genomic DNA. Translation: CAI40708.1 .
    Z84469 , AL049793 , AL591766 Genomic DNA. Translation: CAI42733.1 .
    AL049793 , AL591766 , Z84469 Genomic DNA. Translation: CAI43129.1 .
    AB046786 mRNA. Translation: BAB13392.1 .
    CCDSi CCDS14357.1. [Q9BYP7-1 ]
    CCDS35302.1. [Q9BYP7-3 ]
    RefSeqi NP_001002838.1. NM_001002838.3. [Q9BYP7-3 ]
    NP_065973.2. NM_020922.4. [Q9BYP7-1 ]
    XP_006724656.1. XM_006724593.1. [Q9BYP7-3 ]
    XP_006724657.1. XM_006724594.1. [Q9BYP7-3 ]
    UniGenei Hs.92423.

    3D structure databases

    ProteinModelPortali Q9BYP7.
    SMRi Q9BYP7. Positions 136-498.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 122422. 4 interactions.
    IntActi Q9BYP7. 2 interactions.
    STRINGi 9606.ENSP00000346667.

    Chemistry

    ChEMBLi CHEMBL6055.
    GuidetoPHARMACOLOGYi 2282.

    PTM databases

    PhosphoSitei Q9BYP7.

    Polymorphism databases

    DMDMi 353526307.

    Proteomic databases

    MaxQBi Q9BYP7.
    PaxDbi Q9BYP7.
    PRIDEi Q9BYP7.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000354646 ; ENSP00000346667 ; ENSG00000196632 . [Q9BYP7-1 ]
    ENST00000375159 ; ENSP00000364301 ; ENSG00000196632 . [Q9BYP7-1 ]
    ENST00000375169 ; ENSP00000364312 ; ENSG00000196632 . [Q9BYP7-3 ]
    GeneIDi 65267.
    KEGGi hsa:65267.
    UCSCi uc004dtc.2. human. [Q9BYP7-1 ]
    uc004dtd.2. human. [Q9BYP7-3 ]

    Organism-specific databases

    CTDi 65267.
    GeneCardsi GC0XM054235.
    HGNCi HGNC:14543. WNK3.
    HPAi HPA031652.
    MIMi 300358. gene.
    neXtProti NX_Q9BYP7.
    PharmGKBi PA33784.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000049042.
    HOVERGENi HBG050346.
    KOi K08867.
    OMAi ERRDSQC.
    PhylomeDBi Q9BYP7.
    TreeFami TF315363.

    Enzyme and pathway databases

    Reactomei REACT_160189. Stimuli-sensing channels.
    SignaLinki Q9BYP7.

    Miscellaneous databases

    GeneWikii WNK3.
    GenomeRNAii 65267.
    NextBioi 67402.
    PROi Q9BYP7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9BYP7.
    Bgeei Q9BYP7.
    CleanExi HS_WNK3.
    Genevestigatori Q9BYP7.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR024678. Kinase_OSR1/WNK_CCT.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF12202. OSR1_C. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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] (ISOFORM 3), TISSUE SPECIFICITY, CHROMOSOMAL LOCATION.
      Tissue: Brain1 Publication.
    2. Jordan P.
      Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO N-TERMINUS.
    3. "Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3)."
      Holden S., Cox J., Raymond F.L.
      Gene 335:109-119(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
      Tissue: Brain.
    4. "The DNA sequence of the human X chromosome."
      Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.
      , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
      Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.
      DNA Res. 7:273-281(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-1800 (ISOFORM 3).
      Tissue: Brain1 Publication.
    6. "WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis."
      Rinehart J., Kahle K.T., de Los Heros P., Vazquez N., Meade P., Wilson F.H., Hebert S.C., Gimenez I., Gamba G., Lifton R.P.
      Proc. Natl. Acad. Sci. U.S.A. 102:16777-16782(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-294, TISSUE SPECIFICITY.
    7. "WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability."
      Kahle K.T., Rinehart J., de Los Heros P., Louvi A., Meade P., Vazquez N., Hebert S.C., Gamba G., Gimenez I., Lifton R.P.
      Proc. Natl. Acad. Sci. U.S.A. 102:16783-16788(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)."
      Leng Q., Kahle K.T., Rinehart J., MacGregor G.G., Wilson F.H., Canessa C.M., Lifton R.P., Hebert S.C.
      J. Physiol. (Lond.) 571:275-286(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway."
      Verissimo F., Silva E., Morris J.D., Pepperkok R., Jordan P.
      Oncogene 25:4172-4182(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    10. "The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex."
      Yang C.L., Zhu X., Ellison D.H.
      J. Clin. Invest. 117:3403-3411(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH WNK1 AND WNK4, ENZYME REGULATION.
    11. "WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway."
      Zhang W., Na T., Peng J.B.
      Am. J. Physiol. 295:F1472-F1484(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "Renal and brain isoforms of WNK3 have opposite effects on NCCT expression."
      Glover M., Zuber A.M., O'Shaughnessy K.M.
      J. Am. Soc. Nephrol. 20:1314-1322(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ALTERNATIVE SPLICING.
    14. "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.
    15. Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORM 4), MUTAGENESIS OF ASP-294.
    16. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    17. Cited for: UBIQUITINATION BY KLHL2.
    18. "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] HIS-704; CYS-854; THR-998; GLU-1169; ILE-1375; PHE-1533 AND PRO-1634.

    Entry informationi

    Entry nameiWNK3_HUMAN
    AccessioniPrimary (citable) accession number: Q9BYP7
    Secondary accession number(s): B1AKG2
    , Q5JRC1, Q6JP76, Q8TCX6, Q9HCK6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 2, 2004
    Last sequence update: October 19, 2011
    Last modified: October 1, 2014
    This is version 127 of the entry and version 3 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome X
      Human chromosome X: 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. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3