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Q80XP9

- WNK3_MOUSE

UniProt

Q80XP9 - WNK3_MOUSE

Protein

Serine/threonine-protein kinase WNK3

Gene

Wnk3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 82 (01 Oct 2014)
      Sequence version 3 (09 Jan 2013)
      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 SLC12A1, SLC12A2, SLC12A3, SCNN1A, SCNN1B, SCNN1D and SGK1. Inhibits SLC12A4, SLC12A5, SLC12A6 and SLC12A7. Phosphorylates WNK4. Increases Ca2+ influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway. Inhibits KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.1 Publication

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activation requires autophosphorylation of Ser-307. Phosphorylation of Ser-303 also promotes increased activity. Kinase activity is inhibited by WNK4 By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei158 – 1581ATPPROSITE-ProRule annotation
    Active sitei274 – 2741Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi152 – 1609ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein kinase activity Source: UniProtKB
    3. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. positive regulation of establishment of protein localization to plasma membrane Source: UniProtKB
    2. positive regulation of ion transmembrane transporter activity Source: UniProtKB
    3. positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    4. positive regulation of rubidium ion transmembrane transporter activity Source: UniProtKB
    5. positive regulation of rubidium ion transport Source: UniProtKB
    6. positive regulation of sodium ion transmembrane transporter activity Source: UniProtKB
    7. positive regulation of sodium ion transport Source: UniProtKB
    8. protein autophosphorylation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:2652875. Wnk3.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 17571757Serine/threonine-protein kinase WNK3PRO_0000278775Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei62 – 621PhosphoserineBy similarity
    Modified residuei303 – 3031Phosphoserine; by autocatalysisBy similarity
    Modified residuei307 – 3071Phosphoserine; by autocatalysisBy similarity

    Post-translational modificationi

    Ubiquitinated by the BCR(KLHL2) complex, leading to its degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ80XP9.
    PRIDEiQ80XP9.

    PTM databases

    PhosphoSiteiQ80XP9.

    Expressioni

    Gene expression databases

    CleanExiMM_WNK3.
    GenevestigatoriQ80XP9.

    Interactioni

    Subunit structurei

    Interacts with WNK1 and WNK4.By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000094005.

    Structurei

    3D structure databases

    ProteinModelPortaliQ80XP9.
    SMRiQ80XP9. Positions 135-497.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini146 – 404259Protein 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.
    HOVERGENiHBG050346.
    InParanoidiQ80XP9.
    KOiK08867.

    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. 2 hits.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q80XP9-1) [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

    MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG     50
    ENIERKRFFR KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG 100
    QEVKYEQCSK ATSESSKDCF KEKTEKEMEE EAEMKAVATS PSGRFLKFDI 150
    ELGRGAFKTV YKGLDTETWV EVAWCELQDR KLTKAEQQRF KEEAEMLKGL 200
    QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR FKVMKPKVLR 250
    SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM 300
    RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC 350
    QNAAQIYRKV TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN 400
    HAFFAEDTGL RVELAEEDDC SNSSLALRLW VEDPKKLKGK HKDNEAIEFS 450
    FNLEADTPEE VAYEMVKSGF FHESDSKAVA KSIRDRVTLI KKIREKKPAG 500
    CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET EVDQHVRQQF 550
    LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP 600
    KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP 650
    IGAEQQATLQ NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS 700
    CPRPEKGTKF QLTVLQVSVS GDNMVECQLE THNNKMVTFK FDVDGDAPED 750
    IADYMVEDNF VLENEKEKFV EELRAIVGQA QEILHVHSAV EKSIGVDSVA 800
    LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC INQTIKNREA 850
    QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS 900
    KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV 950
    CPVPGECEAL TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT 1000
    SVLVSSDQKP QSLSVQQPTI DAEFISKEGE TTVNTETSSP KAVIATQTPG 1050
    FEPAVILPAT ILESDGERPP KMEFADNRIK TLDEKLRNLL YQEHSISSIC 1100
    PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS PAQSPNFQQT 1150
    GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA 1200
    YPAAVSSDGT IHLQTGGGYF GLSFTCPSLK NPISRKSWTR KLKSWAYRLR 1250
    QSTSFFKRSK VRQVETEDKR SAIASDPIPL TREFSSDTRA LSRCKAMSGS 1300
    FQRGRFQVIT VPQQQPVKMM SFGKDHRPPF NKTTVQSSEQ ALTFAEAAVS 1350
    QLIEVEPAMP THKASVSSRK LRTLYETFKE DKGDPEQGDI VSYSTACETS 1400
    VSSVATEKNV TSTTEVSVQS GSEPLDKEKN ESTPGKQTCT NEFSATLAGN 1450
    RKSVTKTRPE GDQYLPLREE QAYAQTQNSL FYSPSSPMSS DNESEIEDED 1500
    LKVELQRLRE KHIQEVVSLQ TQQNKELQEL YERLRATKDN KAQSSEVPLS 1550
    PASPRRPRSF KSKLRSRPQS MTHSDNLVVK DALGVESNTV SCQQSPASKK 1600
    GMFTDDLHKL VDDWTRETVG HFPSKPSLNQ LKQSQQKSEA ENWNKSCEST 1650
    PSTMGYTSNW ISSLSQIRGA APTSLPQGLP LPSFHGPLAS YGMPHVCQYN 1700
    AVGAAGYPVQ WVGISGPAQQ SVVLPTQSGG LFQPGMNLQS FPAPPVQNPA 1750
    SIPPGPK 1757
    Length:1,757
    Mass (Da):193,991
    Last modified:January 9, 2013 - v3
    Checksum:i3E5B070772BE6725
    GO
    Isoform 2 (identifier: Q80XP9-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1217-1263: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:1,710
    Mass (Da):188,423
    Checksum:iD825CA0153EC71F6
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1217 – 126347Missing in isoform 2. 1 PublicationVSP_041934Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    JQ247189 mRNA. Translation: AEZ01402.1.
    JQ247190 mRNA. Translation: AEZ01403.1.
    AL732420 Genomic DNA. No translation available.
    AL807396 Genomic DNA. No translation available.
    BC043119 mRNA. Translation: AAH43119.1.
    BC060731 mRNA. Translation: AAH60731.1.
    CCDSiCCDS72450.1. [Q80XP9-2]
    CCDS72451.1. [Q80XP9-1]
    RefSeqiNP_001258607.1. NM_001271678.1. [Q80XP9-1]
    NP_001258608.1. NM_001271679.1. [Q80XP9-2]
    XP_006528933.1. XM_006528870.1. [Q80XP9-1]
    XP_006528934.1. XM_006528871.1. [Q80XP9-1]
    XP_006528935.1. XM_006528872.1. [Q80XP9-1]
    XP_006528936.1. XM_006528873.1. [Q80XP9-1]
    XP_006528937.1. XM_006528874.1. [Q80XP9-2]
    UniGeneiMm.441474.

    Genome annotation databases

    EnsembliENSMUST00000184392; ENSMUSP00000139037; ENSMUSG00000041245. [Q80XP9-1]
    ENSMUST00000184730; ENSMUSP00000138822; ENSMUSG00000041245. [Q80XP9-2]
    GeneIDi279561.
    KEGGimmu:279561.
    UCSCiuc009upa.2. mouse. [Q80XP9-2]
    uc029xnn.1. mouse. [Q80XP9-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    JQ247189 mRNA. Translation: AEZ01402.1 .
    JQ247190 mRNA. Translation: AEZ01403.1 .
    AL732420 Genomic DNA. No translation available.
    AL807396 Genomic DNA. No translation available.
    BC043119 mRNA. Translation: AAH43119.1 .
    BC060731 mRNA. Translation: AAH60731.1 .
    CCDSi CCDS72450.1. [Q80XP9-2 ]
    CCDS72451.1. [Q80XP9-1 ]
    RefSeqi NP_001258607.1. NM_001271678.1. [Q80XP9-1 ]
    NP_001258608.1. NM_001271679.1. [Q80XP9-2 ]
    XP_006528933.1. XM_006528870.1. [Q80XP9-1 ]
    XP_006528934.1. XM_006528871.1. [Q80XP9-1 ]
    XP_006528935.1. XM_006528872.1. [Q80XP9-1 ]
    XP_006528936.1. XM_006528873.1. [Q80XP9-1 ]
    XP_006528937.1. XM_006528874.1. [Q80XP9-2 ]
    UniGenei Mm.441474.

    3D structure databases

    ProteinModelPortali Q80XP9.
    SMRi Q80XP9. Positions 135-497.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000094005.

    PTM databases

    PhosphoSitei Q80XP9.

    Proteomic databases

    PaxDbi Q80XP9.
    PRIDEi Q80XP9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000184392 ; ENSMUSP00000139037 ; ENSMUSG00000041245 . [Q80XP9-1 ]
    ENSMUST00000184730 ; ENSMUSP00000138822 ; ENSMUSG00000041245 . [Q80XP9-2 ]
    GeneIDi 279561.
    KEGGi mmu:279561.
    UCSCi uc009upa.2. mouse. [Q80XP9-2 ]
    uc029xnn.1. mouse. [Q80XP9-1 ]

    Organism-specific databases

    CTDi 65267.
    MGIi MGI:2652875. Wnk3.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00550000074385.
    HOVERGENi HBG050346.
    InParanoidi Q80XP9.
    KOi K08867.

    Miscellaneous databases

    NextBioi 35562242.
    PROi Q80XP9.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_WNK3.
    Genevestigatori Q80XP9.

    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. 2 hits.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Mouse Wnk3 gene encodes multiple continuous open reading frames."
      Shmukler B.E., Alper S.L.
      Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
      Strain: C57BL/6J.
      Tissue: Brain.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    3. "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] OF 1296-1757.
      Strain: C57BL/6.
      Tissue: Embryonic brain.
    4. "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.

    Entry informationi

    Entry nameiWNK3_MOUSE
    AccessioniPrimary (citable) accession number: Q80XP9
    Secondary accession number(s): H6WJI2, H6WJI3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 20, 2007
    Last sequence update: January 9, 2013
    Last modified: October 1, 2014
    This is version 82 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3