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Q7TPK6

- WNK4_RAT

UniProt

Q7TPK6 - WNK4_RAT

Protein

Serine/threonine-protein kinase WNK4

Gene

Wnk4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 3 (30 Aug 2005)
      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 By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme regulationi

    Activation requires autophosphorylation of Ser-332. Phosphorylation of Ser-328 also promotes increased activity By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei183 – 1831ATPPROSITE-ProRule annotation
    Active sitei299 – 2991Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi177 – 1859ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. distal tubule morphogenesis Source: UniProtKB
    2. intracellular signal transduction Source: UniProtKB
    3. ion homeostasis Source: UniProtKB
    4. ion transport Source: UniProtKB
    5. protein phosphorylation Source: UniProtKB
    6. regulation of cellular process Source: UniProtKB
    7. 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_198302. Stimuli-sensing channels.

    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:Prkwnk4By similarity
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi631401. 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. tight junction Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Tight junction

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12221222Serine/threonine-protein kinase WNK4PRO_0000086826Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki154 – 154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki172 – 172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki183 – 183Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki223 – 223Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki238 – 238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki325 – 325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei328 – 3281Phosphoserine; by autocatalysisBy similarity
    Modified residuei332 – 3321Phosphoserine; by autocatalysisBy similarity
    Cross-linki384 – 384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki390 – 390Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki447 – 447Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki451 – 451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki990 – 990Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki1123 – 1123Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki1136 – 1136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Cross-linki1137 – 1137Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    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 By similarity.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiQ7TPK6.

    PTM databases

    PhosphoSiteiQ7TPK6.

    Expressioni

    Gene expression databases

    GenevestigatoriQ7TPK6.

    Interactioni

    Subunit structurei

    Interacts with the C-terminal region of KCNJ1. Interacts with KLHL3, WNK1 and WNK3.By similarity

    Protein-protein interaction databases

    DIPiDIP-59689N.

    Structurei

    3D structure databases

    ProteinModelPortaliQ7TPK6.
    SMRiQ7TPK6. Positions 161-430.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini171 – 429259Protein 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

    GeneTreeiENSGT00550000074385.
    HOGENOMiHOG000230962.
    HOVERGENiHBG050347.
    InParanoidiQ7TPK6.
    KOiK08867.
    OMAiESHLRLP.
    PhylomeDBiQ7TPK6.
    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]

    Sequencei

    Sequence statusi: Complete.

    Q7TPK6-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLAPRNTETG VHMSQTEADL ALRPSPSLTS MGPTRLGPPP RRVRRFSGKA     50
    EPRPRSSRPS RRSSVDLGLL SSWSQPASLL PEPPDPPDSA GPMRSPPSNS 100
    KEHPEGTWTG AAPVKAADSA CPELTVSSGG PGSREPPRVP DAAARERRRE 150
    QEEKEDTETQ AVATSPDGRY LKFDIEIGRG SFKTVYRGLD TDTTVEVAWC 200
    ELQTRKLSRA ERQRFSEEVE MLKGLQHPNI VRFYDSWKSV LRGQVCIVLV 250
    TELMTSGTLK TYLRRFREMK PRVLQRWSRQ ILRGLHFLHS RVPPILHRDL 300
    KCDNVFITGP SGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD 350
    EAVDVYAFGM CMLEMATSEY PYSECQNAAQ IYRKVTSGTK PNSFYKVKMP 400
    EVKEIIEGCI RTDKNERFTI QDLLTHAFFR EERGVHVELA EEDDGEKPGL 450
    KLWLRMEDAR RGGRPRDNQA IEFLFQLGRD AAEEVAQEMV ALGLVCEADY 500
    QPVARAVRER VAAIQRKREK LRKARELEVL PPDSGPPPAT VSMTPGPPSA 550
    FPPEPEEPEA DQHQSFLFRH ASYSSTTSDC ETDGYLSSSG FLDASDPALQ 600
    PPGGMPSSPA EPHLCLPSGF ALSIPRSGPG SDFSPGDSYA SDAASGLSDM 650
    GEGGQMRKNP VKTLRRRPRS RLRVTSVSDQ SDRVVECQLQ THNSKMVTFR 700
    FDLDGDSPEE IAAAMVYNEF ILPSERDGFL SRIREIIQRV ETLLKRDAGP 750
    SEATEDALSP QEEPAAMPAL PGPSDAELQR SISPEQRSWA AFSTSPSSPG 800
    TPLSPGTPFS PGTPPVFPCP IFPITSPSCH PYPFSQVSSN PCPQAPSSLL 850
    PSSSGASQVP FPSPSLPTSS PLPFSPSYPQ VPLHPASLPT CPSPPPLPST 900
    TAAPLLSLAS AFSLAVMTVA QSLLSPSPGL LSQSPPAPPG PLPSMPLPLA 950
    SCDQESLSAQ TAETENEASR NPAQPLLGDA RLAPISEEGK PQLVGRFQVT 1000
    SSKEPAEPPL QPASPTLSRS LKLPTPQLTS ESSDTEDSAA GGPETREALA 1050
    ESDRAAEGLG VAIDEEKDEG KEPQIGGSSP ILSQPSPVWM NYSYSSLCLS 1100
    SEESESSGED EEFWAELQNL RQKHLSEVEA LQTLQKKEIE DLYSRLGKQP 1150
    PPGIVAPAAM LSCRQRRLSK GSFPTSRRNS LQRSDLPGPG IMRRNSLSGS 1200
    STGSQEQRAS KGVTFAGDVG RM 1222
    Length:1,222
    Mass (Da):132,833
    Last modified:August 30, 2005 - v3
    Checksum:iE7E53DAC9D1FA446
    GO

    Sequence cautioni

    The sequence AAO18238.1 differs from that shown. Reason: Frameshift at position 170.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti9 – 91T → R in AAO18238. (PubMed:12642508)Curated
    Sequence conflicti204 – 2041T → A in AAO18238. (PubMed:12642508)Curated
    Sequence conflicti764 – 7641P → A in AAO18238. (PubMed:12642508)Curated
    Sequence conflicti776 – 7761A → E in AAO18238. (PubMed:12642508)Curated
    Sequence conflicti1194 – 11941R → K in AAO18238. (PubMed:12642508)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY187039 mRNA. Translation: AAO18238.1. Frameshift.
    AY192567 mRNA. Translation: AAO38858.1.
    RefSeqiNP_783169.2. NM_175579.3.
    UniGeneiRn.228251.

    Genome annotation databases

    EnsembliENSRNOT00000027770; ENSRNOP00000027770; ENSRNOG00000020441.
    GeneIDi287715.
    KEGGirno:287715.
    UCSCiRGD:631401. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY187039 mRNA. Translation: AAO18238.1 . Frameshift.
    AY192567 mRNA. Translation: AAO38858.1 .
    RefSeqi NP_783169.2. NM_175579.3.
    UniGenei Rn.228251.

    3D structure databases

    ProteinModelPortali Q7TPK6.
    SMRi Q7TPK6. Positions 161-430.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-59689N.

    PTM databases

    PhosphoSitei Q7TPK6.

    Proteomic databases

    PRIDEi Q7TPK6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000027770 ; ENSRNOP00000027770 ; ENSRNOG00000020441 .
    GeneIDi 287715.
    KEGGi rno:287715.
    UCSCi RGD:631401. rat.

    Organism-specific databases

    CTDi 65266.
    RGDi 631401. Wnk4.

    Phylogenomic databases

    GeneTreei ENSGT00550000074385.
    HOGENOMi HOG000230962.
    HOVERGENi HBG050347.
    InParanoidi Q7TPK6.
    KOi K08867.
    OMAi ESHLRLP.
    PhylomeDBi Q7TPK6.
    TreeFami TF315363.

    Enzyme and pathway databases

    Reactomei REACT_198302. Stimuli-sensing channels.

    Miscellaneous databases

    NextBioi 626859.
    PROi Q7TPK6.

    Gene expression databases

    Genevestigatori Q7TPK6.

    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. "The role of Wnk4 in polygenic hypertension: a candidate gene analysis on rat chromosome 10."
      Monti J., Zimdahl H., Schulz H., Plehm R., Ganten D., Hubner N.
      Hypertension 41:938-942(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar Kyoto1 Publication.
      Tissue: KidneyImported.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar Kyoto1 Publication.
      Tissue: KidneyImported.

    Entry informationi

    Entry nameiWNK4_RAT
    AccessioniPrimary (citable) accession number: Q7TPK6
    Secondary accession number(s): Q810H4, Q811R5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 2, 2004
    Last sequence update: August 30, 2005
    Last modified: October 1, 2014
    This is version 107 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Cys-200 is present instead of the conserved Lys which is expected to be an active site residue. Lys-183 appears to fulfill the required catalytic function.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3