Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q7TPK6 (WNK4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Wnk4
Synonyms:Prkwnk4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1222 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9H4A3

Cofactor

Magnesium By similarity. UniProtKB Q9H4A3

Enzyme regulation

Activation requires autophosphorylation of Ser-332. Phosphorylation of Ser-328 also promotes increased activity By similarity. UniProtKB Q9JIH7

Subunit structure

Interacts with the C-terminal region of KCNJ1 By similarity. Interacts with KLHL3, WNK1 and WNK3 By similarity. UniProtKB Q80UE6

Subcellular location

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.

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.

Contains 1 protein kinase domain.

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.

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12221222Serine/threonine-protein kinase WNK4
PRO_0000086826

Regions

Domain171 – 429259Protein kinase
Nucleotide binding177 – 1859ATP By similarity

Sites

Active site2991Proton acceptor By similarity
Binding site1831ATP By similarity

Amino acid modifications

Modified residue3281Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
Modified residue3321Phosphoserine; by autocatalysis By similarity UniProtKB Q9JIH7
Cross-link154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link183Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link223Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link390Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link447Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link990Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link1123Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link1136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link1137Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Sequence conflict91T → R in AAO18238. Ref.1
Sequence conflict2041T → A in AAO18238. Ref.1
Sequence conflict7641P → A in AAO18238. Ref.1
Sequence conflict7761A → E in AAO18238. Ref.1
Sequence conflict11941R → K in AAO18238. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q7TPK6 [UniParc].

Last modified August 30, 2005. Version 3.
Checksum: E7E53DAC9D1FA446

FASTA1,222132,833
        10         20         30         40         50         60 
MLAPRNTETG VHMSQTEADL ALRPSPSLTS MGPTRLGPPP RRVRRFSGKA EPRPRSSRPS 

        70         80         90        100        110        120 
RRSSVDLGLL SSWSQPASLL PEPPDPPDSA GPMRSPPSNS KEHPEGTWTG AAPVKAADSA 

       130        140        150        160        170        180 
CPELTVSSGG PGSREPPRVP DAAARERRRE QEEKEDTETQ AVATSPDGRY LKFDIEIGRG 

       190        200        210        220        230        240 
SFKTVYRGLD TDTTVEVAWC ELQTRKLSRA ERQRFSEEVE MLKGLQHPNI VRFYDSWKSV 

       250        260        270        280        290        300 
LRGQVCIVLV TELMTSGTLK TYLRRFREMK PRVLQRWSRQ ILRGLHFLHS RVPPILHRDL 

       310        320        330        340        350        360 
KCDNVFITGP SGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD EAVDVYAFGM 

       370        380        390        400        410        420 
CMLEMATSEY PYSECQNAAQ IYRKVTSGTK PNSFYKVKMP EVKEIIEGCI RTDKNERFTI 

       430        440        450        460        470        480 
QDLLTHAFFR EERGVHVELA EEDDGEKPGL KLWLRMEDAR RGGRPRDNQA IEFLFQLGRD 

       490        500        510        520        530        540 
AAEEVAQEMV ALGLVCEADY QPVARAVRER VAAIQRKREK LRKARELEVL PPDSGPPPAT 

       550        560        570        580        590        600 
VSMTPGPPSA FPPEPEEPEA DQHQSFLFRH ASYSSTTSDC ETDGYLSSSG FLDASDPALQ 

       610        620        630        640        650        660 
PPGGMPSSPA EPHLCLPSGF ALSIPRSGPG SDFSPGDSYA SDAASGLSDM GEGGQMRKNP 

       670        680        690        700        710        720 
VKTLRRRPRS RLRVTSVSDQ SDRVVECQLQ THNSKMVTFR FDLDGDSPEE IAAAMVYNEF 

       730        740        750        760        770        780 
ILPSERDGFL SRIREIIQRV ETLLKRDAGP SEATEDALSP QEEPAAMPAL PGPSDAELQR 

       790        800        810        820        830        840 
SISPEQRSWA AFSTSPSSPG TPLSPGTPFS PGTPPVFPCP IFPITSPSCH PYPFSQVSSN 

       850        860        870        880        890        900 
PCPQAPSSLL PSSSGASQVP FPSPSLPTSS PLPFSPSYPQ VPLHPASLPT CPSPPPLPST 

       910        920        930        940        950        960 
TAAPLLSLAS AFSLAVMTVA QSLLSPSPGL LSQSPPAPPG PLPSMPLPLA SCDQESLSAQ 

       970        980        990       1000       1010       1020 
TAETENEASR NPAQPLLGDA RLAPISEEGK PQLVGRFQVT SSKEPAEPPL QPASPTLSRS 

      1030       1040       1050       1060       1070       1080 
LKLPTPQLTS ESSDTEDSAA GGPETREALA ESDRAAEGLG VAIDEEKDEG KEPQIGGSSP 

      1090       1100       1110       1120       1130       1140 
ILSQPSPVWM NYSYSSLCLS SEESESSGED EEFWAELQNL RQKHLSEVEA LQTLQKKEIE 

      1150       1160       1170       1180       1190       1200 
DLYSRLGKQP PPGIVAPAAM LSCRQRRLSK GSFPTSRRNS LQRSDLPGPG IMRRNSLSGS 

      1210       1220 
STGSQEQRAS KGVTFAGDVG RM 

« Hide

References

[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 Kyoto.
Tissue: Kidney.
[2]"WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion."
Kahle K.T., Wilson F.H., Leng Q., Lalioti M.D., O'Connell A.D., Dong K., Rapson A.K., MacGregor G.G., Giebisch G., Hebert S.C., Lifton R.P.
Nat. Genet. 35:372-376(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar Kyoto.
Tissue: Kidney.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY187039 mRNA. Translation: AAO18238.1. Frameshift.
AY192567 mRNA. Translation: AAO38858.1.
RefSeqNP_783169.2. NM_175579.3.
UniGeneRn.228251.

3D structure databases

ProteinModelPortalQ7TPK6.
SMRQ7TPK6. Positions 161-430.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59689N.

PTM databases

PhosphoSiteQ7TPK6.

Proteomic databases

PRIDEQ7TPK6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000027770; ENSRNOP00000027770; ENSRNOG00000020441.
GeneID287715.
KEGGrno:287715.
UCSCRGD:631401. rat.

Organism-specific databases

CTD65266.
RGD631401. Wnk4.

Phylogenomic databases

GeneTreeENSGT00550000074385.
HOGENOMHOG000230962.
HOVERGENHBG050347.
InParanoidQ7TPK6.
KOK08867.
OMAESHLRLP.
PhylomeDBQ7TPK6.
TreeFamTF315363.

Gene expression databases

GenevestigatorQ7TPK6.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio626859.
PROQ7TPK6.

Entry information

Entry nameWNK4_RAT
AccessionPrimary (citable) accession number: Q7TPK6
Secondary accession number(s): Q810H4, Q811R5
Entry history
Integrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: August 30, 2005
Last modified: July 9, 2014
This is version 105 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families