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Q7TPK6

- WNK4_RAT

UniProt

Q7TPK6 - WNK4_RAT

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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

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 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
Complete GO annotation...

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
Complete GO annotation...

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

ExpressionAtlasiQ7TPK6. baseline.
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 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLAPRNTETG VHMSQTEADL ALRPSPSLTS MGPTRLGPPP RRVRRFSGKA
60 70 80 90 100
EPRPRSSRPS RRSSVDLGLL SSWSQPASLL PEPPDPPDSA GPMRSPPSNS
110 120 130 140 150
KEHPEGTWTG AAPVKAADSA CPELTVSSGG PGSREPPRVP DAAARERRRE
160 170 180 190 200
QEEKEDTETQ AVATSPDGRY LKFDIEIGRG SFKTVYRGLD TDTTVEVAWC
210 220 230 240 250
ELQTRKLSRA ERQRFSEEVE MLKGLQHPNI VRFYDSWKSV LRGQVCIVLV
260 270 280 290 300
TELMTSGTLK TYLRRFREMK PRVLQRWSRQ ILRGLHFLHS RVPPILHRDL
310 320 330 340 350
KCDNVFITGP SGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD
360 370 380 390 400
EAVDVYAFGM CMLEMATSEY PYSECQNAAQ IYRKVTSGTK PNSFYKVKMP
410 420 430 440 450
EVKEIIEGCI RTDKNERFTI QDLLTHAFFR EERGVHVELA EEDDGEKPGL
460 470 480 490 500
KLWLRMEDAR RGGRPRDNQA IEFLFQLGRD AAEEVAQEMV ALGLVCEADY
510 520 530 540 550
QPVARAVRER VAAIQRKREK LRKARELEVL PPDSGPPPAT VSMTPGPPSA
560 570 580 590 600
FPPEPEEPEA DQHQSFLFRH ASYSSTTSDC ETDGYLSSSG FLDASDPALQ
610 620 630 640 650
PPGGMPSSPA EPHLCLPSGF ALSIPRSGPG SDFSPGDSYA SDAASGLSDM
660 670 680 690 700
GEGGQMRKNP VKTLRRRPRS RLRVTSVSDQ SDRVVECQLQ THNSKMVTFR
710 720 730 740 750
FDLDGDSPEE IAAAMVYNEF ILPSERDGFL SRIREIIQRV ETLLKRDAGP
760 770 780 790 800
SEATEDALSP QEEPAAMPAL PGPSDAELQR SISPEQRSWA AFSTSPSSPG
810 820 830 840 850
TPLSPGTPFS PGTPPVFPCP IFPITSPSCH PYPFSQVSSN PCPQAPSSLL
860 870 880 890 900
PSSSGASQVP FPSPSLPTSS PLPFSPSYPQ VPLHPASLPT CPSPPPLPST
910 920 930 940 950
TAAPLLSLAS AFSLAVMTVA QSLLSPSPGL LSQSPPAPPG PLPSMPLPLA
960 970 980 990 1000
SCDQESLSAQ TAETENEASR NPAQPLLGDA RLAPISEEGK PQLVGRFQVT
1010 1020 1030 1040 1050
SSKEPAEPPL QPASPTLSRS LKLPTPQLTS ESSDTEDSAA GGPETREALA
1060 1070 1080 1090 1100
ESDRAAEGLG VAIDEEKDEG KEPQIGGSSP ILSQPSPVWM NYSYSSLCLS
1110 1120 1130 1140 1150
SEESESSGED EEFWAELQNL RQKHLSEVEA LQTLQKKEIE DLYSRLGKQP
1160 1170 1180 1190 1200
PPGIVAPAAM LSCRQRRLSK GSFPTSRRNS LQRSDLPGPG IMRRNSLSGS
1210 1220
STGSQEQRAS KGVTFAGDVG RM
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

ExpressionAtlasi Q7TPK6. baseline.
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 29, 2014
This is version 108 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