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Protein

Serine/threonine-protein kinase WNK4

Gene

Wnk4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition. Phosphorylates NEDD4L (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+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)DescriptionActionsGraphical viewLength
Binding sitei181ATP; via amide nitrogenBy similarity1
Binding sitei301ATPBy similarity1
Active sitei318Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi251 – 254ATPBy similarity4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-2672351. Stimuli-sensing channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK4Curated (EC:2.7.11.1By similarity)
Alternative name(s):
Protein kinase lysine-deficient 4Imported
Protein kinase with no lysine 4Curated
Gene namesi
Name:Wnk4Imported
Synonyms:Prkwnk41 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi631401. Wnk4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Tight junction

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868261 – 1222Serine/threonine-protein kinase WNK4Add BLAST1222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei95PhosphoserineBy similarity1
Cross-linki154Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki172Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki183Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki223Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei328Phosphoserine; by autocatalysisBy similarity1
Modified residuei332Phosphoserine; by autocatalysisBy similarity1
Cross-linki384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki390Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki447Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki451Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki990Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei1014PhosphoserineCombined sources1
Cross-linki1123Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1136Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki1137Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei1196PhosphoserineBy similarity1

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

PaxDbiQ7TPK6.
PRIDEiQ7TPK6.

PTM databases

iPTMnetiQ7TPK6.
PhosphoSitePlusiQ7TPK6.

Expressioni

Gene expression databases

BgeeiENSRNOG00000020441.
ExpressionAtlasiQ7TPK6. baseline.
GenevisibleiQ7TPK6. RN.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

DIPiDIP-59689N.
STRINGi10116.ENSRNOP00000027804.

Structurei

3D structure databases

ProteinModelPortaliQ7TPK6.
SMRiQ7TPK6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini171 – 429Protein kinasePROSITE-ProRule annotationAdd BLAST259

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0584. Eukaryota.
KOG4068. Eukaryota.
ENOG410XQWZ. LUCA.
GeneTreeiENSGT00800000124049.
HOGENOMiHOG000230962.
HOVERGENiHBG050347.
InParanoidiQ7TPK6.
KOiK08867.
OMAiWAELQNL.
OrthoDBiEOG091G06LL.
PhylomeDBiQ7TPK6.
TreeFamiTF315363.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR024678. Kinase_OSR1/WNK_CCT.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF12202. OSR1_C. 1 hit.
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiView protein in PROSITE
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Q7TPK6-1 [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 differs from that shown. Reason: Frameshift at position 170.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9T → R in AAO18238 (PubMed:12642508).Curated1
Sequence conflicti204T → A in AAO18238 (PubMed:12642508).Curated1
Sequence conflicti764P → A in AAO18238 (PubMed:12642508).Curated1
Sequence conflicti776A → E in AAO18238 (PubMed:12642508).Curated1
Sequence conflicti1194R → K in AAO18238 (PubMed:12642508).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Similar proteinsi

Entry informationi

Entry nameiWNK4_RAT
AccessioniPrimary (citable) accession number: Q7TPK6
Secondary accession number(s): Q810H4, Q811R5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: August 30, 2005
Last modified: August 30, 2017
This is version 131 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins.By similarity

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families