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Protein

Serine/threonine-protein kinase WNK4

Gene

Wnk4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

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

Catalytic activityi

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

Cofactori

Mg2+By similarity

Activity 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

  • ATP binding Source: UniProtKB
  • chloride channel inhibitor activity Source: GO_Central
  • potassium channel inhibitor activity Source: GO_Central
  • protein serine/threonine kinase activity Source: RGD

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 Expressed in 9 organ(s), highest expression level in adult mammalian kidney
ExpressionAtlasiQ7TPK6 baseline and differential
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
IntActiQ7TPK6, 1 interactor
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
OMAiLEHRSWA
OrthoDBiEOG091G06LL
PhylomeDBiQ7TPK6
TreeFamiTF315363

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
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, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2K231A0A0G2K231_RAT
Serine/threonine-protein kinase WNK...
Wnk4
1,034Annotation score:
A0A096MKH1A0A096MKH1_RAT
Serine/threonine-protein kinase WNK...
Wnk4
285Annotation score:

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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliQ7TPK6
SMRiQ7TPK6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59689N
IntActiQ7TPK6, 1 interactor
STRINGi10116.ENSRNOP00000027804

PTM databases

iPTMnetiQ7TPK6
PhosphoSitePlusiQ7TPK6

Proteomic databases

PaxDbiQ7TPK6
PRIDEiQ7TPK6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi65266
RGDi631401 Wnk4

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-RNO-2672351 Stimuli-sensing channels

Miscellaneous databases

PROiPR:Q7TPK6

Gene expression databases

BgeeiENSRNOG00000020441 Expressed in 9 organ(s), highest expression level in adult mammalian kidney
ExpressionAtlasiQ7TPK6 baseline and differential
GenevisibleiQ7TPK6 RN

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
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, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

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: November 7, 2018
This is version 136 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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