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Q7TPK6

- WNK4_RAT

UniProt

Q7TPK6 - WNK4_RAT

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Protein
Serine/threonine-protein kinase WNK4
Gene
Wnk4, Prkwnk4
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.

Catalytic activityi

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

Cofactori

Magnesium By similarity.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 – 1831ATP By similarity
Active sitei299 – 2991Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi177 – 1859ATP By similarity

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
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:Prkwnk4
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.

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 WNK4
PRO_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 autocatalysis By similarityBy similarity
Modified residuei332 – 3321Phosphoserine; by autocatalysis By similarityBy 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.

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 By similarity. Interacts with KLHL3, WNK1 and WNK3 By similarity.By similarity

Protein-protein interaction databases

DIPiDIP-59689N.

Structurei

3D structure databases

ProteinModelPortaliQ7TPK6.
SMRiQ7TPK6. Positions 161-430.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

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.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti9 – 91T → R in AAO18238. 1 Publication
Sequence conflicti204 – 2041T → A in AAO18238. 1 Publication
Sequence conflicti764 – 7641P → A in AAO18238. 1 Publication
Sequence conflicti776 – 7761A → E in AAO18238. 1 Publication
Sequence conflicti1194 – 11941R → K in AAO18238. 1 Publication

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 Kyoto.
    Tissue: Kidney.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar Kyoto.
    Tissue: Kidney.

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: September 3, 2014
This is version 106 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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi