Wnk4 WNK lysine deficient protein kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Wnk4provided by MGI
Official Full Name: WNK lysine deficient protein kinase 4provided by MGI
Primary source: MGI:MGI:1917097
See related: Ensembl:ENSMUSG00000035112 AllianceGenome:MGI:1917097
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Pha2b; Prkwnk4; 2010002J11Rik
Summary: Enables chloride ion binding activity; ion channel inhibitor activity; and protein serine/threonine kinase activity. Involved in several processes, including ERK1 and ERK2 cascade; metal ion transport; and regulation of protein kinase activity. Acts upstream of or within chloride transport; negative regulation of pancreatic juice secretion; and protein localization. Located in bicellular tight junction and cytoplasm. Part of protein-containing complex. Is active in cell body. Is expressed in several structures, including alimentary system; metanephros; metatarsal bone; sensory organ; and turbinate bone primordium. Used to study Gitelman syndrome and pseudohypoaldosteronism. Human ortholog(s) of this gene implicated in hypertension and pseudohypoaldosteronism. Orthologous to human WNK4 (WNK lysine deficient protein kinase 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in kidney adult (RPKM 36.0), colon adult (RPKM 9.7) and 16 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 D; 11 64.51 cM

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (101151363..101168235)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (101260537..101277409)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.
Title: KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.
Roles of WNK4 and SPAK in K(+)-mediated dephosphorylation of the NaCl cotransporter.
Title: Roles of WNK4 and SPAK in K(+)-mediated dephosphorylation of the NaCl cotransporter.
WNKs are potassium-sensitive kinases.
Title: WNKs are potassium-sensitive kinases.
WNK4 limits distal calcium losses following acute furosemide treatment.
Title: WNK4 limits distal calcium losses following acute furosemide treatment.
Results show that the serine/threonine-protein kinase WNK4 (WNK4)-serine/threonine-protein kinase 39 (SPAK)-NKCC1 transport protein (NKCC1) cascade plays an important role in modulating macrophage activation to regulate lipopolysaccharides (LPS)-induced lung inflammation and lung injury.
Title: WNK4-SPAK modulates lipopolysaccharide-induced macrophage activation.
We postulate a model of distal convoluted tubule function in which NCC activity is modulated by plasma K(+) concentration via WNK4-SPAK/OSR1 interactions within WNK bodies.
Title: WNK bodies cluster WNK4 and SPAK/OSR1 to promote NCC activation in hypokalemia.
single delivery of the vector pair into the mature cochlea of Otof (-/-) mutant mice reconstituted the otoferlin cDNA coding sequence through recombination of the 5' and 3' cDNAs, leading to the durable restoration of otoferlin expression in transduced cells and a reversal of the deafness phenotype, raising hopes for future gene therapy trials in DFNB9 patients
Title: WNK4 kinase is a physiological intracellular chloride sensor.
This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension.
Title: Claudin-7 Modulates Cl(-) and Na(+) Homeostasis and WNK4 Expression in Renal Collecting Duct Cells.
Although these results confirm that familial hyperkalemic hypertension caused by WNK1 mutations is dependent on the activation of SPAK, they suggest that WNK1 and WNK4 play different roles in the distal nephron.
Title: Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1 mutations: evidence for differential roles of WNK1 and WNK4.
Modulation of WNK4 activity by intracellular chloride [Cl(-)]i is not the sole mechanism for regulating NCC. Increased luminal NaCl delivery upregulates NCC via yet unknown mechanism(s) that may override inhibition of WNK4 by high [Cl(-)]i.
Title: Differential roles of WNK4 in regulation of NCC in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (49)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (6) 1 citation
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11Wsu68e (e-PCR), detects polymorphism
- UniSTS:141831

RH66580 (e-PCR)
- UniSTS:89400

AW107467 (e-PCR)
- UniSTS:180322

PMC357052P1 (e-PCR)
- UniSTS:273302

RH124894 (e-PCR)
- UniSTS:161716

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables chloride ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables ion channel inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in aldosterone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to xenobiotic stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chloride transport	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in distal tubule morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in distal tubule morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular chloride ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intracellular chloride ion homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in macrophage activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in monoatomic ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of pancreatic juice secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of sodium ion transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of potassium ion import across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein localization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of potassium ion export across plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal sodium ion absorption	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal sodium ion absorption	ISO Inferred from Sequence Orthology more info
involved_in renal sodium ion absorption	ISS Inferred from Sequence or Structural Similarity more info
involved_in renal sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in response to dietary excess	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to xenobiotic stimulus	IGI Inferred from Genetic Interaction more info	PubMed
involved_in signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in bicellular tight junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in cell body	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase WNK4

Names: protein kinase with no lysine 4; protein kinase, lysine deficient 4

NP_783569.1

EC 2.7.11.1

XP_006534199.1

EC 2.7.11.1

XP_006534200.1

EC 2.7.11.1

XP_006534201.1

EC 2.7.11.1

XP_006534202.1

EC 2.7.11.1

XP_006534204.1

EC 2.7.11.1

XP_017170233.1

EC 2.7.11.1

XP_036012863.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_175638.3 → NP_783569.1 serine/threonine-protein kinase WNK4

See identical proteins and their annotated locations for NP_783569.1

Status: VALIDATED

Source sequence(s)

AL590969, AY187027

Consensus CDS

CCDS25459.1

UniProtKB/Swiss-Prot

A2A4J7, Q4VAC1, Q80UE6, Q80XB5, Q80XN2, Q8R0N0, Q8R340

Related

ENSMUSP00000099397.2, ENSMUST00000103108.8

Conserved Domains (3) summary

smart00220
Location:176 → 429

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 486

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000077.7 Reference GRCm39 C57BL/6J

Range

101151363..101168235

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006534136.2 → XP_006534199.1 serine/threonine-protein kinase WNK4 isoform X1

Conserved Domains (4) summary

PHA03247
Location:737 → 1059

PHA03247; large tegument protein UL36; Provisional

PHA03307
Location:531 → 841

PHA03307; transcriptional regulator ICP4; Provisional

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 512

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_006534139.1 → XP_006534202.1 serine/threonine-protein kinase WNK4 isoform X5

Conserved Domains (4) summary

PHA03247
Location:737 → 1059

PHA03247; large tegument protein UL36; Provisional

PHA03307
Location:531 → 841

PHA03307; transcriptional regulator ICP4; Provisional

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 512

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_006534138.2 → XP_006534201.1 serine/threonine-protein kinase WNK4 isoform X4

Conserved Domains (3) summary

PHA03247
Location:737 → 1059

PHA03247; large tegument protein UL36; Provisional

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 512

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_006534137.2 → XP_006534200.1 serine/threonine-protein kinase WNK4 isoform X2

Conserved Domains (3) summary

PHA03247
Location:746 → 1052

PHA03247; large tegument protein UL36; Provisional

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 512

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_036156970.1 → XP_036012863.1 serine/threonine-protein kinase WNK4 isoform X3

Conserved Domains (3) summary

PHA03247
Location:746 → 1052

PHA03247; large tegument protein UL36; Provisional

cd14033
Location:169 → 429

STKc_WNK4; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4

pfam12202
Location:450 → 512

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_017314744.3 → XP_017170233.1 serine/threonine-protein kinase WNK4 isoform X6

Conserved Domains (4) summary

PHA03247
Location:469 → 791

PHA03247; large tegument protein UL36; Provisional

PHA03307
Location:263 → 573

PHA03307; transcriptional regulator ICP4; Provisional

pfam12202
Location:182 → 244

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

cl21453
Location:1 → 161

PKc_like; Protein Kinases, catalytic domain
XM_006534141.3 → XP_006534204.1 serine/threonine-protein kinase WNK4 isoform X6

See identical proteins and their annotated locations for XP_006534204.1

Conserved Domains (4) summary

PHA03247
Location:469 → 791

PHA03247; large tegument protein UL36; Provisional

PHA03307
Location:263 → 573

PHA03307; transcriptional regulator ICP4; Provisional

pfam12202
Location:182 → 244

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

cl21453
Location:1 → 161

PKc_like; Protein Kinases, catalytic domain