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Wnk3 WNK lysine deficient protein kinase 3 [ Mus musculus (house mouse) ]

Gene ID: 279561, updated on 21-Apr-2024

Summary

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Official Symbol
Wnk3provided by MGI
Official Full Name
WNK lysine deficient protein kinase 3provided by MGI
Primary source
MGI:MGI:2652875
See related
Ensembl:ENSMUSG00000041245 AllianceGenome:MGI:2652875
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
Prkwnk3; Wnk3-ps
Summary
Predicted to enable chloride channel inhibitor activity; potassium channel inhibitor activity; and protein serine/threonine kinase activity. Involved in negative regulation of pancreatic juice secretion. Acts upstream of or within cell volume homeostasis and maintenance of blood-brain barrier. Located in adherens junction and bicellular tight junction. Orthologous to human WNK3 (WNK lysine deficient protein kinase 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Biased expression in whole brain E14.5 (RPKM 3.2), CNS E18 (RPKM 3.1) and 8 other tissues See more
Orthologs
human all
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Genomic context

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Location:
X F3; X 68.46 cM
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) X NC_000086.8 (149951774..150103190)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) X NC_000086.7 (151168777..151320194)

Chromosome X - NC_000086.8Genomic Context describing neighboring genes Neighboring gene 40S ribosomal protein S25 pseudogene Neighboring gene ribosomal protein S12, pseudogene 7 Neighboring gene ribosomal protein L21, pseudogene 15 Neighboring gene STARR-seq mESC enhancer starr_48079 Neighboring gene STARR-seq mESC enhancer starr_48080 Neighboring gene predicted gene, 26441 Neighboring gene RIKEN cDNA A230072E10 gene Neighboring gene STARR-positive B cell enhancer mm9_chrX:147778291-147778592 Neighboring gene family with sequence similarity 120, member C Neighboring gene importin 5 pseudogene Neighboring gene predicted gene, 22248

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse. Mederle K, et al. Am J Physiol Renal Physiol, 2013 May 1. PMID 23427142
  2. A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo. Oi K, et al. Biol Open, 2012 Feb 15. PMID 23213404, Free PMC Article
  3. WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1). Leng Q, et al. J Physiol, 2006 Mar 1. PMID 16357011, Free PMC Article
  4. WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability. Kahle KT, et al. Proc Natl Acad Sci U S A, 2005 Nov 15. PMID 16275911, Free PMC Article
  5. WNK3 Maintains the GABAergic Inhibitory Tone, Synaptic Excitation and Neuronal Excitability via Regulation of KCC2 Cotransporter in Mature Neurons. Lim WM, et al. Front Mol Neurosci, 2021. PMID 34858138, Free PMC Article

See all (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. WNK kinase-dependent pathway can affect both the trafficking as well as intrinsic activity of NKCC2.
    Title: Regulation of Na(+)-K(+)-Cl(-) cotransporter type 2 by the with no lysine kinase-dependent signaling pathway.
  2. WNK3 knockout mice show faster neurological functional recovery after occlusion of the left middle cerebral artery.
    Title: Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke.
  3. angiotensin II activates the WNK-SPAK-NKCC1 phosphorylation cascade through the angiotensin II type 1 receptor. activation of the WNK-SPAK-NKCC1 phosphorylation cascade induced by a low-salt diet and angiotensin II is dependent on WNK3.
    Title: Dietary salt intake regulates WNK3-SPAK-NKCC1 phosphorylation cascade in mouse aorta through angiotensin II.
  4. WNK3 may serve as a member of a kinase network that facilitates the fine-tuning of renal transepithelial NaCl transport.
    Title: Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse.
  5. WNK3 increases the cytoplasmic localization of Fox-1, thereby suppressing Fox-1-dependent mrna splicing.
    Title: Protein kinase WNK3 regulates the neuronal splicing factor Fox-1.
  6. effects of WNK3 on these transporters and their coexpression in renal epithelia implicate WNK3 in NaCl, water, and blood pressure homeostasis, perhaps via signaling downstream of vasopressin
    Title: WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis.
  7. suggest that WNK3 is part of the Cl(-)/volume-sensing mechanism necessary for the maintenance of cell volume during osmotic stress and the dynamic modulation of GABA neurotransmission
    Title: WNK3 modulates transport of Cl- in and out of cells: implications for control of cell volume and neuronal excitability.
  8. WNK3 is likely a component of one of the mechanisms that determines the balance between renal NaCl reabsorption and K+ secretion.
    Title: WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1).
Submit: New GeneRIF Correction

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Gene trapped (3) 
  • Targeted (1)  1 citation
  • Endonuclease-mediated (4) 

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables molecular condensate scaffold activity ISO
Inferred from Sequence Orthology
more info
  
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables potassium channel inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein serine/threonine kinase activity ISO
Inferred from Sequence Orthology
more info
  
enables transferase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within cell volume homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of cell volume homeostasis ISO
Inferred from Sequence Orthology
more info
  
involved_in cellular hyperosmotic response ISO
Inferred from Sequence Orthology
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within maintenance of blood-brain barrier 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 ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of apoptotic process ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of pancreatic juice secretion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of protein localization to plasma membrane ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of sodium ion transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in non-membrane-bounded organelle assembly ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of osmosensory signaling pathway ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of peptidyl-threonine phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of calcium ion transport ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of ion transmembrane transporter activity ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of peptidyl-threonine phosphorylation ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of potassium ion import across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of protein localization to plasma membrane ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of sodium ion transmembrane transporter activity ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of sodium ion transport ISO
Inferred from Sequence Orthology
more info
  
involved_in protein autophosphorylation ISO
Inferred from Sequence Orthology
more info
  
involved_in protein localization to plasma membrane ISO
Inferred from Sequence Orthology
more info
  
involved_in protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of calcium ion import ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of regulation of monoatomic cation transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of regulation of monoatomic cation transmembrane transport ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
located_in adherens junction IDA
Inferred from Direct Assay
more info
 PubMed 
located_in bicellular tight junction IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm ISO
Inferred from Sequence Orthology
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase WNK3
Names
WNK lysine deficient protein kinase 3, pseudogene
protein kinase lysine-deficient 3
protein kinase with no lysine 3
NP_001258607.1
NP_001258608.1
XP_006528933.1
XP_006528934.1
XP_006528935.1
XP_006528936.1
XP_011246131.1
XP_011246132.1
XP_030107222.1
XP_030107223.1
XP_036017870.1

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)

  1. NM_001271678.1 → NP_001258607.1  serine/threonine-protein kinase WNK3 isoform 1

    See identical proteins and their annotated locations for NP_001258607.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) is the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK034405, AL807396, BB676704, BC043119, CD350795, CF748862, CX566674, JQ247189
    Consensus CDS
    CCDS72451.1
    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Related
    ENSMUSP00000139037.2, ENSMUST00000184392.8
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  2. NM_001271679.1 → NP_001258608.1  serine/threonine-protein kinase WNK3 isoform 2

    See identical proteins and their annotated locations for NP_001258608.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) has an alternated splice site in the coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
    Source sequence(s)
    AK034405, BB676704, BC043119, CD350795, CF748862, CX566674, JQ247190
    Consensus CDS
    CCDS72450.1
    UniProtKB/TrEMBL
    V9GWU7
    Related
    ENSMUSP00000138822.2, ENSMUST00000184730.8
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

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

  1. NC_000086.8 Reference GRCm39 C57BL/6J

    Range
    149951774..150103190
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006528871.5 → XP_006528934.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_006528934.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  2. XM_006528870.5 → XP_006528933.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_006528933.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  3. XM_006528872.5 → XP_006528935.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_006528935.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  4. XM_011247830.4 → XP_011246132.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_011246132.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  5. XM_006528873.5 → XP_006528936.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_006528936.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  6. XM_030251363.2 → XP_030107223.1  serine/threonine-protein kinase WNK3 isoform X2

    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  7. XM_036161977.1 → XP_036017870.1  serine/threonine-protein kinase WNK3 isoform X2

    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  8. XM_030251362.1 → XP_030107222.1  serine/threonine-protein kinase WNK3 isoform X1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

  9. XM_011247829.4 → XP_011246131.1  serine/threonine-protein kinase WNK3 isoform X1

    See identical proteins and their annotated locations for XP_011246131.1

    UniProtKB/Swiss-Prot
    H6WJI2, H6WJI3, Q80XP9
    UniProtKB/TrEMBL
    V9GWU7
    Conserved Domains (2) summary
    cd14031
    Location:135 → 409
    STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3
    pfam12202
    Location:425 → 488
    OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q80XP9.3 GenPept UniProtKB/Swiss-Prot:Q80XP9

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