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

Summary

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 molecular condensate scaffold 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. Human ortholog(s) of this gene implicated in Prieto syndrome. Orthologous to human WNK3 (WNK lysine deficient protein kinase 3). [provided by Alliance of Genome Resources, Nov 2024]
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

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_000086.8 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 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?

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.
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.
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.
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.
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.
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.
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.
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).

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Variation

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Alleles

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

Endonuclease-mediated (4)
Gene trapped (3)
Targeted (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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	IEA Inferred from Electronic Annotation 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 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 molecular condensate scaffold activity	ISO Inferred from Sequence Orthology more info
enables molecular condensate scaffold activity	ISS Inferred from Sequence or Structural Similarity 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 kinase activity	ISS Inferred from Sequence or Structural Similarity more info
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	ISO Inferred from Sequence Orthology more info
enables ribosomal protein S6 kinase 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 cell volume homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cellular hyperosmotic response	ISO Inferred from Sequence Orthology more info
involved_in cellular hyperosmotic response	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation 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 membraneless organelle assembly	ISO Inferred from Sequence Orthology more info
involved_in membraneless organelle assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation 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 protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of sodium ion transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in osmosensory signaling pathway	IEA Inferred from Electronic Annotation 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
involved_in positive regulation of calcium ion transport	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 ion transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of peptidyl-threonine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of peptidyl-threonine phosphorylation	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 positive regulation of protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity 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 transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in protein localization to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of calcium ion import	ISO Inferred from Sequence Orthology more info
involved_in regulation of calcium ion import	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology 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

EC 2.7.11.1

NP_001258608.1

EC 2.7.11.1

XP_006528933.1

EC 2.7.11.1

XP_006528934.1

EC 2.7.11.1

XP_006528935.1

EC 2.7.11.1

XP_006528936.1

EC 2.7.11.1

XP_011246131.1

EC 2.7.11.1

XP_011246132.1

EC 2.7.11.1

XP_030107222.1

EC 2.7.11.1

XP_030107223.1

EC 2.7.11.1

XP_036017870.1

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_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

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
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

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

NC_000086.8 Reference GRCm39 C57BL/6J

Range

149951774..150103190

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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
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

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
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

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
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

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
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

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

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

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

UniProtKB/Swiss-Prot

H6WJI2, H6WJI3, Q80XP9

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
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

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