Wnk4 WNK lysine deficient protein kinase 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Wnk4provided by RGD
Official Full Name: WNK lysine deficient protein kinase 4provided by RGD
Primary source: RGD:631401
See related: Ensembl:ENSRNOG00000020441 AllianceGenome:RGD:631401
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Ac2-059; Prkwnk4
Summary: Enables protein serine/threonine kinase activity. Involved in negative regulation of sodium ion transport and protein phosphorylation. Located in cytosol and membrane. Biomarker of transient cerebral ischemia. 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, Apr 2022]
Expression: Biased expression in Kidney (RPKM 82.3), Thymus (RPKM 26.6) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 10q31

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (86702828..86719917)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (86202552..86219655)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (89181139..89198213)

Chromosome 10 - NC_086028.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

in addition to SPAK and OSR1, WNK4 is able to anchor itself to the N-terminal domain of NKCC1 and to promote cotransporter activation.
Title: A novel Ste20-related proline/alanine-rich kinase (SPAK)-independent pathway involving calcium-binding protein 39 (Cab39) and serine threonine kinase with no lysine member 4 (WNK4) in the activation of Na-K-Cl cotransporters.
results define a previously undescribed function of WNK4 and reveal a unique therapeutic target to control blood pressure in WNK4-related hypertension
Title: Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature.
salt loading suppressed renal WNK4 expression, activated the Na(+)-Cl(-) cotransporter and induced salt-dependent hypertension
Title: Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.
Wnk4 phosphorylates ser(206) of claudin-7 and promotes paracellular Cl-ion permeability.
Title: WNK4 phosphorylates ser(206) of claudin-7 and promotes paracellular Cl(-) permeability.
WNK1 and WNK4 exhibit additive CFTR inhibition. FHHt-causing mutant WNK4 Q562E is a more potent inhibitor of CFTR activity than is the wild-type WNK4.
Title: WNK1 and WNK4 modulate CFTR activity.
WNK4 has a key role in coordinating the activities of diverse flux pathways to achieve integrated fluid and electrolyte homeostasis
Title: WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo.
WNK1 and WNK4 both interacted with SPAK as well as a closely related kinase, termed oxidative stress response kinase-1 (OSR1).
Title: The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases.
Our results reveal that WNK4 regulates the activity of the K(+)-Cl(-) cotransporters expressed in the kidney.
Title: WNK4 kinase is a negative regulator of K+-Cl- cotransporters.
Gene analysis of rat chromosome 10 suggest that Wnk4 does not have a role in polygenic hypertension.
Title: The role of Wnk4 in polygenic hypertension: a candidate gene analysis on rat chromosome 10.

Submit: New GeneRIF Correction

General gene information

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Markers

RH137051 (e-PCR)
- UniSTS:219140

AW107467 (e-PCR)
- UniSTS:180322

RH128509 (e-PCR)
- UniSTS:211817

PMC357052P1 (e-PCR)
- UniSTS:273302

RH124894 (e-PCR)
- UniSTS:161716

RH134547 (e-PCR)
- UniSTS:217827

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP binding	ISS Inferred from Sequence or Structural Similarity more info
enables chloride ion binding	ISO Inferred from Sequence Orthology more info
enables ion channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables ion channel inhibitor 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 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	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
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

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in aldosterone secretion	ISO Inferred from Sequence Orthology more info
involved_in calcium ion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cellular response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within chloride transport	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
involved_in inflammatory response	ISO Inferred from Sequence Orthology more info
involved_in intracellular chloride ion homeostasis	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
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 monoatomic ion homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in multivesicular body sorting pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of pancreatic juice secretion	ISO Inferred from Sequence Orthology more info
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 negative regulation of sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
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	ISO Inferred from Sequence Orthology more info
involved_in protein kinase C signaling	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein localization	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood pressure	ISO Inferred from Sequence Orthology more info
involved_in regulation of potassium ion export across plasma membrane	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in renal sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to dietary excess	ISO Inferred from Sequence Orthology more info
involved_in response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of ESCRT II complex	IEA Inferred from Electronic Annotation more info
located_in bicellular tight junction	ISO Inferred from Sequence Orthology more info
located_in bicellular tight junction	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cell body	ISO Inferred from Sequence Orthology more info
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
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: serine/threonine-protein kinase WNK4

Names: WNK4 Ser/Thr kinase; protein kinase lysine-deficient 4; protein kinase with no lysine 4

NP_783169.2

EC 2.7.11.1

XP_006247340.1

EC 2.7.11.1

XP_006247341.1

EC 2.7.11.1

XP_006247342.1

EC 2.7.11.1

XP_006247343.1

EC 2.7.11.1

XP_038941545.1

EC 2.7.11.1

XP_038941547.1

EC 2.7.11.1

XP_063124808.1

EC 2.7.11.1

XP_063124809.1

EC 2.7.11.1

XP_063124810.1

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_175579.3 → NP_783169.2 serine/threonine-protein kinase WNK4

Status: VALIDATED

Source sequence(s)

AY187039, AY192567, BQ211864

UniProtKB/Swiss-Prot

Q7TPK6, Q810H4, Q811R5

UniProtKB/TrEMBL

A6HJA0

Related

ENSRNOP00000027770.5, ENSRNOT00000027770.8

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_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086028.1 Reference GRCr8

Range

86702828..86719917

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039085619.2 → XP_038941547.1 serine/threonine-protein kinase WNK4 isoform X9

Conserved Domains (2) summary

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_039085617.2 → XP_038941545.1 serine/threonine-protein kinase WNK4 isoform X4

UniProtKB/Swiss-Prot

Q7TPK6, Q810H4, Q811R5

UniProtKB/TrEMBL

A6HJA0

Conserved Domains (2) summary

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_006247279.5 → XP_006247341.1 serine/threonine-protein kinase WNK4 isoform X2

UniProtKB/Swiss-Prot

Q7TPK6, Q810H4, Q811R5

UniProtKB/TrEMBL

A6HJA0

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
XM_006247278.5 → XP_006247340.1 serine/threonine-protein kinase WNK4 isoform X1

UniProtKB/Swiss-Prot

Q7TPK6, Q810H4, Q811R5

UniProtKB/TrEMBL

A0A096MKH1, A6HJA0

Related

ENSRNOP00000068513.2

Conserved Domains (2) summary

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_063268738.1 → XP_063124808.1 serine/threonine-protein kinase WNK4 isoform X3
XM_006247280.5 → XP_006247342.1 serine/threonine-protein kinase WNK4 isoform X5

UniProtKB/Swiss-Prot

Q7TPK6, Q810H4, Q811R5

UniProtKB/TrEMBL

A0A8I5ZQR6, A6HJA0

Related

ENSRNOP00000080834.1

Conserved Domains (3) summary

smart00220
Location:17 → 241

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam12202
Location:262 → 298

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

cl21453
Location:14 → 241

PKc_like; Protein Kinases, catalytic domain
XM_063268739.1 → XP_063124809.1 serine/threonine-protein kinase WNK4 isoform X7
XM_006247281.5 → XP_006247343.1 serine/threonine-protein kinase WNK4 isoform X6

Conserved Domains (3) summary

smart00220
Location:1 → 161

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam12202
Location:182 → 218

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

cl21453
Location:1 → 161

PKc_like; Protein Kinases, catalytic domain
XM_063268740.1 → XP_063124810.1 serine/threonine-protein kinase WNK4 isoform X8