WNK3 WNK lysine deficient protein kinase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: WNK3provided by HGNC
Official Full Name: WNK lysine deficient protein kinase 3provided by HGNC
Primary source: HGNC:HGNC:14543
See related: Ensembl:ENSG00000196632 MIM:300358; AllianceGenome:HGNC:14543
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PRS; MRXS2; PRKWNK3
Summary: This gene encodes a protein belonging to the 'with no lysine' family of serine-threonine protein kinases. These family members lack the catalytic lysine in subdomain II, and instead have a conserved lysine in subdomain I. This family member functions as a positive regulator of the transcellular Ca2+ transport pathway, and it plays a role in the increase of cell survival in a caspase-3-dependent pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
Expression: Biased expression in testis (RPKM 7.2), brain (RPKM 1.1) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp11.22

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (54192823..54358900, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (53482708..53648791, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (54219256..54384479, complement)

Chromosome X - NC_000023.11 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

WNK3 inhibition elicits antitumor immunity by suppressing PD-L1 expression on tumor cells and activating T-cell function.
Title: WNK3 inhibition elicits antitumor immunity by suppressing PD-L1 expression on tumor cells and activating T-cell function.
WNKs are potassium-sensitive kinases.
Title: WNKs are potassium-sensitive kinases.
Advances in the study of the role and molecular mechanism of withnolysine kinase 3 in nervous system diseases (Review).
Title: Advances in the study of the role and molecular mechanism of with‑no‑lysine kinase 3 in nervous system diseases (Review).
A Phosphorylated Intermediate in the Activation of WNK Kinases.
Title: A Phosphorylated Intermediate in the Activation of WNK Kinases.
This study demonstrated that the WNK3 up regulation in hippocampal specimens from epileptic patients with hippocampal sclerosis.
Title: Increased expression of WNK3 in dispersed granule cells in hippocampal sclerosis of mesial temporal lobe epilepsy patients.
Data show that WNK lysine deficient protein kinase 3 protein (WNK3) interacts with NCC and increases the Na-Cl cotransporter (NCC) expression on the cell membrane and in cytoplasm together.
Title: WNK3 interacts with NCC.
WNK3 enhances NCC protein expression by increasing NCC synthesis via an ERK 1/2-dependent signaling pathway
Title: WNK3 Kinase Enhances the Sodium Chloride Cotransporter Expression via an ERK 1/2 Signaling Pathway.
WNK3 knockout mice exhibited significantly decreased infarct volume in a transgenic model of stroke and brain damage.
Title: Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery After Stroke.
There may be a novel role for WNK3 on the renal Na+-Cl-cotransporter (NCC) expression at the plasma membrane, an effect apparently independent of the SPAK kinase and the aldosterone-SGK1 pathway.
Title: WNK3 abrogates the NEDD4-2-mediated inhibition of the renal Na+-Cl- cotransporter.
LINGO-1 potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity.
Title: LINGO-1 receptor promotes neuronal apoptosis by inhibiting WNK3 kinase activity.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Prieto syndrome MedGen: C1839730 OMIM: 309610 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DXS7533 (e-PCR)
- UniSTS:44079

D8S2279 (e-PCR)
- UniSTS:473907

RH26059 (e-PCR)
- UniSTS:87638

SGC31719 (e-PCR)
- UniSTS:57948

STS-M78294 (e-PCR)
- UniSTS:66915

DXS8325 (e-PCR)
- UniSTS:67959

DXS1013E (e-PCR)
- UniSTS:1159

DXS7567 (e-PCR)
- UniSTS:99207

X99131 (e-PCR)
- UniSTS:28313

D1S3688 (e-PCR)
- UniSTS:474266

RH98462 (e-PCR)
- UniSTS:83616

SHGC-106582 (e-PCR)
- UniSTS:185033

SHGC-144031 (e-PCR)
- UniSTS:185062

RH99195 (e-PCR)
- UniSTS:92914

Gene Ontology Provided by GOA

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 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	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay 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	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 DNA damage response	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell volume homeostasis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of cell volume homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell volume homeostasis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular hyperosmotic response	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within maintenance of blood-brain barrier	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in membraneless organelle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of pancreatic juice secretion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of osmosensory signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of sodium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of sodium ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	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 calcium ion import	IMP Inferred from Mutant Phenotype more info	PubMed
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	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Component	Evidence Code	Pubs
located_in adherens junction	ISS Inferred from Sequence or Structural Similarity more info
located_in bicellular tight junction	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase WNK3

Names: Prieto X-linked mental retardation syndrome; protein kinase with no lysine 3

NP_001002838.1

EC 2.7.11.1

NP_001382095.1

EC 2.7.11.1

NP_065973.2

EC 2.7.11.1

XP_011529104.1

EC 2.7.11.1

XP_016885230.1

EC 2.7.11.1

XP_016885231.1

EC 2.7.11.1

XP_016885232.1

EC 2.7.11.1

XP_016885233.1

EC 2.7.11.1

XP_016885234.1

EC 2.7.11.1

XP_047298332.1

EC 2.7.11.1

XP_047298333.1

EC 2.7.11.1

XP_047298334.1

EC 2.7.11.1

XP_047298335.1

EC 2.7.11.1

XP_047298336.1

EC 2.7.11.1

XP_047298337.1

EC 2.7.11.1

XP_047298338.1

EC 2.7.11.1

XP_047298339.1

EC 2.7.11.1

XP_047298340.1

EC 2.7.11.1

XP_047298341.1

EC 2.7.11.1

XP_047298342.1

EC 2.7.11.1

XP_047298343.1

EC 2.7.11.1

XP_047298344.1

EC 2.7.11.1

XP_054183574.1

EC 2.7.11.1

XP_054183575.1

EC 2.7.11.1

XP_054183576.1

EC 2.7.11.1

XP_054183577.1

EC 2.7.11.1

XP_054183578.1

EC 2.7.11.1

XP_054183579.1

EC 2.7.11.1

XP_054183580.1

EC 2.7.11.1

XP_054183581.1

EC 2.7.11.1

XP_054183582.1

EC 2.7.11.1

XP_054183583.1

EC 2.7.11.1

XP_054183584.1

EC 2.7.11.1

XP_054183585.1

EC 2.7.11.1

XP_054183586.1

EC 2.7.11.1

XP_054183587.1

EC 2.7.11.1

XP_054183588.1

EC 2.7.11.1

XP_054183589.1

EC 2.7.11.1

XP_054183590.1

EC 2.7.11.1

XP_054183591.1

EC 2.7.11.1

XP_054183592.1

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.

Genomic

NG_021259.2 RefSeqGene

Range

5001..170183

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001002838.4 → NP_001002838.1 serine/threonine-protein kinase WNK3 isoform 2

See identical proteins and their annotated locations for NP_001002838.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region and lacks an alternate in-frame exon in the 3' coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

AJ409088, AL591766, AY352048, R44257, Z84469

Consensus CDS

CCDS35302.1

UniProtKB/Swiss-Prot

Q9BYP7

Related

ENSP00000364312.3, ENST00000375169.7

Conserved Domains (2) summary

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 489

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
NM_001395166.1 → NP_001382095.1 serine/threonine-protein kinase WNK3 isoform 2

Status: REVIEWED

Source sequence(s)

AL049793, AL591766, Z84469

Consensus CDS

CCDS35302.1

Conserved Domains (2) summary

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 489

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
NM_020922.5 → NP_065973.2 serine/threonine-protein kinase WNK3 isoform 1

See identical proteins and their annotated locations for NP_065973.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL591766, AY352048, R44257, Z84469

Consensus CDS

CCDS14357.1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6

Related

ENSP00000346667.2, ENST00000354646.7

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

54192823..54358900 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047442382.1 → XP_047298338.1 serine/threonine-protein kinase WNK3 isoform X4
XM_047442379.1 → XP_047298335.1 serine/threonine-protein kinase WNK3 isoform X3
XM_017029744.2 → XP_016885233.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal
XM_047442383.1 → XP_047298339.1 serine/threonine-protein kinase WNK3 isoform X4
XM_047442381.1 → XP_047298337.1 serine/threonine-protein kinase WNK3 isoform X4
XM_047442378.1 → XP_047298334.1 serine/threonine-protein kinase WNK3 isoform X3
XM_017029743.2 → XP_016885232.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal
XM_011530802.3 → XP_011529104.1 serine/threonine-protein kinase WNK3 isoform X3

See identical proteins and their annotated locations for XP_011529104.1

UniProtKB/Swiss-Prot

Q9BYP7

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal
XM_017029745.2 → XP_016885234.1 serine/threonine-protein kinase WNK3 isoform X2

UniProtKB/Swiss-Prot

Q9BYP7
XM_017029741.2 → XP_016885230.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal
XM_047442380.1 → XP_047298336.1 serine/threonine-protein kinase WNK3 isoform X4
XM_047442376.1 → XP_047298332.1 serine/threonine-protein kinase WNK3 isoform X3
XM_017029742.2 → XP_016885231.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6

Conserved Domains (3) summary

smart00220
Location:152 → 405

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14031
Location:136 → 410

STKc_WNK3; Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3

pfam12202
Location:426 → 463

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal
XM_047442377.1 → XP_047298333.1 serine/threonine-protein kinase WNK3 isoform X3
XM_047442388.1 → XP_047298344.1 serine/threonine-protein kinase WNK3 isoform X5
XM_047442387.1 → XP_047298343.1 serine/threonine-protein kinase WNK3 isoform X5
XM_047442384.1 → XP_047298340.1 serine/threonine-protein kinase WNK3 isoform X5
XM_047442385.1 → XP_047298341.1 serine/threonine-protein kinase WNK3 isoform X5
XM_047442386.1 → XP_047298342.1 serine/threonine-protein kinase WNK3 isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060947.1 Alternate T2T-CHM13v2.0

Range

53482708..53648791 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054327611.1 → XP_054183586.1 serine/threonine-protein kinase WNK3 isoform X4
XM_054327608.1 → XP_054183583.1 serine/threonine-protein kinase WNK3 isoform X3
XM_054327602.1 → XP_054183577.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6
XM_054327612.1 → XP_054183587.1 serine/threonine-protein kinase WNK3 isoform X4
XM_054327610.1 → XP_054183585.1 serine/threonine-protein kinase WNK3 isoform X4
XM_054327607.1 → XP_054183582.1 serine/threonine-protein kinase WNK3 isoform X3
XM_054327601.1 → XP_054183576.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6
XM_054327609.1 → XP_054183584.1 serine/threonine-protein kinase WNK3 isoform X4
XM_054327605.1 → XP_054183580.1 serine/threonine-protein kinase WNK3 isoform X3
XM_054327600.1 → XP_054183575.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6
XM_054327604.1 → XP_054183579.1 serine/threonine-protein kinase WNK3 isoform X3
XM_054327603.1 → XP_054183578.1 serine/threonine-protein kinase WNK3 isoform X2
XM_054327599.1 → XP_054183574.1 serine/threonine-protein kinase WNK3 isoform X1

UniProtKB/Swiss-Prot

B1AKG2, Q5JRC1, Q6JP76, Q8TCX6, Q9BYP7, Q9HCK6
XM_054327606.1 → XP_054183581.1 serine/threonine-protein kinase WNK3 isoform X3
XM_054327617.1 → XP_054183592.1 serine/threonine-protein kinase WNK3 isoform X5
XM_054327616.1 → XP_054183591.1 serine/threonine-protein kinase WNK3 isoform X5
XM_054327614.1 → XP_054183589.1 serine/threonine-protein kinase WNK3 isoform X5
XM_054327613.1 → XP_054183588.1 serine/threonine-protein kinase WNK3 isoform X5
XM_054327615.1 → XP_054183590.1 serine/threonine-protein kinase WNK3 isoform X5