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Aliases for WNK3 Gene

Aliases for WNK3 Gene

  • WNK Lysine Deficient Protein Kinase 3 2 3 5
  • Protein Kinase With No Lysine 3 3 4
  • EC 2.7.11.1 4 61
  • PRKWNK3 3 4
  • Serine/Threonine-Protein Kinase WNK3 3
  • Protein Kinase, Lysine Deficient 3 2
  • Protein Kinase Lysine-Deficient 3 4
  • EC 2.7.11 61
  • KIAA1566 4

External Ids for WNK3 Gene

Previous HGNC Symbols for WNK3 Gene

  • PRKWNK3

Previous GeneCards Identifiers for WNK3 Gene

  • GC0XM054106
  • GC0XM051270

Summaries for WNK3 Gene

Entrez Gene Summary for WNK3 Gene

  • 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]

GeneCards Summary for WNK3 Gene

WNK3 (WNK Lysine Deficient Protein Kinase 3) is a Protein Coding gene. Diseases associated with WNK3 include Syndromic X-Linked Intellectual Disability Siderius Type and Lung Large Cell Carcinoma. Among its related pathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Diuretics Pathway, Pharmacodynamics. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is WNK2.

UniProtKB/Swiss-Prot for WNK3 Gene

  • Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:16275913, PubMed:16275911, PubMed:16357011). Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.

  • Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686, isoform 1 inhibits the activity of SLC12A3.

Gene Wiki entry for WNK3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for WNK3 Gene

Genomics for WNK3 Gene

Regulatory Elements for WNK3 Gene

Enhancers for WNK3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH0XG054357 0.9 ENCODE 0.7 +0.2 195 2.5 ZNF76 THRB YY1 ETS1 GLIS2 ZNF366 ZNF143 EGR2 SP3 REST WNK3 RNU6-434P
GH0XG054387 0.6 ENCODE 0.3 -29.4 -29371 1.0 CEBPA HLF TCF7 CEBPB PRDM10 SMAD4 BCL6 WNK3 GC0XP054426
GH0XG054420 0.6 ENCODE 0.2 -61.4 -61428 0.2 SOX13 JUND ATF3 HNF4G KDM1A HNF4A NR3C1 NR2F2 YY1 GC0XP054426 WNK3
GH0XG054415 0.4 ENCODE 0.2 -57.3 -57253 0.9 BCL6B ZMYM3 GC0XP054426 WNK3
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around WNK3 on UCSC Golden Path with GeneCards custom track

Promoters for WNK3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000246734 494 2399 PKNOX1 ZNF76 THRB YY1 ETS1 GLIS2 ZNF366 ZNF143 EGR2 SP3

Genomic Location for WNK3 Gene

Chromosome:
X
Start:
54,192,823 bp from pter
End:
54,358,695 bp from pter
Size:
165,873 bases
Orientation:
Minus strand

Genomic View for WNK3 Gene

Genes around WNK3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
WNK3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for WNK3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for WNK3 Gene

Proteins for WNK3 Gene

  • Protein details for WNK3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BYP7-WNK3_HUMAN
    Recommended name:
    Serine/threonine-protein kinase WNK3
    Protein Accession:
    Q9BYP7
    Secondary Accessions:
    • B1AKG2
    • Q5JRC1
    • Q6JP76
    • Q8TCX6
    • Q9HCK6

    Protein attributes for WNK3 Gene

    Size:
    1800 amino acids
    Molecular mass:
    198416 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with WNK1 and WNK4.

    Alternative splice isoforms for WNK3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for WNK3 Gene

Selected DME Specific Peptides for WNK3 Gene

Q9BYP7:
  • FTDDLHKLVD
  • PPIIHRD
  • QRFKEEAEMLKGLQHPNIVRFYDSWES
  • EYPYSEC
  • KMVTFKFD
  • KIGDLGLA
  • VIGTPEFMAPE
  • PEVKEIIEGCIR
  • FGMCMLEM
  • TELMTSGTL
  • KDNEAIEFSF
  • KVTSGIKP
  • GTPEFMAPE
  • DLLNHAFF
  • IHRDLKCDNIF
  • YDESVDV
  • VEVAWCELQDRKLTK

Post-translational modifications for WNK3 Gene

  • Ubiquitinated by the BCR(KLHL2) complex, leading to its degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for WNK3 Gene

Gene Families for WNK3 Gene

Protein Domains for WNK3 Gene

Graphical View of Domain Structure for InterPro Entry

Q9BYP7

UniProtKB/Swiss-Prot:

WNK3_HUMAN :
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.
genes like me logo Genes that share domains with WNK3: view

Function for WNK3 Gene

Molecular function for WNK3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activation requires autophosphorylation of Ser-308. Phosphorylation of Ser-304 also promotes increased activity (By similarity). Kinase activity is inhibited by WNK4.
UniProtKB/Swiss-Prot Function:
Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:16275913, PubMed:16275911, PubMed:16357011). Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). Inhibits the activity of KCNJ1 by decreasing its expression at the cell membrane in a non-catalytic manner.
UniProtKB/Swiss-Prot Function:
Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686, isoform 1 inhibits the activity of SLC12A3.

Enzyme Numbers (IUBMB) for WNK3 Gene

Gene Ontology (GO) - Molecular Function for WNK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IDA,IEA 16275913
GO:0004674 protein serine/threonine kinase activity ISS,IEA --
GO:0005515 protein binding IPI 16501604
GO:0005524 ATP binding ISS,IEA --
GO:0016301 kinase activity IEA --
genes like me logo Genes that share ontologies with WNK3: view
genes like me logo Genes that share phenotypes with WNK3: view

Animal Models for WNK3 Gene

MGI Knock Outs for WNK3:

Animal Model Products

  • Taconic Biosciences Mouse Models for WNK3

CRISPR Products

miRNA for WNK3 Gene

miRTarBase miRNAs that target WNK3

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for WNK3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for WNK3 Gene

Localization for WNK3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for WNK3 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for WNK3 gene
Compartment Confidence
cytosol 4
nucleus 3
plasma membrane 1

Gene Ontology (GO) - Cellular Components for WNK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 16501604
GO:0005829 cytosol IBA --
GO:0005912 adherens junction IEA,ISS --
GO:0005923 bicellular tight junction IEA,ISS --
genes like me logo Genes that share ontologies with WNK3: view

Pathways & Interactions for WNK3 Gene

genes like me logo Genes that share pathways with WNK3: view

Pathways by source for WNK3 Gene

Gene Ontology (GO) - Biological Process for WNK3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation ISS,IEA --
GO:0010765 positive regulation of sodium ion transport IDA 16275913
GO:0010800 positive regulation of peptidyl-threonine phosphorylation IDA 16275913
GO:0016310 phosphorylation IEA --
GO:0032414 positive regulation of ion transmembrane transporter activity IDA 16275913
genes like me logo Genes that share ontologies with WNK3: view

No data available for SIGNOR curated interactions for WNK3 Gene

Drugs & Compounds for WNK3 Gene

(2) Drugs for WNK3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(1) Additional Compounds for WNK3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with WNK3: view

Transcripts for WNK3 Gene

Unigene Clusters for WNK3 Gene

WNK lysine deficient protein kinase 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for WNK3

Alternative Splicing Database (ASD) splice patterns (SP) for WNK3 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a ·
SP1:
SP2: - -

ExUns: 24b
SP1:
SP2:

Relevant External Links for WNK3 Gene

GeneLoc Exon Structure for
WNK3
ECgene alternative splicing isoforms for
WNK3

Expression for WNK3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for WNK3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for WNK3 Gene

This gene is overexpressed in Testis (x9.1).

Protein differential expression in normal tissues from HIPED for WNK3 Gene

This gene is overexpressed in Testis (31.9), Fetal Brain (17.2), Lung (8.9), and Ovary (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for WNK3 Gene



Protein tissue co-expression partners for WNK3 Gene

NURSA nuclear receptor signaling pathways regulating expression of WNK3 Gene:

WNK3

SOURCE GeneReport for Unigene cluster for WNK3 Gene:

Hs.92423

mRNA Expression by UniProt/SwissProt for WNK3 Gene:

Q9BYP7-WNK3_HUMAN
Tissue specificity: Expressed in brain, lung, kidney, liver and pancreas, and in fetal tissues including placenta, fetal brain, lung and kidney. Very low levels of expression were also detected in fetal heart, thymus, liver and spleen. Isoform 1 is brain-specific. Isoform 3 is kidney-specific.

Evidence on tissue expression from TISSUES for WNK3 Gene

  • Nervous system(4.5)
  • Liver(4.2)
genes like me logo Genes that share expression patterns with WNK3: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for WNK3 Gene

Orthologs for WNK3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia WNK3 34 35
  • 99.46 (n)
dog
(Canis familiaris)
Mammalia WNK3 34
  • 90.07 (n)
cow
(Bos Taurus)
Mammalia WNK3 34 35
  • 89.96 (n)
mouse
(Mus musculus)
Mammalia Wnk3 34 16 35
  • 86.45 (n)
rat
(Rattus norvegicus)
Mammalia Wnk3 34
  • 85.86 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia WNK3 35
  • 73 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia WNK3 35
  • 48 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 85 (a)
OneToMany
-- 35
  • 39 (a)
OneToMany
zebrafish
(Danio rerio)
Actinopterygii WNK3 35
  • 42 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Wnk 35
  • 18 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea wnk-1 35
  • 23 (a)
OneToMany
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.11318 34
rice
(Oryza sativa)
Liliopsida Os.18183 34
corn
(Zea mays)
Liliopsida Zm.1174 34
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 78 (a)
OneToMany
Species where no ortholog for WNK3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for WNK3 Gene

ENSEMBL:
Gene Tree for WNK3 (if available)
TreeFam:
Gene Tree for WNK3 (if available)

Paralogs for WNK3 Gene

Paralogs for WNK3 Gene

(5) SIMAP similar genes for WNK3 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with WNK3: view

Variants for WNK3 Gene

Sequence variations from dbSNP and Humsavar for WNK3 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
VAR_041324 A lung squamous cell carcinoma sample
VAR_041328 A lung large cell carcinoma sample
VAR_041329 A renal clear cell carcinoma sample
rs1000010948 -- 54,231,007(+) AAATT(C/T)TCTGT intron-variant
rs1000037293 -- 54,200,843(+) ATTTT(A/T)ACAAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for WNK3 Gene

Variant ID Type Subtype PubMed ID
esv2740175 CNV deletion 23290073
nsv435891 CNV deletion 17901297

Variation tolerance for WNK3 Gene

Residual Variation Intolerance Score: 27.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.51; 43.95% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for WNK3 Gene

Human Gene Mutation Database (HGMD)
WNK3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
WNK3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for WNK3 Gene

Disorders for WNK3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for WNK3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
syndromic x-linked intellectual disability siderius type
  • mrxssd
lung large cell carcinoma
  • large cell carcinoma of lung
- elite association - COSMIC cancer census association via MalaCards
Search WNK3 in MalaCards View complete list of genes associated with diseases

Relevant External Links for WNK3

Genetic Association Database (GAD)
WNK3
Human Genome Epidemiology (HuGE) Navigator
WNK3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
WNK3
genes like me logo Genes that share disorders with WNK3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for WNK3 Gene

Publications for WNK3 Gene

  1. Renal and brain isoforms of WNK3 have opposite effects on NCCT expression. (PMID: 19470686) Glover M. … O'Shaughnessy K.M. (J. Am. Soc. Nephrol. 2009) 3 4 22 64
  2. Autism-associated familial microdeletion of Xp11.22. (PMID: 18498374) Qiao Y. … Lewis M.E. (Clin. Genet. 2008) 3 22 46 64
  3. Protein kinase WNK3 increases cell survival in a caspase-3-dependent pathway. (PMID: 16501604) Verissimo F. … Jordan P. (Oncogene 2006) 3 4 22 64
  4. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation- Cl- cotransporters required for normal blood pressure homeostasis. (PMID: 16275913) Rinehart J. … Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 4 22 64
  5. Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3). (PMID: 15194194) Holden S. … Raymond F.L. (Gene 2004) 3 4 22 64

Products for WNK3 Gene

  • Addgene plasmids for WNK3

Sources for WNK3 Gene

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