Human Gene WNK2 (ENST00000297954.9) from GENCODE V44
Description: Homo sapiens WNK lysine deficient protein kinase 2 (WNK2), transcript variant 1, mRNA. (from RefSeq NM_001282394) RefSeq Summary (NM_001282394): The protein encoded by this gene is a cytoplasmic serine-threonine kinase that belongs to the protein kinase superfamily. The protein plays an important role in the regulation of electrolyte homeostasis, cell signaling survival, and proliferation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]. Gencode Transcript: ENST00000297954.9 Gencode Gene: ENSG00000165238.17 Transcript (Including UTRs) Position: hg38 chr9:93,184,122-93,319,205 Size: 135,084 Total Exon Count: 31 Strand: + Coding Region Position: hg38 chr9:93,184,930-93,318,027 Size: 133,098 Coding Exon Count: 30
ID:WNK2_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase WNK2; EC=2.7.11.1; AltName: Full=Antigen NY-CO-43; AltName: Full=Protein kinase lysine-deficient 2; AltName: Full=Protein kinase with no lysine 2; AltName: Full=Serologically defined colon cancer antigen 43; 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. Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium (By similarity). ENZYME REGULATION: Activation requires autophosphorylation of Ser- 356. Phosphorylation of Ser-352 also promotes increased activity (By similarity). SUBUNIT: Forms a complex with the phosphorylated form of STK39 (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. TISSUE SPECIFICITY: Expressed in various cancer cell lines (at protein level). Predominantly expressed in heart, brain, skeletal muscle and colon. PTM: Autophosphorylated. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. SIMILARITY: Contains 1 protein kinase domain. CAUTION: Cys-224 is present instead of the conserved Lys which is expected to be an active site residue. Lys-207 appears to fulfill the required catalytic function. SEQUENCE CAUTION: Sequence=AAH37965.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y3S1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0008285 negative regulation of cell proliferation GO:0016310 phosphorylation GO:0035556 intracellular signal transduction GO:0046777 protein autophosphorylation GO:0050801 ion homeostasis GO:0070373 negative regulation of ERK1 and ERK2 cascade GO:0090263 positive regulation of canonical Wnt signaling pathway GO:2000651 positive regulation of sodium ion transmembrane transporter activity