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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Assigned HPA protein class(es) for the encoded protein(s).
Disease related genes Enzymes Human disease related genes Plasma proteins Potential drug targets
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
12
Cytoband
p13.33
Chromosome location (bp)
752579 - 911452
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx 1,2,3,4,5. WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation 6. The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK 7,8,9,10,11,12,13,14,15. Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity 16,17. Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux 18,19. Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation 20. Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L 21. Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm 22. Acts as a negative regulator of autophagy 23. Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade 24. May also play a role in actin cytoskeletal reorganization 25. Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 26. Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization 27....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
ATP-binding, Chloride, Nucleotide-binding
Gene summary (Entrez)i
Useful information about the gene from Entrez
This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Enzymes ENZYME proteins Transferases Kinases MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins Disease related genes Potential drug targets Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0002028[regulation of sodium ion transport] GO:0003084[positive regulation of systemic arterial blood pressure] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004860[protein kinase inhibitor activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006811[ion transport] GO:0007165[signal transduction] GO:0008217[regulation of blood pressure] GO:0010766[negative regulation of sodium ion transport] GO:0010820[positive regulation of T cell chemotaxis] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0018107[peptidyl-threonine phosphorylation] GO:0019869[chloride channel inhibitor activity] GO:0019870[potassium channel inhibitor activity] GO:0019901[protein kinase binding] GO:0019902[phosphatase binding] GO:0030295[protein kinase activator activity] GO:0030644[cellular chloride ion homeostasis] GO:0032991[protein-containing complex] GO:0033633[negative regulation of cell-cell adhesion mediated by integrin] GO:0034115[negative regulation of heterotypic cell-cell adhesion] GO:0034260[negative regulation of GTPase activity] GO:0035556[intracellular signal transduction] GO:0035725[sodium ion transmembrane transport] GO:0038116[chemokine (C-C motif) ligand 21 signaling pathway] GO:0048666[neuron development] GO:0050801[ion homeostasis] GO:0050852[T cell receptor signaling pathway] GO:0055075[potassium ion homeostasis] GO:0055080[cation homeostasis] GO:0090188[negative regulation of pancreatic juice secretion] GO:0090263[positive regulation of canonical Wnt signaling pathway] GO:0097022[lymphocyte migration into lymph node] GO:0106310[protein serine kinase activity] GO:1902305[regulation of sodium ion transmembrane transport] GO:1903038[negative regulation of leukocyte cell-cell adhesion] GO:1903288[positive regulation of potassium ion import across plasma membrane] GO:1904062[regulation of cation transmembrane transport] GO:1990869[cellular response to chemokine] GO:2000651[positive regulation of sodium ion transmembrane transporter activity]
Enzymes ENZYME proteins Transferases Kinases MEMSAT-SVM predicted membrane proteins Phobius predicted membrane proteins THUMBUP predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins Disease related genes Potential drug targets Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0002028[regulation of sodium ion transport] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004860[protein kinase inhibitor activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006811[ion transport] GO:0007165[signal transduction] GO:0010766[negative regulation of sodium ion transport] GO:0010820[positive regulation of T cell chemotaxis] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0018107[peptidyl-threonine phosphorylation] GO:0019869[chloride channel inhibitor activity] GO:0019870[potassium channel inhibitor activity] GO:0019901[protein kinase binding] GO:0019902[phosphatase binding] GO:0030295[protein kinase activator activity] GO:0033633[negative regulation of cell-cell adhesion mediated by integrin] GO:0034115[negative regulation of heterotypic cell-cell adhesion] GO:0034260[negative regulation of GTPase activity] GO:0035556[intracellular signal transduction] GO:0038116[chemokine (C-C motif) ligand 21 signaling pathway] GO:0048666[neuron development] GO:0050801[ion homeostasis] GO:0050852[T cell receptor signaling pathway] GO:0055080[cation homeostasis] GO:0090263[positive regulation of canonical Wnt signaling pathway] GO:0097022[lymphocyte migration into lymph node] GO:0106310[protein serine kinase activity] GO:1903038[negative regulation of leukocyte cell-cell adhesion] GO:1903288[positive regulation of potassium ion import across plasma membrane] GO:1904062[regulation of cation transmembrane transport] GO:1990869[cellular response to chemokine] GO:2000651[positive regulation of sodium ion transmembrane transporter activity]
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
Enzymes ENZYME proteins Transferases Kinases MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins Disease related genes Potential drug targets Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0002028[regulation of sodium ion transport] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004860[protein kinase inhibitor activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006811[ion transport] GO:0007165[signal transduction] GO:0010766[negative regulation of sodium ion transport] GO:0010820[positive regulation of T cell chemotaxis] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0018107[peptidyl-threonine phosphorylation] GO:0019869[chloride channel inhibitor activity] GO:0019870[potassium channel inhibitor activity] GO:0019901[protein kinase binding] GO:0019902[phosphatase binding] GO:0030295[protein kinase activator activity] GO:0033633[negative regulation of cell-cell adhesion mediated by integrin] GO:0034115[negative regulation of heterotypic cell-cell adhesion] GO:0034260[negative regulation of GTPase activity] GO:0035556[intracellular signal transduction] GO:0038116[chemokine (C-C motif) ligand 21 signaling pathway] GO:0048666[neuron development] GO:0050801[ion homeostasis] GO:0050852[T cell receptor signaling pathway] GO:0055080[cation homeostasis] GO:0090263[positive regulation of canonical Wnt signaling pathway] GO:0097022[lymphocyte migration into lymph node] GO:0106310[protein serine kinase activity] GO:1903038[negative regulation of leukocyte cell-cell adhesion] GO:1903288[positive regulation of potassium ion import across plasma membrane] GO:1904062[regulation of cation transmembrane transport] GO:1990869[cellular response to chemokine] GO:2000651[positive regulation of sodium ion transmembrane transporter activity]
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
F5GWT4 [Direct mapping] Non-specific serine/threonine protein kinase
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MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
Enzymes ENZYME proteins Transferases Kinases MEMSAT-SVM predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins Disease related genes Potential drug targets Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166[nucleotide binding] GO:0002028[regulation of sodium ion transport] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004860[protein kinase inhibitor activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006811[ion transport] GO:0007165[signal transduction] GO:0010766[negative regulation of sodium ion transport] GO:0010820[positive regulation of T cell chemotaxis] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0018107[peptidyl-threonine phosphorylation] GO:0019869[chloride channel inhibitor activity] GO:0019870[potassium channel inhibitor activity] GO:0019901[protein kinase binding] GO:0019902[phosphatase binding] GO:0030295[protein kinase activator activity] GO:0033633[negative regulation of cell-cell adhesion mediated by integrin] GO:0034115[negative regulation of heterotypic cell-cell adhesion] GO:0034260[negative regulation of GTPase activity] GO:0035556[intracellular signal transduction] GO:0038116[chemokine (C-C motif) ligand 21 signaling pathway] GO:0048666[neuron development] GO:0050801[ion homeostasis] GO:0050852[T cell receptor signaling pathway] GO:0055080[cation homeostasis] GO:0090263[positive regulation of canonical Wnt signaling pathway] GO:0097022[lymphocyte migration into lymph node] GO:0106310[protein serine kinase activity] GO:1903038[negative regulation of leukocyte cell-cell adhesion] GO:1903288[positive regulation of potassium ion import across plasma membrane] GO:1904062[regulation of cation transmembrane transport] GO:1990869[cellular response to chemokine] GO:2000651[positive regulation of sodium ion transmembrane transporter activity]
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
Enzymes ENZYME proteins Transferases Kinases Phobius predicted secreted proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Plasma proteins Disease related genes Potential drug targets Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000166[nucleotide binding] GO:0002028[regulation of sodium ion transport] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0004860[protein kinase inhibitor activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006811[ion transport] GO:0007165[signal transduction] GO:0010766[negative regulation of sodium ion transport] GO:0010820[positive regulation of T cell chemotaxis] GO:0016020[membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0018107[peptidyl-threonine phosphorylation] GO:0019869[chloride channel inhibitor activity] GO:0019870[potassium channel inhibitor activity] GO:0019901[protein kinase binding] GO:0019902[phosphatase binding] GO:0030295[protein kinase activator activity] GO:0033633[negative regulation of cell-cell adhesion mediated by integrin] GO:0034115[negative regulation of heterotypic cell-cell adhesion] GO:0034260[negative regulation of GTPase activity] GO:0035556[intracellular signal transduction] GO:0038116[chemokine (C-C motif) ligand 21 signaling pathway] GO:0048666[neuron development] GO:0050801[ion homeostasis] GO:0050852[T cell receptor signaling pathway] GO:0055080[cation homeostasis] GO:0090263[positive regulation of canonical Wnt signaling pathway] GO:0097022[lymphocyte migration into lymph node] GO:0106310[protein serine kinase activity] GO:1903038[negative regulation of leukocyte cell-cell adhesion] GO:1903288[positive regulation of potassium ion import across plasma membrane] GO:1904062[regulation of cation transmembrane transport] GO:1990869[cellular response to chemokine] GO:2000651[positive regulation of sodium ion transmembrane transporter activity]
Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC Human disease related genes Nervous system diseases Other nervous and sensory system diseases Urinary system diseases Kidney diseases Protein evidence (Ezkurdia et al 2014)
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