STRINGSTRING
STRING protein interaction network
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
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Wnk4Serine/threonine-protein kinase WNK4; 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 SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-in [...] (1222 aa)    
Predicted Functional Partners:
Klhl3
Kelch-like protein 3; Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (By similarity). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity).
    
 
 0.942
Kcnj1
ATP-sensitive inward rectifier potassium channel 1; In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal A [...]
    
 
 0.844
Slc12a3
Solute carrier family 12 member 3; Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption. Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2, either independently of IL18R1, or as a complex with IL18R1 (By similarity).
    
 
 0.822
Slc12a1
Solute carrier family 12 member 1; Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation. Electrically silent transporter system.
    
 
 0.797
Scnn1g
Amiloride-sensitive sodium channel subunit gamma; Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
      
 0.783
Slc12a2
Solute carrier family 12 member 2.
    
 
 0.756
Cul3
Cullin-3; Core component of multiple cullin-RING-based BCR (BTB-CUL3- RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (By similarity). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin- protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the [...]
    
 
 0.754
Klhl2
Kelch-like protein 2; Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation. Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4 (By similarity). Promotes growth of cell projections in oligodendrocyte precursors. Plays a role in the reorganization of the actin cytoskeleton.
    
 
 0.725
Stk39
STE20/SPS1-related proline-alanine-rich protein kinase; May act as a mediator of stress-activated signals. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation. Phosphorylates RELT.
    
 
0.723
Trpv5
Transient receptor potential cation channel subfamily V member 5; Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine. Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (By similarity). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. [...]
   
 
 0.709
Your Current Organism:
Rattus norvegicus
NCBI taxonomy Id: 10116
Other names: Buffalo rat, Norway rat, R. norvegicus, Rattus PC12 clone IS, Rattus sp. strain Wistar, Sprague-Dawley rat, Wistar rats, brown rat, laboratory rat, rat, rats, zitter rats
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