Relation Results

Summary

Name SLC12A3
Full Name Solute carrier family 12 member 3
Synonyms Na-Cl cotransporter, NCC, Na-Cl symporter, Thiazide-sensitive sodium-chloride cotransporter | NCC, TSC
Primary ID P55017
Links - -
Type protein
Relations 6
Function Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21 ...
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Type: Score: Layout: SPV 
0.5840.4880.390.4580.8WNK4SLC12A3STK39OXSR1WNK3chloride

Modifications Tables

Relations

Regulator
Mechanism
target
score
+ up-regulates activity img/direct-activation.png phosphorylation SLC12A3 0.584
Identifier Residue Sequence Organism Cell Line
SIGNOR-264631 Thr50 SHLTHSStFCMRTFG in vitro
pmid sentence
Threonine 48 was identified as the WNK4 phosphorylation site at mouse NCC|. Thus, WNK4 stimulates NCC in three ways: (1) direct phosphorylation and in turn increasing NCC protein abundance; (2) facilitating the phosphorylation of NCC by SPAK/OSR1 indirectly, and (3) phosphorylating and activating SPAK/OSR1.|Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation SLC12A3 0.488
Identifier Residue Sequence Organism Cell Line
SIGNOR-264623 Thr55 SSTFCMRtFGYNTID Mus musculus
pmid sentence
SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface| the kinase (SPAK) that phosphorylates NCC at T53
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation SLC12A3 0.39
Identifier Residue Sequence Organism Cell Line
SIGNOR-160833 Thr60 MRTFGYNtIDVVPTY Homo sapiens HEK-293 Cell
pmid sentence
We demonstrate that the spak and osr1 kinases that are activated by wnk1 phosphorylate human ncc at three conserved residues (thr46, thr55 and thr60) / our results also indicate that phosphorylation of thr60 plays the most crucial role in triggering the activation of ncc in hek293 cells and its mutation also inhibits phosphorylation of the adjacent thr46 and thr55 sites.
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates activity img/direct-activation.png phosphorylation SLC12A3 0.458
Identifier Residue Sequence Organism Cell Line
SIGNOR-264624
pmid sentence
We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs
Publications: 1
+ up-regulates quantity img/direct-activation.png phosphorylation chloride 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-264633
pmid sentence
Eukaryotic cells regulate their volume in the long term through the coordinated function of the Na+-coupled chloride (NKCC1/2 and NCC) and K+-coupled chloride (KCC1–4) cotransporters, which encompass two branches of the SLC12|The K+-Cl− cotransporters move chloride outside the cell, are inhibited by phosphorylation, and are activated by dephosphorylation. In contrast, the Na+-K+-2Cl− cotransporters introduce chloride into the cell, are inhibited by dephosphorylation, and are activated by phosphorylation gene family of solute transporters (12). 
Publications: 1
+ down-regulates activity img/indirect_inhibition.png SLC12A3 0.584
Identifier Residue Sequence Organism Cell Line
SIGNOR-264632
pmid sentence
Evidences from early studies using Xenopus oocytes and mammalian cells indicate that WNK4 inhibits NCC and PHAII-causing mutations relieve the inhibition
Publications: 1
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