| + |
WNK1 | up-regulates 
phosphorylation
|
OXSR1 |
0.485 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151659 |
Ser325 |
VRRVPGSsGRLHKTE |
Homo sapiens |
|
| pmid |
sentence |
| 17190791 |
Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151663 |
Thr185 |
TRNKVRKtFVGTPCW |
Homo sapiens |
|
| pmid |
sentence |
| 17190791 |
Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1) |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
WNK1 | up-regulates
phosphorylation
|
STK39 |
0.447 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253553 |
Ser371 |
VRRVPGSsGHLHKTE |
Homo sapiens |
|
| pmid |
sentence |
| 16083423 |
Phosphorylation by WNK1 or WNK4 markedly increased SPAK and OSR1 activity. Phosphopeptide mapping studies demonstrated that WNK1 phosphorylated kinase-inactive SPAK and OSR1 at an equivalent residue located within the T-loop of the catalytic domain (Thr233 in SPAK, Thr185 in OSR1) and a serine residue located within a C-terminal non-catalytic region (Ser373 in SPAK, Ser325 in OSR1) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160842 |
Ser371 |
VRRVPGSsGHLHKTE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18270262 |
Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151667 |
Ser371 |
VRRVPGSsGHLHKTE |
Homo sapiens |
|
| pmid |
sentence |
| 17190791 |
Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160846 |
Thr231 |
TRNKVRKtFVGTPCW |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16083423 |
Phosphorylation by WNK1 or WNK4 markedly increased SPAK and OSR1 activity. Phosphopeptide mapping studies demonstrated that WNK1 phosphorylated kinase-inactive SPAK and OSR1 at an equivalent residue located within the T-loop of the catalytic domain (Thr233 in SPAK, Thr185 in OSR1) and a serine residue located within a C-terminal non-catalytic region (Ser373 in SPAK, Ser325 in OSR1) |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151671 |
Thr231 |
TRNKVRKtFVGTPCW |
Homo sapiens |
|
| pmid |
sentence |
| 17190791 |
Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1). |
|
| Publications: |
5 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| + |
WNK3 | up-regulates activity
phosphorylation
|
WNK1 |
0.282 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260789 |
Ser382 |
KRASFAKsVIGTPEF |
Homo sapiens |
|
| pmid |
sentence |
| 22032326 |
We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | up-regulates
phosphorylation
|
WNK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-151675 |
Ser382 |
KRASFAKsVIGTPEF |
Homo sapiens |
|
| pmid |
sentence |
| 17190791 |
We finally establish that full-length wnk1, wnk2 and wnk3, but not wnk4, are capable of directly phosphorylating ser382 of wnk1 in vitro. This supports the notion that t-loop phosphorylation of wnk isoforms is controlled by trans-autophosphorylation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-160850 |
Ser382 |
KRASFAKsVIGTPEF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18270262 |
We demonstrate that wnk1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its t-loop ser382 residue, possibly triggered by a transautophosphorylation reaction. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Kidney |
| + |
WNK2 | up-regulates activity
phosphorylation
|
WNK1 |
0.547 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260790 |
Ser382 |
KRASFAKsVIGTPEF |
Homo sapiens |
|
| pmid |
sentence |
| 22032326 |
WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | up-regulates activity
phosphorylation
|
WNK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260826 |
Ser382 |
LKRASFAkSVIGTPE |
Homo sapiens |
|
| pmid |
sentence |
| 12374799 |
Activation of WNKs requires autophosphorylation of at least one serine residue, serine 382 in WNK1, within the WNK activation loop. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | up-regulates activity
phosphorylation
|
SLC12A2 |
0.491 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277859 |
Thr1023 |
QKKQGKNtIDVWWLF |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 36318922 |
Combining these biochemical studies with the live cell imaging data, these results collectively suggest that the entire CTD is necessary for WNK1 to drive optimal SPAK/OSR1 activation and downstream NKCC1/KCC phosphorylation via PS. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | down-regulates 
phosphorylation
|
SLC12A6 |
0.453 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-187560 |
Thr1048 |
YQEKVHMtWTKDKYM |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19665974 |
We have attempted to identify kinases and phosphatases involved in the modulation of phosphorylation at kcc3 t991 and t1048. the wnk kinases and spak/osr1 are strong candidates for kcc3 regulatory kinases. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-187564 |
Thr991 |
SAYTYERtLMMEQRS |
Homo sapiens |
Neuron |
| pmid |
sentence |
| 19665974 |
We have attempted to identify kinases and phosphatases involved in the modulation of phosphorylation at kcc3 t991 and t1048. the wnk kinases and spak/osr1 are strong candidates for kcc3 regulatory kinases. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
WNK1 | up-regulates activity
phosphorylation
|
SYT2 |
0.603 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263049 |
Thr199 |
ETKVHRKtLNPAFNE |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 15350218 |
Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. . In contrast, WNK1 phosphorylated Syt2 on T202 and T386 within the C2 domains (Figure 6B). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT1 | up-regulates
phosphorylation
|
WNK1 |
0.394 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252481 |
Thr60 |
EYRRRRHtMDKDSRG |
Homo sapiens |
|
| pmid |
sentence |
| 16081417 |
Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
AKT | up-regulates
phosphorylation
|
WNK1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-139391 |
Thr60 |
EYRRRRHtMDKDSRG |
Homo sapiens |
|
| pmid |
sentence |
| 16081417 |
Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KLHL3 | down-regulates quantity by destabilization
binding
|
WNK1 |
0.563 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272099 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 23387299 |
CUL3 assembles with BTB proteins to form Cullin-RING E3 ubiquitin ligase complexes. To explore how a CUL3-KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3. These results suggest that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to interact with and ubiquitylate WNK isoforms. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Cullin 3-RBX1-Skp1 | down-regulates quantity by destabilization
polyubiquitination, ubiquitination
|
WNK1 |
0.321 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272124 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272100 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 23387299 |
CUL3 assembles with BTB proteins to form Cullin-RING E3 ubiquitin ligase complexes. To explore how a CUL3-KLHL3 complex might operate, we immunoprecipitated KLHL3 and found that it associated strongly with WNK isoforms and CUL3. These results suggest that the CUL3-KLHL3 E3 ligase complex regulates blood pressure via its ability to interact with and ubiquitylate WNK isoforms. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
KLHL2 | down-regulates quantity by destabilization
binding
|
WNK1 |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272119 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 23838290 |
We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | down-regulates activity
phosphorylation
|
SLC12A5 |
0.461 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-280163 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23300475 |
The activity of the neuronal specific KCC2 had recently been shown to be regulated by the WNK1 kinase, where phosphorylation decreased KCC2 activation .|WNK1 phosphorylation of KCC2 occurs in immature neurons but is absent in adult neurons , , emphasizing a developmental role. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
WNK1 | up-regulates quantity
phosphorylation
|
SMAD2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-280164 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28236964 |
In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
WNK1
- 
- 