Browse WNK1

Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm
Domain PF12202 Oxidative-stress-responsive kinase 1 C terminal
PF00069 Protein kinase domain
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 SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4, SLC26A6 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity). ; FUNCTION: Isoform 3: Dominant-negative regulator of the longer isoform 1. Does not have kinase activity, does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Downregulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity. In kidney, may play an important role regulating sodium and potassium balance.

> Gene Ontology
 
Biological Process GO:0001933 negative regulation of protein phosphorylation
GO:0002028 regulation of sodium ion transport
GO:0003013 circulatory system process
GO:0003073 regulation of systemic arterial blood pressure
GO:0003084 positive regulation of systemic arterial blood pressure
GO:0006469 negative regulation of protein kinase activity
GO:0006814 sodium ion transport
GO:0007586 digestion
GO:0007589 body fluid secretion
GO:0008015 blood circulation
GO:0008217 regulation of blood pressure
GO:0010921 regulation of phosphatase activity
GO:0010923 negative regulation of phosphatase activity
GO:0010959 regulation of metal ion transport
GO:0015672 monovalent inorganic cation transport
GO:0016311 dephosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018210 peptidyl-threonine modification
GO:0022600 digestive system process
GO:0022898 regulation of transmembrane transporter activity
GO:0023016 signal transduction by trans-phosphorylation
GO:0030157 pancreatic juice secretion
GO:0032147 activation of protein kinase activity
GO:0032409 regulation of transporter activity
GO:0032411 positive regulation of transporter activity
GO:0032412 regulation of ion transmembrane transporter activity
GO:0032414 positive regulation of ion transmembrane transporter activity
GO:0032844 regulation of homeostatic process
GO:0032941 secretion by tissue
GO:0033673 negative regulation of kinase activity
GO:0033674 positive regulation of kinase activity
GO:0034762 regulation of transmembrane transport
GO:0034764 positive regulation of transmembrane transport
GO:0034765 regulation of ion transmembrane transport
GO:0034767 positive regulation of ion transmembrane transport
GO:0035303 regulation of dephosphorylation
GO:0035305 negative regulation of dephosphorylation
GO:0042326 negative regulation of phosphorylation
GO:0043270 positive regulation of ion transport
GO:0044057 regulation of system process
GO:0044058 regulation of digestive system process
GO:0045777 positive regulation of blood pressure
GO:0045860 positive regulation of protein kinase activity
GO:0046777 protein autophosphorylation
GO:0050878 regulation of body fluid levels
GO:0051048 negative regulation of secretion
GO:0051051 negative regulation of transport
GO:0051346 negative regulation of hydrolase activity
GO:0051348 negative regulation of transferase activity
GO:0060457 negative regulation of digestive system process
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0090186 regulation of pancreatic juice secretion
GO:0090188 negative regulation of pancreatic juice secretion
GO:2000021 regulation of ion homeostasis
Molecular Function GO:0000287 magnesium ion binding
GO:0004674 protein serine/threonine kinase activity
GO:0004857 enzyme inhibitor activity
GO:0004860 protein kinase inhibitor activity
GO:0008047 enzyme activator activity
GO:0008200 ion channel inhibitor activity
GO:0015459 potassium channel regulator activity
GO:0016247 channel regulator activity
GO:0016248 channel inhibitor activity
GO:0017081 chloride channel regulator activity
GO:0019207 kinase regulator activity
GO:0019209 kinase activator activity
GO:0019210 kinase inhibitor activity
GO:0019869 chloride channel inhibitor activity
GO:0019870 potassium channel inhibitor activity
GO:0019887 protein kinase regulator activity
GO:0019902 phosphatase binding
GO:0030291 protein serine/threonine kinase inhibitor activity
GO:0030295 protein kinase activator activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-983712: Ion channel transport
R-HSA-2672351: Stimuli-sensing channels
R-HSA-382551: Transmembrane transport of small molecules
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between WNK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of WNK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of WNK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0470.834
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2480.902
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2590.856
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1790.527
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1330.966
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2410.953
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.3380.472
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3390.878
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3750.876
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5050.752
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.0680.654
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0960.0794
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of WNK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.18.22.90.699
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.110.20.91
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.2022.20.12
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.93.74.20.636
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.67.75.91
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of WNK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of WNK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by WNK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of WNK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of WNK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between WNK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolWNK1
NameWNK lysine deficient protein kinase 1
Aliases HSAN2; PPP1R167; protein phosphatase 1, regulatory subunit 167; PRKWNK1; HSN2; protein kinase, lysine defici ......
Chromosomal Location12p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting WNK1 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.