Protein: Q9H4A3

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
Q9H4A3 (Uniprot) WNK1_HUMAN WNK1 Serine/threonine-protein kinase WNK1 human No
Uniprot: 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).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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0007165 signal transduction 4, 187, 282 GO:0006725 cellular aromatic compound metabolic process 484 5.44e-126 5.27e-27
GO:0034641 cellular nitrogen compound metabolic process 35 GO:0007165 signal transduction 4, 512 4.22e-144 6.90e-18
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
2 GO:0044267 cellular protein metabolic process
2 GO:0010467 gene expression
2 GO:0006139 nucleobase-containing compound metabolic process
2 GO:0060255 regulation of macromolecule metabolic process
2 GO:0007165 signal transduction
4 GO:0035556 intracellular signal transduction
4 GO:0031399 regulation of protein modification process
4 GO:0009966 regulation of signal transduction
7 GO:0031324 negative regulation of cellular metabolic process
7 GO:0010605 negative regulation of macromolecule metabolic process
7 GO:0051172 negative regulation of nitrogen compound metabolic process
7 GO:0010604 positive regulation of macromolecule metabolic process
7 GO:0006357 regulation of transcription from RNA polymerase II promoter
35 GO:0044271 cellular nitrogen compound biosynthetic process
35 GO:0044267 cellular protein metabolic process
35 GO:0090304 nucleic acid metabolic process
35 GO:0010468 regulation of gene expression
35 GO:0009966 regulation of signal transduction
118 GO:0019538 protein metabolic process
118 GO:0060255 regulation of macromolecule metabolic process
118 GO:0007165 signal transduction
172 GO:0060255 regulation of macromolecule metabolic process
187 GO:0007166 cell surface receptor signaling pathway
187 GO:0006464 cellular protein modification process
187 GO:0070887 cellular response to chemical stimulus
187 GO:0035556 intracellular signal transduction
187 GO:0006928 movement of cell or subcellular component
187 GO:0006796 phosphate-containing compound metabolic process
187 GO:0010647 positive regulation of cell communication
187 GO:0048584 positive regulation of response to stimulus
187 GO:0023056 positive regulation of signaling
187 GO:0060255 regulation of macromolecule metabolic process
187 GO:0009966 regulation of signal transduction
275 GO:0022607 cellular component assembly
275 GO:0006796 phosphate-containing compound metabolic process
275 GO:0060255 regulation of macromolecule metabolic process
275 GO:0007165 signal transduction
282 GO:0035556 intracellular signal transduction
282 GO:0043085 positive regulation of catalytic activity
282 GO:0031325 positive regulation of cellular metabolic process
282 GO:0051173 positive regulation of nitrogen compound metabolic process
282 GO:0060255 regulation of macromolecule metabolic process
282 GO:0019220 regulation of phosphate metabolic process
310 GO:0019538 protein metabolic process
371 GO:0016070 RNA metabolic process
371 GO:0034645 cellular macromolecule biosynthetic process
371 GO:0044271 cellular nitrogen compound biosynthetic process
371 GO:0010468 regulation of gene expression
471 GO:0034645 cellular macromolecule biosynthetic process
471 GO:0044271 cellular nitrogen compound biosynthetic process
471 GO:0006464 cellular protein modification process
471 GO:0031324 negative regulation of cellular metabolic process
471 GO:0010605 negative regulation of macromolecule metabolic process
471 GO:0010604 positive regulation of macromolecule metabolic process
471 GO:0051173 positive regulation of nitrogen compound metabolic process
471 GO:0051252 regulation of RNA metabolic process
471 GO:0010468 regulation of gene expression
471 GO:0007165 signal transduction
484 GO:0006139 nucleobase-containing compound metabolic process
484 GO:1901362 organic cyclic compound biosynthetic process
484 GO:0019538 protein metabolic process
484 GO:0060255 regulation of macromolecule metabolic process
484 GO:0007165 signal transduction
512 GO:0035556 intracellular signal transduction
512 GO:0006468 protein phosphorylation
512 GO:0060255 regulation of macromolecule metabolic process
513 GO:0007165 signal transduction
549 GO:0008219 cell death
549 GO:0070887 cellular response to chemical stimulus
549 GO:0033554 cellular response to stress
549 GO:0035556 intracellular signal transduction
549 GO:0031325 positive regulation of cellular metabolic process
549 GO:0010604 positive regulation of macromolecule metabolic process
549 GO:0051173 positive regulation of nitrogen compound metabolic process
549 GO:0048584 positive regulation of response to stimulus
549 GO:0006468 protein phosphorylation
549 GO:0051252 regulation of RNA metabolic process
549 GO:2000112 regulation of cellular macromolecule biosynthetic process
549 GO:0032268 regulation of cellular protein metabolic process
549 GO:0010468 regulation of gene expression
549 GO:0009966 regulation of signal transduction
549 GO:0006351 transcription, DNA-templated
652 GO:0044267 cellular protein metabolic process
652 GO:0060255 regulation of macromolecule metabolic process
696 GO:0022607 cellular component assembly
696 GO:0006464 cellular protein modification process
696 GO:0060255 regulation of macromolecule metabolic process
696 GO:0007165 signal transduction
704 GO:0007165 signal transduction
724 GO:0016070 RNA metabolic process
724 GO:0035556 intracellular signal transduction
724 GO:0009892 negative regulation of metabolic process
724 GO:0034654 nucleobase-containing compound biosynthetic process
724 GO:0006468 protein phosphorylation
724 GO:2000112 regulation of cellular macromolecule biosynthetic process
724 GO:0032268 regulation of cellular protein metabolic process
724 GO:0010468 regulation of gene expression
724 GO:0019219 regulation of nucleobase-containing compound metabolic process
792 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
2 GO:0005829 cytosol
2 GO:0005634 nucleus
4 GO:0005829 cytosol
4 GO:0005634 nucleus
7 GO:0005654 nucleoplasm
11 GO:0005634 nucleus
35 GO:0005829 cytosol
35 GO:0005634 nucleus
35 GO:0005886 plasma membrane
187 GO:0005829 cytosol
187 GO:0005886 plasma membrane
275 GO:0043232 intracellular non-membrane-bounded organelle
275 GO:0005634 nucleus
282 GO:0005829 cytosol
282 GO:0005886 plasma membrane
291 GO:0043232 intracellular non-membrane-bounded organelle
291 GO:0005634 nucleus
310 GO:0005829 cytosol
310 GO:0005634 nucleus
371 GO:0005634 nucleus
471 GO:0005654 nucleoplasm
484 GO:0070013 intracellular organelle lumen
484 GO:0005634 nucleus
501 GO:0031090 organelle membrane
512 GO:0005829 cytosol
513 GO:0005829 cytosol
513 GO:0005634 nucleus
525 GO:0005829 cytosol
549 GO:0005829 cytosol
549 GO:0005634 nucleus
652 GO:0005829 cytosol
652 GO:0005634 nucleus
652 GO:0031982 vesicle
696 GO:0005829 cytosol
696 GO:0043232 intracellular non-membrane-bounded organelle
696 GO:0005634 nucleus
724 GO:0005829 cytosol
724 GO:0070013 intracellular organelle lumen
724 GO:0005634 nucleus
792 GO:0005829 cytosol
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0002028 regulation of sodium ion transport ISS
GO:0003084 positive regulation of systemic arterial blood pressure IEA
GO:0006468 protein phosphorylation IMP
GO:0006811 ion transport ISS
GO:0010923 negative regulation of phosphatase activity IDA
GO:0018107 peptidyl-threonine phosphorylation TAS
GO:0023016 signal transduction by trans-phosphorylation IDA
GO:0032147 activation of protein kinase activity IEA
GO:0035556 intracellular signal transduction TAS
GO:0046777 protein autophosphorylation IEA
GO:0048666 neuron development NAS
GO:0050794 regulation of cellular process ISS
GO:0071277 cellular response to calcium ion IEA
GO:0071901 negative regulation of protein serine/threonine kinase activity IEA
GO:0090188 negative regulation of pancreatic juice secretion IEA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005737 cytoplasm IDA
GO:0005829 cytosol IDA
GO:0016020 membrane ISS
No pairs of PrOnto dissimilar CC GO terms found.
PMID Article Title
2507249 Nucleoplasmic and cytoplasmic glycoproteins.
9205841 Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.
10660600 PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the JNK MAPK pathway and regulates actin cytoskeletal organisation.
11498583 Human hypertension caused by mutations in WNK kinases.
11571656 WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.
12168954 Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.
14645531 Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform.
15060842 Identification of a novel gene (HSN2) causing hereditary sensory and autonomic neuropathy type II through the study of Canadian genetic isolates.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15911806 Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in French Canadians.
16541075 The finished DNA sequence of human chromosome 12.
16959974 The consensus coding sequences of human breast and colorectal cancers.
16964243 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
17081983 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
17344846 Patterns of somatic mutation in human cancer genomes.
18220336 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
18521183 Mutations in the nervous system--specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II.
18669648 A quantitative atlas of mitotic phosphorylation.
19413330 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
22701532 A new methodology for quantification of alternatively spliced exons reveals a highly tissue-specific expression pattern of WNK1 isoforms.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23387299 The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction.
23576762 Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4.
23838290 KLHL2 interacts with and ubiquitinates WNK kinases.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24803536 Chloride sensing by WNK1 involves inhibition of autophosphorylation.
27712055 Discovery and characterization of allosteric WNK kinase inhibitors.
OMIM ID Disease Name
201300 Neuropathy, hereditary sensory and autonomic, 2A
614492 Pseudohypoaldosteronism 2C
Domain Name Domain ID Source
Prot_kinase_dom IPR000719 InterPro
Ser/Thr_kinase_AS IPR008271 InterPro
Kinase-like_dom_sf IPR011009 InterPro
Kinase_OSR1/WNK_CCT IPR024678 InterPro
Pkinase PF00069 Pfam
OSR1_C PF12202 Pfam
PROTEIN_KINASE_ST PS00108 PROSITE
PROTEIN_KINASE_DOM PS50011 PROSITE
S_TKc SM00220 SMART
SSF56112 SSF56112 SUPFAM