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Protein

Serine/threonine-protein kinase WNK4

Gene

WNK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K+ secretion to maintain integrated homeostasis. Phosphorylates NEDD4L. Acts as a scaffold to inhibit SLC4A4 as well as CFTR activities and surface expression, recruits STK39 which mediates the inhibition (By similarity).By similarity1 Publication

Caution

Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes increased activity (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei184ATP; via amide nitrogenBy similarity1
Binding sitei304ATPBy similarity1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei321Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi254 – 257ATPBy similarity4

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • chloride channel inhibitor activity Source: UniProtKB
  • potassium channel inhibitor activity Source: GO_Central
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-2672351 Stimuli-sensing channels

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
Q96J92

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Serine/threonine-protein kinase WNK4Curated (EC:2.7.11.1By similarity)
Alternative name(s):
Protein kinase lysine-deficient 4Imported
Protein kinase with no lysine 41 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:WNK4Imported
Synonyms:PRKWNK4Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 17

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000126562.16

Human Gene Nomenclature Database

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HGNCi
HGNC:14544 WNK4

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
601844 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q96J92

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Tight junction

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Pseudohypoaldosteronism 2B (PHA2B)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.
See also OMIM:614491
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_017588562E → K in PHA2B; impaired interaction with KLHL3. 3 PublicationsCorresponds to variant dbSNP:rs137853093EnsemblClinVar.1
Natural variantiVAR_017589564D → A in PHA2B; impaired interaction with KLHL3. 2 PublicationsCorresponds to variant dbSNP:rs137853094EnsemblClinVar.1
Natural variantiVAR_017590565Q → E in PHA2B; impaired interaction with KLHL3. 3 PublicationsCorresponds to variant dbSNP:rs137853092EnsemblClinVar.1
Natural variantiVAR_0175911185R → C in PHA2B. 1 PublicationCorresponds to variant dbSNP:rs137853095EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
65266

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
WNK4

MalaCards human disease database

More...
MalaCardsi
WNK4
MIMi614491 phenotype

Open Targets

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OpenTargetsi
ENSG00000126562

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
88939 Pseudohypoaldosteronism type 2B

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA134875400

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1795196

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
WNK4

Domain mapping of disease mutations (DMDM)

More...
DMDMi
41688789

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000868241 – 1243Serine/threonine-protein kinase WNK4Add BLAST1243

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei97PhosphoserineCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki186Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki328Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei331Phosphoserine; by autocatalysisBy similarity1
Modified residuei335Phosphoserine; by autocatalysisBy similarity1
Cross-linki387Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki393Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki450Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki454Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1010Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei1035PhosphoserineBy similarity1
Cross-linki1144Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki1158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei1217PhosphoserineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated by WNK1 and WNK3.By similarity
Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation and increased expression of KCNJ1 at the cell surface. Ubiquitinated by the BCR(KLHL2) complex.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q96J92

MaxQB - The MaxQuant DataBase

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MaxQBi
Q96J92

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q96J92

PeptideAtlas

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PeptideAtlasi
Q96J92

PRoteomics IDEntifications database

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PRIDEi
Q96J92

ProteomicsDB human proteome resource

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ProteomicsDBi
76909
76910 [Q96J92-2]
76911 [Q96J92-3]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q96J92

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q96J92

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in kidney, colon and skin.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000126562 Expressed in 106 organ(s), highest expression level in cortex of kidney

CleanEx database of gene expression profiles

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CleanExi
HS_WNK4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q96J92 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q96J92 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA016500

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity). Interacts with KLHL3 (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:26435498, PubMed:27727489).By similarity6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
OXSR1O9574711EBI-766352,EBI-620853

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
122421, 10 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q96J92

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q96J92

Protein interaction database and analysis system

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IntActi
Q96J92, 6 interactors

Molecular INTeraction database

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MINTi
Q96J92

STRING: functional protein association networks

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STRINGi
9606.ENSP00000246914

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q96J92

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q96J92

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q96J92

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini174 – 432Protein kinasePROSITE-ProRule annotationAdd BLAST259

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.PROSITE-ProRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0584 Eukaryota
ENOG410XQWZ LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159871

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000230962

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG050347

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q96J92

KEGG Orthology (KO)

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KOi
K08867

Identification of Orthologs from Complete Genome Data

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OMAi
LEHRSWA

Database of Orthologous Groups

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OrthoDBi
EOG091G06LL

Database for complete collections of gene phylogenies

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PhylomeDBi
Q96J92

TreeFam database of animal gene trees

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TreeFami
TF315363

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024678 Kinase_OSR1/WNK_CCT
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF12202 OSR1_C, 1 hit
PF00069 Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1Curated1 Publication (identifier: Q96J92-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLASPATETT VLMSQTEADL ALRPPPPLGT AGQPRLGPPP RRARRFSGKA
60 70 80 90 100
EPRPRSSRLS RRSSVDLGLL SSWSLPASPA PDPPDPPDSA GPGPARSPPP
110 120 130 140 150
SSKEPPEGTW TEGAPVKAAE DSARPELPDS AVGPGSREPL RVPEAVALER
160 170 180 190 200
RREQEEKEDM ETQAVATSPD GRYLKFDIEI GRGSFKTVYR GLDTDTTVEV
210 220 230 240 250
AWCELQTRKL SRAERQRFSE EVEMLKGLQH PNIVRFYDSW KSVLRGQVCI
260 270 280 290 300
VLVTELMTSG TLKTYLRRFR EMKPRVLQRW SRQILRGLHF LHSRVPPILH
310 320 330 340 350
RDLKCDNVFI TGPTGSVKIG DLGLATLKRA SFAKSVIGTP EFMAPEMYEE
360 370 380 390 400
KYDEAVDVYA FGMCMLEMAT SEYPYSECQN AAQIYRKVTS GRKPNSFHKV
410 420 430 440 450
KIPEVKEIIE GCIRTDKNER FTIQDLLAHA FFREERGVHV ELAEEDDGEK
460 470 480 490 500
PGLKLWLRME DARRGGRPRD NQAIEFLFQL GRDAAEEVAQ EMVALGLVCE
510 520 530 540 550
ADYQPVARAV RERVAAIQRK REKLRKAREL EALPPEPGPP PATVPMAPGP
560 570 580 590 600
PSVFPPEPEE PEADQHQPFL FRHASYSSTT SDCETDGYLS SSGFLDASDP
610 620 630 640 650
ALQPPGGVPS SLAESHLCLP SAFALSIPRS GPGSDFSPGD SYASDAASGL
660 670 680 690 700
SDVGEGMGQM RRPPGRNLRR RPRSRLRVTS VSDQNDRVVE CQLQTHNSKM
710 720 730 740 750
VTFRFDLDGD SPEEIAAAMV YNEFILPSER DGFLRRIREI IQRVETLLKR
760 770 780 790 800
DTGPMEAAED TLSPQEEPAP LPALPVPLPD PSNEELQSST SLEHRSWTAF
810 820 830 840 850
STSSSSPGTP LSPGNPFSPG TPISPGPIFP ITSPPCHPSP SPFSPISSQV
860 870 880 890 900
SSNPSPHPTS SPLPFSSSTP EFPVPLSQCP WSSLPTTSPP TFSPTCSQVT
910 920 930 940 950
LSSPFFPPCP STSSFPSTTA APLLSLASAF SLAVMTVAQS LLSPSPGLLS
960 970 980 990 1000
QSPPAPPSPL PSLPLPPPVA PGGQESPSPH TAEVESEASP PPARPLPGEA
1010 1020 1030 1040 1050
RLAPISEEGK PQLVGRFQVT SSKEPAEPLP LQPTSPTLSG SPKPSTPQLT
1060 1070 1080 1090 1100
SESSDTEDSA GGGPETREAL AESDRAAEGL GAGVEEEGDD GKEPQVGGSP
1110 1120 1130 1140 1150
QPLSHPSPVW MNYSYSSLCL SSEESESSGE DEEFWAELQS LRQKHLSEVE
1160 1170 1180 1190 1200
TLQTLQKKEI EDLYSRLGKQ PPPGIVAPAA MLSSRQRRLS KGSFPTSRRN
1210 1220 1230 1240
SLQRSEPPGP GIMRRNSLSG SSTGSQEQRA SKGVTFAGDV GRM
Length:1,243
Mass (Da):134,739
Last modified:December 1, 2001 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iBAC35F0098BA3391
GO
Isoform 2Curated (identifier: Q96J92-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-228: Missing.
     229-264: QHPNIVRFYDSWKSVLRGQVCIVLVTELMTSGTLKT → MRRRQQGAAGGNFPVGGSFPEDVSPHQDSGYAPSPR
     828-1210: Missing.
     1233-1243: GVTFAGDVGRM → EAGQRPGKLWLRATVQLRVWGLELRRKEMMGRNPKLGAAPNP

Note: No experimental confirmation available.Curated
Show »
Length:663
Mass (Da):73,370
Checksum:i6711A9D6CEFD8146
GO
Isoform 3Curated (identifier: Q96J92-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1145-1165: HLSEVETLQTLQKKEIEDLYS → PFHALRASSGTCQRWKHYRHY
     1166-1243: Missing.

Note: No experimental confirmation available. Incomplete sequence.Curated
Show »
Length:1,165
Mass (Da):126,577
Checksum:i87D926F2D3141A1B
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ENT7K7ENT7_HUMAN
Serine/threonine-protein kinase WNK...
WNK4
469Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
K7EPB3K7EPB3_HUMAN
Serine/threonine-protein kinase WNK...
WNK4
62Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAC04669 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAC48387 differs from that shown. Reason: Frameshift at position 4.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti525R → C in BAC04688 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041330434E → D in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_017588562E → K in PHA2B; impaired interaction with KLHL3. 3 PublicationsCorresponds to variant dbSNP:rs137853093EnsemblClinVar.1
Natural variantiVAR_017589564D → A in PHA2B; impaired interaction with KLHL3. 2 PublicationsCorresponds to variant dbSNP:rs137853094EnsemblClinVar.1
Natural variantiVAR_017590565Q → E in PHA2B; impaired interaction with KLHL3. 3 PublicationsCorresponds to variant dbSNP:rs137853092EnsemblClinVar.1
Natural variantiVAR_061748601A → S. Corresponds to variant dbSNP:rs55781437EnsemblClinVar.1
Natural variantiVAR_051685677R → W. Corresponds to variant dbSNP:rs9896991Ensembl.1
Natural variantiVAR_041331813P → L1 Publication1
Natural variantiVAR_051686961P → S. Corresponds to variant dbSNP:rs2290041EnsemblClinVar.1
Natural variantiVAR_041332992P → S in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0413331013L → P1 Publication1
Natural variantiVAR_0175911185R → C in PHA2B. 1 PublicationCorresponds to variant dbSNP:rs137853095EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0506481 – 228Missing in isoform 2. 1 PublicationAdd BLAST228
Alternative sequenceiVSP_050649229 – 264QHPNI…GTLKT → MRRRQQGAAGGNFPVGGSFP EDVSPHQDSGYAPSPR in isoform 2. 1 PublicationAdd BLAST36
Alternative sequenceiVSP_050650828 – 1210Missing in isoform 2. 1 PublicationAdd BLAST383
Alternative sequenceiVSP_0506521145 – 1165HLSEV…EDLYS → PFHALRASSGTCQRWKHYRH Y in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_0506531166 – 1243Missing in isoform 3. 1 PublicationAdd BLAST78
Alternative sequenceiVSP_0506511233 – 1243GVTFAGDVGRM → EAGQRPGKLWLRATVQLRVW GLELRRKEMMGRNPKLGAAP NP in isoform 2. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF390018 mRNA Translation: AAK91995.1
AJ316534 mRNA Translation: CAC48387.1 Frameshift.
AK096003 mRNA Translation: BAC04669.1 Different initiation.
AK096052 mRNA Translation: BAC04688.1
EU332870 Genomic DNA Translation: ABY87559.1
CH471152 Genomic DNA Translation: EAW60881.1
CH471152 Genomic DNA Translation: EAW60882.1
BC136664 mRNA Translation: AAI36665.1
AJ309861 mRNA Translation: CAC32991.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS11439.1 [Q96J92-1]

NCBI Reference Sequences

More...
RefSeqi
NP_115763.2, NM_032387.4 [Q96J92-1]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.105448

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000246914; ENSP00000246914; ENSG00000126562 [Q96J92-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
65266

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:65266

UCSC genome browser

More...
UCSCi
uc002ibj.4 human [Q96J92-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF390018 mRNA Translation: AAK91995.1
AJ316534 mRNA Translation: CAC48387.1 Frameshift.
AK096003 mRNA Translation: BAC04669.1 Different initiation.
AK096052 mRNA Translation: BAC04688.1
EU332870 Genomic DNA Translation: ABY87559.1
CH471152 Genomic DNA Translation: EAW60881.1
CH471152 Genomic DNA Translation: EAW60882.1
BC136664 mRNA Translation: AAI36665.1
AJ309861 mRNA Translation: CAC32991.1
CCDSiCCDS11439.1 [Q96J92-1]
RefSeqiNP_115763.2, NM_032387.4 [Q96J92-1]
UniGeneiHs.105448

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V3SX-ray1.70C/D1015-1020[»]
4CH9X-ray1.84C/D557-567[»]
4CHBX-ray1.56C/D557-567[»]
ProteinModelPortaliQ96J92
SMRiQ96J92
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122421, 10 interactors
CORUMiQ96J92
ELMiQ96J92
IntActiQ96J92, 6 interactors
MINTiQ96J92
STRINGi9606.ENSP00000246914

Chemistry databases

ChEMBLiCHEMBL1795196

PTM databases

iPTMnetiQ96J92
PhosphoSitePlusiQ96J92

Polymorphism and mutation databases

BioMutaiWNK4
DMDMi41688789

Proteomic databases

EPDiQ96J92
MaxQBiQ96J92
PaxDbiQ96J92
PeptideAtlasiQ96J92
PRIDEiQ96J92
ProteomicsDBi76909
76910 [Q96J92-2]
76911 [Q96J92-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246914; ENSP00000246914; ENSG00000126562 [Q96J92-1]
GeneIDi65266
KEGGihsa:65266
UCSCiuc002ibj.4 human [Q96J92-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
65266
DisGeNETi65266
EuPathDBiHostDB:ENSG00000126562.16

GeneCards: human genes, protein and diseases

More...
GeneCardsi
WNK4
GeneReviewsiWNK4
HGNCiHGNC:14544 WNK4
HPAiHPA016500
MalaCardsiWNK4
MIMi601844 gene
614491 phenotype
neXtProtiNX_Q96J92
OpenTargetsiENSG00000126562
Orphaneti88939 Pseudohypoaldosteronism type 2B
PharmGKBiPA134875400

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0584 Eukaryota
ENOG410XQWZ LUCA
GeneTreeiENSGT00940000159871
HOGENOMiHOG000230962
HOVERGENiHBG050347
InParanoidiQ96J92
KOiK08867
OMAiLEHRSWA
OrthoDBiEOG091G06LL
PhylomeDBiQ96J92
TreeFamiTF315363

Enzyme and pathway databases

ReactomeiR-HSA-2672351 Stimuli-sensing channels
SignaLinkiQ96J92

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
WNK4 human
EvolutionaryTraceiQ96J92

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
WNK4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
65266

Protein Ontology

More...
PROi
PR:Q96J92

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000126562 Expressed in 106 organ(s), highest expression level in cortex of kidney
CleanExiHS_WNK4
ExpressionAtlasiQ96J92 baseline and differential
GenevisibleiQ96J92 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024678 Kinase_OSR1/WNK_CCT
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF12202 OSR1_C, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiWNK4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q96J92
Secondary accession number(s): B0LPI0
, Q8N8X3, Q8N8Z2, Q96DT8, Q9BYS5
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 2, 2004
Last sequence update: December 1, 2001
Last modified: December 5, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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