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MGP005829

UniProt Annotations

Entry Information
Gene NameWNK lysine deficient protein kinase 1
Protein EntryWNK1_HUMAN
UniProt IDQ9H4A3
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative promoter usage, Alternative splicing; Named isoforms=6; Comment=WNK1 is a complex 33-exons gene, in total 9 WNK1 exons are alternatively spliced, some expressed in a tissue-specific manner. Additional isoforms seems to exist.; Name=1 {ECO:0000269|PubMed:11571656}; Synonyms=L-WNK1; IsoId=Q9H4A3-1; Sequence=Displayed; Note=Strong expression in dorsal root ganglia and spinal cord.; Name=2 {ECO:0000303|PubMed:9205841}; IsoId=Q9H4A3-2; Sequence=VSP_040269, VSP_050638; Note=No experimental confirmation available. {ECO:0000305}; Name=3; Synonyms=KS-WNK1, Kidney-Specific; IsoId=Q9H4A3-4; Sequence=VSP_050634, VSP_050637; Note=Kinase-defective isoform. Produced by alternative promoter usage and alternative splicing.; Name=4; Synonyms=Brain and spinal cord variant; IsoId=Q9H4A3-5; Sequence=VSP_040268; Note=Contains the nervous system-specific exon HSN2. Produced by alternative splicing.; Name=5; Synonyms=Dorsal root ganglia and sciatic nerve variant, DRG and sciatic nerve variant; IsoId=Q9H4A3-6; Sequence=VSP_040267, VSP_040270; Note=Contains the nervous system-specific exon HSN2. Produced by alternative splicing.; Name=6; IsoId=Q9H4A3-7; Sequence=VSP_040267, VSP_053767; Note=Contains the nervous system-specific exon HSN2. Produced by alternative splicing.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CautionCys-250 is present instead of the conserved Lys which is expected to be an active site residue. Lys-233 appears to fulfill the required catalytic function. {ECO:0000250|UniProtKB:Q9JIH7}.
CautionHSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown to be a nervous system-specific exon of WNK1 included in isoform 4 and isoform 5 (PubMed:18521183). {ECO:0000305|PubMed:18521183}.
CautionIt is uncertain whether Met-1 or Met-214 is the initiator in isoform 4 and isoform 5. {ECO:0000305}.
CautionPubMed:2507249 describes a peptide sequence containing a GlcNAc glycosylated Ser in position 164 while it is an Arg residue according to others. {ECO:0000305}.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:10660600};
DiseaseNeuropathy, hereditary sensory and autonomic, 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves. {ECO:0000269|PubMed:15060842, ECO:0000269|PubMed:15911806, ECO:0000269|PubMed:18521183}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseasePseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269|PubMed:11498583}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationBy hypertonicity. Activation requires autophosphorylation of Ser-382. Phosphorylation of Ser-378 also promotes increased activity (By similarity). {ECO:0000250|UniProtKB:Q9JIH7}.
FunctionSerine/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. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15060842}.
InteractionO95747:OXSR1; NbExp=2; IntAct=EBI-457907, EBI-620853; P62136:PPP1CA; NbExp=2; IntAct=EBI-457907, EBI-357253; P29101:Syt2 (xeno); NbExp=2; IntAct=EBI-457907, EBI-458017;
PtmO-glycosylated. {ECO:0000269|PubMed:2507249}.
PtmUbiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a BCR(KLHL2) complex, leading to proteasomal degradation. {ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23838290}.
Sequence CautionSequence=AAF31483.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; Sequence=AAI30468.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=AAI30470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; Sequence=DAA04494.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:10660600}.
SubunitInteracts with SYT2 (By similarity). Interacts with WNK3 and WNK4 (By similarity). Interacts with KLHL3. {ECO:0000250, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23576762}.
Tissue SpecificityWidely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and connecting tubule (CNT) of the nephron. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11571656, ECO:0000269|PubMed:14645531, ECO:0000269|PubMed:22701532}.
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