Protein: Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Q3UH66)
Organism: Mus musculus (Mouse)
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 SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5. Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression. Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1. WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity.
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9Y3S1}. Cell membrane {ECO:0000250|UniProtKB:Q9Y3S1}.
Sequence: MDGDGGRRDAPGALMEAGRGTGSAGMAEPRARAARLGPQRFLRRSVVESDQEEPPGLEAAETPSAQPPQPLQRRVLLLCKTRRLIAERARGRPAAPAPAAPAAPPGSPSVPSDPGPERAGTQEPSPDPTTASAAATQVPDGGPRQEEAPAPTQEDAGTTEAKPEPGRARKDEPEEEEDDEDDLKAVATSLDGRFLKFDIELGRGSFKTVYKGLDTETWVEVAWCELQDRKLTKLERQRFKEEAEMLKGLQHPNIVRFYDFWESSAKGKRCIVLVTELMTSGTLKTYLKRFKVMKPKVLRSWCRQILKGLLFLHTRTPPIIHRDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEHYDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRKVTCGIKPASFEKVHDPEIKEIIGECICKNKEERYEIKDLLSHAFFAEDTGVRVELAEEDHGRKSTIALRLWVEDPKKLKGKPKDNGAIEFTFDLEKETPDEVAQEMIDSGFFHESDVKIVAKSIRDRVALIQWRRERIWPALQSQEPKDSGSPDKARGLPAPLQVQVTYHAQSGQPGQPEPEEPEADQHLLPPTLPASVTSLASDSTFDSGQGSTVYSDSQSSQQSMVLSSLVDTAPTPASCVCSPPVSEGPGLTHSLPTLGAFQQPATVPGLSVGPVPPPARPPLLQQHFPESSMSFTPVLPPPSTPVPTGPSQPAPPVQQPLPMAQPPTLPQVLAPQPMGTVQPVPSHLPPYLAPTSQVVAPAQLKPLQMPQPPLQPLAQVPPQMPQMPVVPPITPLTGLDGLPQTLTDLPAANVAPVPPPQYFSPAVILPSLTTPLPTSPALPMQAVKLPHPPGTPLAVPCQTIVPNAPAAIPLLAVAPQGVAALSIHPAVAQIPAQPVYPAAFPQMVPGDIPPSPHHTVQSLRATPPQLASPVPPQPVQPSVIHLPEQAAPTAASGTQVLLGHPPSYTADVAAPVSAVSLPPAVLSPPLPDTLLPTVPDLLPKVPSSLAPTVVAASQSAPAQTSSLLLPTNPPLPTGPAVAGPCPAVQLMVEVAQEEQVSQDKPPGPPQSSESFGGSDVTSGRDLSDSCEGTFGGGRLEGRTARKHHRRSTRARSRQERASRPRLTILNVCNTGDKMVECQLETHNHKMVTFKFDLDGDAPDEIATYMVEHDFILPAERETFIEQMKDVMDKAEDMLSEDTDADHGSDTGTSPPHLGTCGLATGEENRQSQANAPVYQQNVLHTGKRWFIICPVAEHPATDTSESSPPLPLSSLQPEASQDPAPYPDQLSLTDKPSFPAAQQLLSQAGSSNPPGGASAPLAPSSPPVTTVIPAAPATSTVPESAAGTAMQAGGPGTHQGPASVHETLQPLAETRSAQCTAQPLSTGQGPCTPALEASRCSTGLGEPISTREVSTQGEPLPASVPEPSPPTGATQSVPGQPPPPLPITVGAISLAAPQLPSPPLGPTAPPPPPSALESDGEGPPPRVGFVDNTIKSLDEKLRTLLYQEHVPTSSASAGTPMEASDRDFTLEPLRGDLPSALSDKTPSLTQQTQPSLEKSETAPAGWALAQREQGASSPMTAESSSSNTLGCDSDAGQVASDSSTAPSVPQDASGSSVPTHMDPKDQNSSVPREALAAPMQSGPGSFTVGSPAQLRGARDSGSPHKRPGQQDNSSPAKTVGRFSVVSTQDEWTLASPHSLRYSAPPDVYLDEIPSSPEVKLAVRRVQTASSIEVGVEEPASSDSGDERPRRRSQVQKQSSLPGTGGVASDFVKKATAFLHRSSRAGSLGPETPSRAGVKVPTISITSFHSQSSYISSDNDSEFEDADIKKELRSLREKHLKEISELQSQQKQEIEALYRRLGKPLPPNVGFFHTAPPMGRRRKTSKSKLKAGKLLNPLVQQLKVVASSTGHLSDSSRGPPTKDPRGTKAVQTQQPCSVRASLSTDICSGLASDGGGARGQGWTVYHPTSERGAYKSSSKPRARFLSGPVSVSIWSALKRLCLGKEHSSSLYDSPGSSTSSLAPGPEPGPQPTLHVQAQVNNSNNKKGTFTDDLHKLVDEWTTKTVGAAQVKPTLNQLKQTQKLHDMEASGDARATSVPRAAVGASCLAPAPGPLSTTATPGATPALPVPIPDPESEKPD
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [200-762]
- IPR000719: Protein kinase domain (domain) [195-453]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [319-331]
- IPR024678: Serine/threonine-protein kinase OSR1/WNK, CCT domain (domain) [474-537]
- IPR056865: Serine/threonine-protein kinase WNK, CCTL2 domain (domain) [1135-1208]
- IPR050588: With No Lysine (K) Ser/Thr Protein Kinase (family) [174-1893]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0042592 (homeostatic process), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048870 (cell motility), GO:0051051 (negative regulation of transport), GO:0055085 (transmembrane transport), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0002684 (positive regulation of immune system process), GO:0051234 (establishment of localization), GO:0002682 (regulation of immune system process), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0003008 (system process), GO:0034260 (negative regulation of GTPase activity), GO:0048878 (chemical homeostasis), GO:0065008 (regulation of biological quality), GO:0019725 (cellular homeostasis), GO:0044237 (cellular metabolic process), GO:0050900 (leukocyte migration), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0002253 (activation of immune response), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0050801 (monoatomic ion homeostasis), GO:0002764 (immune response-regulating signaling pathway), GO:0050790 (regulation of catalytic activity), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0098660 (inorganic ion transmembrane transport), GO:0044092 (negative regulation of molecular function), GO:0019538 (protein metabolic process), GO:0044057 (regulation of system process), GO:0071674 (mononuclear cell migration), GO:0034762 (regulation of transmembrane transport), GO:0008217 (regulation of blood pressure), GO:0098771 (inorganic ion homeostasis), GO:0034220 (monoatomic ion transmembrane transport), GO:0043170 (macromolecule metabolic process), GO:0003013 (circulatory system process), GO:0010033 (response to organic substance), GO:0051048 (negative regulation of secretion), GO:0006793 (phosphorus metabolic process), GO:0055082 (intracellular chemical homeostasis), GO:0060457 (negative regulation of digestive system process), GO:0050878 (regulation of body fluid levels), GO:0050776 (regulation of immune response), GO:0002757 (immune response-activating signaling pathway), GO:0070887 (cellular response to chemical stimulus), GO:0006810 (transport), GO:0050778 (positive regulation of immune response), GO:0007166 (cell surface receptor signaling pathway), GO:0016477 (cell migration), GO:0098655 (monoatomic cation transmembrane transport), GO:0034097 (response to cytokine), GO:0043086 (negative regulation of catalytic activity), GO:0055075 (potassium ion homeostasis), GO:0002768 (immune response-regulating cell surface receptor signaling pathway), GO:0008015 (blood circulation), GO:0071310 (cellular response to organic substance), GO:0051336 (regulation of hydrolase activity), GO:0034765 (regulation of monoatomic ion transmembrane transport), GO:0045777 (positive regulation of blood pressure), GO:0006796 (phosphate-containing compound metabolic process), GO:0055081 (monoatomic anion homeostasis), GO:0006873 (intracellular monoatomic ion homeostasis), GO:0006811 (monoatomic ion transport), GO:0036211 (protein modification process), GO:0002429 (immune response-activating cell surface receptor signaling pathway), GO:0043412 (macromolecule modification), GO:0098662 (inorganic cation transmembrane transport), GO:0055080 (monoatomic cation homeostasis), GO:0003073 (regulation of systemic arterial blood pressure), GO:0044058 (regulation of digestive system process), GO:0055064 (chloride ion homeostasis), GO:0051046 (regulation of secretion), GO:0072676 (lymphocyte migration), GO:0043269 (regulation of monoatomic ion transport), GO:0019221 (cytokine-mediated signaling pathway), GO:0006812 (monoatomic cation transport), GO:0051346 (negative regulation of hydrolase activity), GO:0006468 (protein phosphorylation), GO:0035725 (sodium ion transmembrane transport), GO:0010959 (regulation of metal ion transport), GO:0018193 (peptidyl-amino acid modification), GO:0071345 (cellular response to cytokine stimulus), GO:0050851 (antigen receptor-mediated signaling pathway), GO:0016310 (phosphorylation), GO:0043087 (regulation of GTPase activity), GO:1990868 (response to chemokine), GO:0003084 (positive regulation of systemic arterial blood pressure), GO:1904062 (regulation of monoatomic cation transmembrane transport), GO:0070098 (chemokine-mediated signaling pathway), GO:1990869 (cellular response to chemokine), GO:1902305 (regulation of sodium ion transmembrane transport), GO:0050852 (T cell receptor signaling pathway), GO:0030001 (metal ion transport), GO:0002028 (regulation of sodium ion transport), GO:0018210 (peptidyl-threonine modification), GO:0018105 (peptidyl-serine phosphorylation), GO:0018107 (peptidyl-threonine phosphorylation), GO:0018209 (peptidyl-serine modification), GO:0006814 (sodium ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)