A0A8I5ZNK2
uniprot
A0A8I5ZNK2
canonical
activity_regulation
ACTIVITY REGULATION: Activated following phosphorylation by WNK kinases (WNK1, WNK2, WNK3 or WNK4). {ECO:0000269|PubMed:16083423, ECO:0000269|PubMed:22544747}.
uniprot
proteins
amino_acid_sequence
MSEDSSALPWSINRDDYELQEVIGSGATAVVQAAYCAPKKERVAIKRINLEKCQTSMDELLKEIQAMSQCHHPNIVSYYTSFVVKDELWLVMKLLSGGSVLDIIKHIVAKGEHKGGVLDESTIATILREVLEGLEYLHKNGQIHRDVKAGNILLGEDGSVQIADFGVSAFLATGGDITRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADIWSFGITAIELATGAAPYHKYPPMKVLMLTLQNDPPSLDTGVQDKEMLKKYGKSFRKMISLCLQKDPEKRPTAAELLRHKFFQKAKNKEFLQEKILQRAPTISERSKKVRRVPGSSGRLHKTEDGGWEWSDDEFDEESEEGKAAISQLRSCPTQQHCLCLLQLFSAADPMGTLLQVPEQISAHLPQPASQMPTQPAQVSLLPPAEPAKPAQARSSGERSQETKVPISLVLRLRNSKKELNDIRFEFTPGRDTAEGVSQELISAGLVDGRDLVIVAANLQKIVEEPQSNRSVTFKLASGVEGSDIPDDGKLIGFAQLSIS
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:22544747). Specifically recognizes and binds proteins with a RFXV motif (By similarity). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (By similarity). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (By similarity). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:22544747). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (By similarity). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (By similarity). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (By similarity). Phosphorylates RELL1, RELL2 and RELT (By similarity). Phosphorylates PAK1. Phosphorylates PLSCR1 in the presence of RELT (By similarity). {ECO:0000250|UniProtKB:O95747, ECO:0000269|PubMed:22544747}.
uniprot
proteins
mass_dalton
58360
uniprot
proteins
mutagenesis
MUTAGEN 164; /note="D->A: Abolished serine/threonine-protein kinase activity."; /evidence="ECO:0000269|PubMed:16083423"; MUTAGEN 185; /note="T->A: Decreased serine/threonine-protein kinase activity."; /evidence="ECO:0000269|PubMed:16083423"; MUTAGEN 185; /note="T->E: Mimics phosphorylation; increased serine/threonine-protein kinase activity."; /evidence="ECO:0000269|PubMed:16083423
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-185 by WNK kinases (WNK1, WNK2, WNK3 or WNK4) is required for activation (PubMed:16083423). Autophosphorylated; promoting its activity (By similarity). {ECO:0000250|UniProtKB:O95747, ECO:0000269|PubMed:16083423}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
protein_family
STE20 subfamily
uniprot
proteins
pubmed
15057822
uniprot
proteins
pubmed
16083423
uniprot
proteins
pubmed
22544747
uniprot
proteins
sequence_length
528
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95747}.
uniprot
proteins