The following text describes a protein:
Function:
Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx. WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation. The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK. Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity. 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. Also acts as a regulator of angiogenesis in endothelial cells (By similarity). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L. Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding. Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (By similarity). Acts as a negative regulator of autophagy (By similarity). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (By similarity). WNK1 may also play a role in actin cytoskeletal reorganization (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR. Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner. Probably activates SGK1 by acting as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (By similarity). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (By similarity); [Isoform 5]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1. Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport. Down-regulates 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; [Isoform 4]: Kinase-defective isoform produced by alternative promoter usage and alternative splicing.
Miscellaneous:
MISCELLANEOUS: [Isoform 2]: This isoform which includes the HSN2 exon has been identified in human and mouse. The sequence shown here is the result of gene prediction; MISCELLANEOUS: [Isoform 3]: This isoform which includes the HSN2 exon has been identified in human and mouse. The sequence shown here is the result of gene prediction.
Subcellular Localization:
Cytoplasm. Nucleus. Cytoplasm, cytoskeleton, spindle. Note=Mediates formation and localizes to cytoplasmic membraneless compartment in response to hyperosmotic stress. Also localizes to the nucleus (By similarity). Localizes to the mitotic spindle during mitosis (By similarity).
Domain:
The RFXV motifs mediate recognition with downstream kinases OXSR1/OSR1 and STK39/SPAK; Disordered regions undergo liquid-liquid phase separation (LLPS) for the formation of a cytoplasmic membraneless compartment that concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK.
Sequence:
MSDGTAEKQSGTPGFLSPPAPVPKNGSSSDSSVGEKLGAAVADSGIGRTEEYRRRRHTMDKDSRGAAATTTPTEHRFFRRSVICDSNATALELPGLPLSIPQPSVPAVVPQSAPPEPHREETLTATVASQVSQQPSAAASPGEQAVVGSATATVPSSTSKDRPVSQPSLVGSKEEPPPSRSGSGSGGASAKEPQEERNQQQDDIEELETKAVGMSNDGRFLKFDIEIGRGSFKTVYKGLDTETTVEVAWCELQDRKLTKSERQRFKEEAEMLKGLQHPNIVRFYDSWESTVKGKKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTPPIIHRDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDESVDVYAFGMCMLEMATSEYPYSECQNAAQIYRRVTSGVKPASFDKVAIPEVKEIIEGCIRQNKDERYSIKDLLNHAFFQEETGVRVELAEEDDGEKIAIKLWLRIEDIKKLKGKYKDNEAIEFSFDLERDVPEDVAQEMVESGYVCEGDHKTMAKAIKDRVSLIKRKREQRQLVREEQEKRKQEESSFKQQNEQQASVSQAGIQPLSVASTGIPTAPTTSASVSTQVEPEEPEADQHQQLQYQQPSISVLSDGTVDSGQGSSVFTESRVSSQQTVSYGSQHEQAHSIGTAPGHTVSSIQAQSQPHGVYPPSSMAQGQNQGQPSSSLAGVLSSQPVQHPQQQGIQPTVPPQQAVQYSLPQAASSSEGTVQPVSQPQVSAGTQSSTQGVSQAAPPEQTPITQSQPTQPVPLVSSVDSAHSDVASGMSDGNENAPSSSGRHEGRTTKRHYRKSVRSRSRHEKTSRPKLRILNVSNKGDRVVECQLETHNRKMVTFKFDLDGDNPEEIATIMVNNDFILAIERESFVAQVREIIEKADEMLSEDVSVEPEGDQGLESLQGKDDYGFPGSQKLEGEFKQPIAVSSMPQQIGVPTSSLTQVVHSAGRRFIVSPVPESRLRESKIFTSEIPDPVAASTSQGPGMNLSHSASSLSLQQAFSELKHGQMTEGPNTAPPNFNHPGPTFSPFLTSIAGVQTVAASTPSVSVPITSSPLNDISTSVMQSEGALPTDKGIGGVTTSTGVVASGGLTTLSVSETPTLSSAVSSSTAPAVVTVSTTSQPVQASTSGSIASSTGSFPSGTFSTTTGTTVSSVAVPNAKPPTVLLQQVAGNTAGVAIVTSVSTTTPFPAMASQPSLPLGSSTSAPTLAETVVVSAHSLDKASHSSTAGLGLSFCAPSSSSSSGTAVSSSVSQPGIVHPLVISSAIASTPVLPQPAVPTSTPLLPQVPNIPPLVQPVANVPAVQQTLIHSQPQPALLPNQPHTHCPEMDADTQSKAPGIDDIKTLEEKLRSLFSEHSSSGTQHASVSLETPLVVETVTPGIPTTAVAPSKLMTSTTSTCLPPTNLPLGTAGMPVMPVGTPGQVSTPGTHASAPASTATGAKPGTTPPKPSLTKTVVPPVGTELSAGTVPCEQLPPFPGPSLIQTQQPLEDLDAQLRRTLSPETIPVTPAVGPLSTMSSTAVTEAGSQPQKDGTEVHVTASSSGAGVVKMGRFQVSVTMDDAQKERKNRSEDTKSVHFESSTSESSVLSSSSPESTLVKPEPNGITVSGISLDVPDSTHRTPTPEAKSETGQPTKVGRFQVTTTANKVGRFSVSRTEDKVTELKKEGPVTSPFRDSEQTVIPAAIPKKEKPELAEPSHLNGPSSDLEAAFLSRGGEDGSGSPHSPPHLCSKSLPIQTLSQSLSNSFNSSYMSSDNESDIEDEDLRLELRRLREKHLKEIQDLQSRQKHEIESLYTKLGKVPPAVIIPPAAPLSGRRRRPTKSKGSKSSRSSSLGNKSPQLSGNLSGQSGTSVLNPQQTLHPPGNTPETGHNQLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSSTNTVGGTVSSQAAQAQPPAMTSSRKGTFTDDLHKLVDNWARDAMNLSGRRGSKGHMNYEGPGMARKFSAPGQLCISMTSNMGGSTPISAASATSLGHFTKSMCPPQQYGFPAAPFGTQWSGTGGPAPQPLGQFQPVGTTSLQNFNISNLQKSISNPPGSNLRTT