Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1)
1_MSGGA 6_ AEKQS 11_ STPGS 16_ LFLSP 21_ PAPAP 26_ KNGSS 31_ SDSSV 36_ GEKLG 41_ AAAAD 46_ AVTGR 51_ TEEYR 56_ RRRHT 61_ MDKDS 66_ RGAAA 71_ TTTTT 76_ EHRFF 81_ RRSVI 86_ CDSNA 91_ TALEL 96_ PGLPL 101_ SLPQP 106_ SIPAA 111_ VPQSA 116_ PPEPH 121_ REETV 126_ TATAT 131_ SQVAQ 136_ QPPAA 141_ AAPGE 146_ QAVAG 151_ PAPST 156_ VPSST 161_ SKDRP 166_ VSQPS 171_ LVGSK 176_ EEPPP 181_ ARSGS 186_ GGGSA 191_ KEPQE 196_ ERSQQ 201_ QDDIE 206_ ELETK 211_ AVGMS 216_ NDGRF 221_ LKFDI 226_ EIGRG 231_ SFKTV 236_ YKGLD 241_ TETTV 246_ EVAWC 251_ ELQDR 256_ KLTKS 261_ ERQRF 266_ KEEAE 271_ MLKGL 276_ QHPNI 281_ VRFYD 286_ SWEST 291_ VKGKK 296_ CIVLV 301_ TELMT 306_ SGTLK 311_ TYLKR 316_ FKVMK 321_ IKVLR 326_ SWCRQ 331_ ILKGL 336_ QFLHT 341_ RTPPI 346_ IHRDL 351_ KCDNI 356_ FITGP 361_ TGSVK 366_ IGDLG 371_ LATLK 376_ RASFA 381_ KSVIG 386_ TPEFM 391_ APEMY 396_ EEKYD 401_ ESVDV 406_ YAFGM 411_ CMLEM 416_ ATSEY 421_ PYSEC 426_ QNAAQ 431_ IYRRV 436_ TSGVK 441_ PASFD 446_ KVAIP 451_ EVKEI 456_ IEGCI 461_ RQNKD 466_ ERYSI 471_ KDLLN 476_ HAFFQ 481_ EETGV 486_ RVELA 491_ EEDDG 496_ EKIAI 501_ KLWLR 506_ IEDIK 511_ KLKGK 516_ YKDNE 521_ AIEFS 526_ FDLER 531_ DVPED 536_ VAQEM 541_ VESGY 546_ VCEGD 551_ HKTMA 556_ KAIKD 561_ RVSLI 566_ KRKRE 571_ QRQLV 576_ REEQE 581_ KKKQE 586_ ESSLK 591_ QQVEQ 596_ SSASQ 601_ TGIKQ 606_ LPSAS 611_ TGIPT 616_ ASTTS 621_ ASVST 626_ QVEPE 631_ EPEAD 636_ QHQQL 641_ QYQQP 646_ SISVL 651_ SDGTV 656_ DSGQG 661_ SSVFT 666_ ESRVS 671_ SQQTV 676_ SYGSQ 681_ HEQAH 686_ STGTV 691_ PGHIP 696_ STVQA 701_ QSQPH 706_ GVYPP 711_ SSVAQ 716_ GQSQG 721_ QPSSS 726_ SLTGV 731_ SSSQP 736_ IQHPQ 741_ QQQGI 746_ QQTAP 751_ PQQTV 756_ QYSLS 761_ QTSTS 766_ SEATT 771_ AQPVS 776_ QPQAP 781_ QVLPQ 786_ VSAGK 791_ QLPVS 796_ QPVPT 801_ IQGEP 806_ QIPVA 811_ TQPSV 816_ VPVHS 821_ GAHFL 826_ PVGQP 831_ LPTPL 836_ LPQYP 841_ VSQIP 846_ ISTPH 851_ VSTAQ 856_ TGFSS 861_ LPITM 866_ AAGIT 871_ QPLLT 876_ LASSA 881_ TTAAI 886_ PGVST 891_ VVPSQ 896_ LPTLL 901_ QPVTQ 906_ LPSQV 911_ HPQLL 916_ QPAVQ 921_ SMGIP 926_ ANLGQ 931_ AAEVP 936_ LSSGD 941_ VLYQG 946_ FPPRL 951_ PPQYP 956_ GDSNI 961_ APSSN 966_ VASVC 971_ IHSTV 976_ LSPPM 981_ PTEVL 986_ ATPGY 991_ FPTVV 996_ QPYVE 1001_ SNLLV 1006_ PMGGV 1011_ GGQVQ 1016_ VSQPG 1021_ GSLAQ 1026_ APTTS 1031_ SQQAV 1036_ LESTQ 1041_ GVSQV 1046_ APAEP 1051_ VAVAQ 1056_ TQATQ 1061_ PTTLA 1066_ SSVDS 1071_ AHSDV 1076_ ASGMS 1081_ DGNEN 1086_ VPSSS 1091_ GRHEG 1096_ RTTKR 1101_ HYRKS 1106_ VRSRS 1111_ RHEKT 1116_ SRPKL 1121_ RILNV 1126_ SNKGD 1131_ RVVEC 1136_ QLETH 1141_ NRKMV 1146_ TFKFD 1151_ LDGDN 1156_ PEEIA 1161_ TIMVN 1166_ NDFIL 1171_ AIERE 1176_ SFVDQ 1181_ VREII 1186_ EKADE 1191_ MLSED 1196_ VSVEP 1201_ EGDQG 1206_ LESLQ 1211_ GKDDY 1216_ GFSGS 1221_ QKLEG 1226_ EFKQP 1231_ IPASS 1236_ MPQQI 1241_ GIPTS 1246_ SLTQV 1251_ VHSAG 1256_ RRFIV 1261_ SPVPE 1266_ SRLRE 1271_ SKVFP 1276_ SEITD 1281_ TVAAS 1286_ TAQSP 1291_ GMNLS 1296_ HSASS 1301_ LSLQQ 1306_ AFSEL 1311_ RRAQM 1316_ TEGPN 1321_ TAPPN 1326_ FSHTG 1331_ PTFPV 1336_ VPPFL 1341_ SSIAG 1346_ VPTTA 1351_ AATAP 1356_ VPATS 1361_ SPPND 1366_ ISTSV 1371_ IQSEV 1376_ TVPTE 1381_ EGIAG 1386_ VATST 1391_ GVVTS 1396_ GGLPI 1401_ PPVSE 1406_ SPVLS 1411_ SVVSS 1416_ ITIPA 1421_ VVSIS 1426_ TTSPS 1431_ LQVPT 1436_ STSEI 1441_ VVSST 1446_ ALYPS 1451_ VTVSA 1456_ TSASA 1461_ GGSTA 1466_ TPGPK 1471_ PPAVV 1476_ SQQAA 1481_ GSTTV 1486_ GATLT 1491_ SVSTT 1496_ TSFPS 1501_ TASQL 1506_ CIQLS 1511_ SSTST 1516_ PTLAE 1521_ TVVVS 1526_ AHSLD 1531_ KTSHS 1536_ STTGL 1541_ AFSLS 1546_ APSSS 1551_ SSPGA 1556_ GVSSY 1561_ ISQPG 1566_ GLHPL 1571_ VIPSV 1576_ IASTP 1581_ ILPQA 1586_ AGPTS 1591_ TPLLP 1596_ QVPSI 1601_ PPLVQ 1606_ PVANV 1611_ PAVQQ 1616_ TLIHS 1621_ QPQPA 1626_ LLPNQ 1631_ PHTHC 1636_ PEVDS 1641_ DTQPK 1646_ APGID 1651_ DIKTL 1656_ EEKLR 1661_ SLFSE 1666_ HSSSG 1671_ AQHAS 1676_ VSLET 1681_ SLVIE 1686_ STVTP 1691_ GIPTT 1696_ AVAPS 1701_ KLLTS 1706_ TTSTC 1711_ LPPTN 1716_ LPLGT 1721_ VALPV 1726_ TPVVT 1731_ PGQVS 1736_ TPVST 1741_ TTSGV 1746_ KPGTA 1751_ PSKPP 1756_ LTKAP 1761_ VLPVG 1766_ TELPA 1771_ GTLPS 1776_ EQLPP 1781_ FPGPS 1786_ LTQSQ 1791_ QPLED 1796_ LDAQL 1801_ RRTLS 1806_ PEMIT 1811_ VTSAV 1816_ GPVSM 1821_ AAPTA 1826_ ITEAG 1831_ TQPQK 1836_ GVSQV 1841_ KEGPV 1846_ LATSS 1851_ GAGVF 1856_ KMGRF 1861_ QVSVA 1866_ ADGAQ 1871_ KEGKN 1876_ KSEDA 1881_ KSVHF 1886_ ESSTS 1891_ ESSVL 1896_ SSSSP 1901_ ESTLV 1906_ KPEPN 1911_ GITIP 1916_ GISSD 1921_ VPESA 1926_ HKTTA 1931_ SEAKS 1936_ DTGQP 1941_ TKVGR 1946_ FQVTT 1951_ TANKV 1956_ GRFSV 1961_ SKTED 1966_ KITDT 1971_ KKEGP 1976_ VASPP 1981_ FMDLE 1986_ QAVLP 1991_ AVIPK 1996_ KEKPE 2001_ LSEPS 2006_ HLNGP 2011_ SSDPE 2016_ AAFLS 2021_ RDVDD 2026_ GSGSP 2031_ HSPHQ 2036_ LSSKS 2041_ LPSQN 2046_ LSQSL 2051_ SNSFN 2056_ SSYMS 2061_ SDNES 2066_ DIEDE 2071_ DLKLE 2076_ LRRLR 2081_ DKHLK 2086_ EIQDL 2091_ QSRQK 2096_ HEIES 2101_ LYTKL 2106_ GKVPP 2111_ AVIIP 2116_ PAAPL 2121_ SGRRR 2126_ RPTKS 2131_ KGSKS 2136_ SRSSS 2141_ LGNKS 2146_ PQLSG 2151_ NLSGQ 2156_ SAASV 2161_ LHPQQ 2166_ TLHPP 2171_ GNIPE 2176_ SGQNQ 2181_ LLQPL 2186_ KPSPS 2191_ SDNLY 2196_ SAFTS 2201_ DGAIS 2206_ VPSLS 2211_ APGQG 2216_ TSSTN 2221_ TVGAT 2226_ VNSQA 2231_ AQAQP 2236_ PAMTS 2241_ SRKGT 2246_ FTDDL 2251_ HKLVD 2256_ NWARD 2261_ AMNLS 2266_ GRRGS 2271_ KGHMN 2276_ YEGPG 2281_ MARKF 2286_ SAPGQ 2291_ LCISM 2296_ TSNLG 2301_ GSAPI 2306_ SAASA 2311_ TSLGH 2316_ FTKSM 2321_ CPPQQ 2326_ YGFPA 2331_ TPFGA 2336_ QWSGT 2341_ GGPAP 2346_ QPLGQ 2351_ FQPVG 2356_ TASLQ 2361_ NFNIS 2366_ NLQKS 2371_ ISNPP 2376_GSNLR
1: 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 (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). 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 (PubMed:36318922). 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 (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). 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:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). 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 (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). 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 (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts 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 (PubMed:36373794). 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 (PubMed:33964204)
2: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity)