Serine/threonine-protein kinase WNK3 (EC 2.7.11.1) (Protein kinase lysine-deficient 3) (Protein kinase with no lysine 3)
1_MATDS 6_ GDPAS 11_ TEDSE 16_ KPDGI 21_ SFENR 26_ VPQVA 31_ ATLTV 36_ EARLK 41_ EKNST 46_ FSASG 51_ ETVER 56_ KRFFR 61_ KSVEM 66_ TEDDK 71_ VAESS 76_ PKDER 81_ IKAAM 86_ NIPRV 91_ DKLPS 96_ NVLRG 101_ GQEVK 106_ YEQCS 111_ KSTSE 116_ ISKDC 121_ FKEKN 126_ EKEME 131_ EEAEM 136_ KAVAT 141_ SPSGR 146_ FLKFD 151_ IELGR 156_ GAFKT 161_ VYKGL 166_ DTETW 171_ VEVAW 176_ CELQD 181_ RKLTK 186_ AEQQR 191_ FKEEA 196_ EMLKG 201_ LQHPN 206_ IVRFY 211_ DSWES 216_ ILKGK 221_ KCIVL 226_ VTELM 231_ TSGTL 236_ KTYLK 241_ RFKVM 246_ KPKVL 251_ RSWCR 256_ QILKG 261_ LQFLH 266_ TRTPP 271_ IIHRD 276_ LKCDN 281_ IFITG 286_ PTGSV 291_ KIGDL 296_ GLATL 301_ MRTSF 306_ AKSVI 311_ GTPEF 316_ MAPEM 321_ YEEHY 326_ DESVD 331_ VYAFG 336_ MCMLE 341_ MATSE 346_ YPYSE 351_ CQNAA 356_ QIYRK 361_ VTSGI 366_ KPASF 371_ NKVTD 376_ PEVKE 381_ IIEGC 386_ IRQNK 391_ SERLS 396_ IRDLL 401_ NHAFF 406_ AEDTG 411_ LRVEL 416_ AEEDD 421_ CSNSS 426_ LALRL 431_ WVEDP 436_ KKLKG 441_ KHKDN 446_ EAIEF 451_ SFNLE 456_ TDTPE 461_ EVAYE 466_ MVKSG 471_ FFHES 476_ DSKAV 481_ AKSIR 486_ DRVTP 491_ IKKTR 496_ EKKPA 501_ GCLEE 506_ RRDSQ 511_ CKSMG 516_ NVFPQ 521_ PQNTT 526_ LPLAP 531_ AQQTG 536_ AECEE 541_ TEVDQ 546_ HVRQQ 551_ LLQRK 556_ PQQHC 561_ SSVTG 566_ DNLSE 571_ AGAAS 576_ VIHSD 581_ TSSQP 586_ SVAYS 591_ SNQTM 596_ GSQMV 601_ SNIPQ 606_ AEVNV 611_ PGQIY 616_ SSQQL 621_ VGHYQ 626_ QVSGL 631_ QKHSK 636_ LTQPQ 641_ ILPLV 646_ QGQST 651_ VLPVH 656_ VLGPT 661_ VVSQP 666_ QVSPL 671_ TVQKV 676_ PQIKP 681_ VSQPV 686_ GAEQQ 691_ AALLK 696_ PDLVR 701_ SLNQD 706_ VATTK 711_ ENVSS 716_ PDNPS 721_ GNGKQ 726_ DRIKQ 731_ RRASC 736_ PRPEK 741_ GTKFQ 746_ LTVLQ 751_ VSTSG 756_ DNMVE 761_ CQLET 766_ HNNKM 771_ VTFKF 776_ DVDGD 781_ APEDI 786_ ADYMV 791_ EDNFV 796_ LESEK 801_ EKFVE 806_ ELRAI 811_ VGQAQ 816_ EILHV 821_ HFATE 826_ RATGV 831_ DSITV 836_ DSNSS 841_ QTGSS 846_ EQVQI 851_ NSTST 856_ QTSNE 861_ SAPQS 866_ SPVGR 871_ WRFCI 876_ NQTIR 881_ NRETQ 886_ SPPSL 891_ QHSMS 896_ AVPGR 901_ HPLPS 906_ PKNTS 911_ NKEIS 916_ RDTLL 921_ TIENN 926_ PCHRA 931_ LFTSK 936_ SEHKD 941_ VVDGK 946_ ISECA 951_ SVETK 956_ QPAIL 961_ YQVED 966_ NRQIM 971_ APVTN 976_ SSSYS 981_ TTSVR 986_ AVPAE 991_ CEGLT 996_ KQASI 1001_ FIPVY 1006_ PCHQT 1011_ ASQAD 1016_ ALMSH 1021_ PGEST 1026_ QTSGN 1031_ SLTTL 1036_ AFDQK 1041_ PQTLS 1046_ VQQPA 1051_ MDAEF 1056_ ISQEG 1061_ ETTVN 1066_ TEASS 1071_ PKTVI 1076_ PTQTP 1081_ GLEPT 1086_ TLQPT 1091_ TVLES 1096_ DGERP 1101_ PKLEF 1106_ ADNRI 1111_ KTLDE 1116_ KLRNL 1121_ LYQEH 1126_ SISSI 1131_ YPESQ 1136_ KDTQS 1141_ IDSPF 1146_ SSSAE 1151_ DTLSC 1156_ PVTEV 1161_ IAISH 1166_ CGIKD 1171_ SPVQS 1176_ PNFQQ 1181_ TGSKL 1186_ LSNVA 1191_ ASQPA 1196_ NISVF 1201_ KRDLN 1206_ VITSV 1211_ PSELC 1216_ LHEMS 1221_ SDASL 1226_ PGDPE 1231_ AYPAA 1236_ VSSGG 1241_ AIHLQ 1246_ TGGGY 1251_ FGLSF 1256_ TCPSL 1261_ KNPIS 1266_ KKSWT 1271_ RKLKS 1276_ WAYRL 1281_ RQSTS 1286_ FFKRS 1291_ KVRQV 1296_ ETEEM 1301_ RSAIA 1306_ PDPIP 1311_ LTRES 1316_ TADTR 1321_ ALNRC 1326_ KAMSG 1331_ SFQRG 1336_ RFQVI 1341_ TIPQQ 1346_ QSAKM 1351_ TSFGI 1356_ EHISV 1361_ FSETN 1366_ HSSEE 1371_ AFIKT 1376_ AKSQL 1381_ VEIEP 1386_ ATQNP 1391_ KTSFS 1396_ YEKLQ 1401_ ALQET 1406_ CKENK 1411_ GVPKQ 1416_ GDNFL 1421_ SFSAA 1426_ CETDV 1431_ SSVTP 1436_ EKEFE 1441_ ETSAT 1446_ GSSMQ 1451_ SGSEL 1456_ LLKER 1461_ EILTA 1466_ GKQPS 1471_ SDSEF 1476_ SASLA 1481_ GSGKS 1486_ VAKTG 1491_ PESNQ 1496_ CLPHH 1501_ EEQAY 1506_ AQTQS 1511_ SLFYS 1516_ PSSPM 1521_ SSDDE 1526_ SEIED 1531_ EDLKV 1536_ ELQRL 1541_ REKHI 1546_ QEVVN 1551_ LQTQQ 1556_ NKELQ 1561_ ELYER 1566_ LRSIK 1571_ DSKTQ 1576_ STEIP 1581_ LPPAS 1586_ PRRPR 1591_ SFKSK 1596_ LRSRP 1601_ QSLTH 1606_ VDNGI 1611_ VATGK 1616_ SCLIN 1621_ ELENP 1626_ LCVES 1631_ NAASC 1636_ QQSPA 1641_ SKKGM 1646_ FTDDL 1651_ HKLVD 1656_ DWTKE 1661_ AVGNS 1666_ LIKPS 1671_ LNQLK 1676_ QSQHK 1681_ LETEN 1686_ WNKVS 1691_ ENTPS 1696_ TMGYT 1701_ STWIS 1706_ SLSQI 1711_ RGAVP 1716_ TSLPQ 1721_ GLSLP 1726_ SFPGP 1731_ LSSYG 1736_ MPHVC 1741_ QYNAV 1746_ AGAGY 1751_ PVQWV 1756_ GISGT 1761_ TQQSV 1766_ VIPAQ 1771_ SGGPF 1776_ QPGMN 1781_ MQAFP 1786_ TSSVQ 1791_NPATI
1: Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 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 WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590)