Search Results

Overview

Uniprot IDQ9BYP7
Protein NameSerine/threonine-protein kinase WNK3
Gene NameWNK3
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
111 VKYEQCSKSTSEISK

Function

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)

Protein Sequence

10 MATDSGDPAS 20 TEDSEKPDGI 30 SFENRVPQVA 40 ATLTVEARLK 50 EKNSTFSASG 60 ETVERKRFFR 70 KSVEMTEDDK 80 VAESSPKDER 90 IKAAMNIPRV 100 DKLPSNVLRG 110 GQEVKYEQCS 120 KSTSEISKDC 130 FKEKNEKEME 140 EEAEMKAVAT 150 SPSGRFLKFD 160 IELGRGAFKT 170 VYKGLDTETW 180 VEVAWCELQD 190 RKLTKAEQQR 200 FKEEAEMLKG 210 LQHPNIVRFY 220 DSWESILKGK 230 KCIVLVTELM 240 TSGTLKTYLK 250 RFKVMKPKVL 260 RSWCRQILKG 270 LQFLHTRTPP 280 IIHRDLKCDN 290 IFITGPTGSV 300 KIGDLGLATL 310 MRTSFAKSVI 320 GTPEFMAPEM 330 YEEHYDESVD 340 VYAFGMCMLE 350 MATSEYPYSE 360 CQNAAQIYRK 370 VTSGIKPASF 380 NKVTDPEVKE 390 IIEGCIRQNK 400 SERLSIRDLL 410 NHAFFAEDTG 420 LRVELAEEDD 430 CSNSSLALRL 440 WVEDPKKLKG 450 KHKDNEAIEF 460 SFNLETDTPE 470 EVAYEMVKSG 480 FFHESDSKAV 490 AKSIRDRVTP 500 IKKTREKKPA 510 GCLEERRDSQ 520 CKSMGNVFPQ 530 PQNTTLPLAP 540 AQQTGAECEE 550 TEVDQHVRQQ 560 LLQRKPQQHC 570 SSVTGDNLSE 580 AGAASVIHSD 590 TSSQPSVAYS 600 SNQTMGSQMV 610 SNIPQAEVNV 620 PGQIYSSQQL 630 VGHYQQVSGL 640 QKHSKLTQPQ 650 ILPLVQGQST 660 VLPVHVLGPT 670 VVSQPQVSPL 680 TVQKVPQIKP 690 VSQPVGAEQQ 700 AALLKPDLVR 710 SLNQDVATTK 720 ENVSSPDNPS 730 GNGKQDRIKQ 740 RRASCPRPEK 750 GTKFQLTVLQ 760 VSTSGDNMVE 770 CQLETHNNKM 780 VTFKFDVDGD 790 APEDIADYMV 800 EDNFVLESEK 810 EKFVEELRAI 820 VGQAQEILHV 830 HFATERATGV 840 DSITVDSNSS 850 QTGSSEQVQI 860 NSTSTQTSNE 870 SAPQSSPVGR 880 WRFCINQTIR 890 NRETQSPPSL 900 QHSMSAVPGR 910 HPLPSPKNTS 920 NKEISRDTLL 930 TIENNPCHRA 940 LFTSKSEHKD 950 VVDGKISECA 960 SVETKQPAIL 970 YQVEDNRQIM 980 APVTNSSSYS 990 TTSVRAVPAE 1000 CEGLTKQASI 1010 FIPVYPCHQT 1020 ASQADALMSH 1030 PGESTQTSGN 1040 SLTTLAFDQK 1050 PQTLSVQQPA 1060 MDAEFISQEG 1070 ETTVNTEASS 1080 PKTVIPTQTP 1090 GLEPTTLQPT 1100 TVLESDGERP 1110 PKLEFADNRI 1120 KTLDEKLRNL 1130 LYQEHSISSI 1140 YPESQKDTQS 1150 IDSPFSSSAE 1160 DTLSCPVTEV 1170 IAISHCGIKD 1180 SPVQSPNFQQ 1190 TGSKLLSNVA 1200 ASQPANISVF 1210 KRDLNVITSV 1220 PSELCLHEMS 1230 SDASLPGDPE 1240 AYPAAVSSGG 1250 AIHLQTGGGY 1260 FGLSFTCPSL 1270 KNPISKKSWT 1280 RKLKSWAYRL 1290 RQSTSFFKRS 1300 KVRQVETEEM 1310 RSAIAPDPIP 1320 LTRESTADTR 1330 ALNRCKAMSG 1340 SFQRGRFQVI 1350 TIPQQQSAKM 1360 TSFGIEHISV 1370 FSETNHSSEE 1380 AFIKTAKSQL 1390 VEIEPATQNP 1400 KTSFSYEKLQ 1410 ALQETCKENK 1420 GVPKQGDNFL 1430 SFSAACETDV 1440 SSVTPEKEFE 1450 ETSATGSSMQ 1460 SGSELLLKER 1470 EILTAGKQPS 1480 SDSEFSASLA 1490 GSGKSVAKTG 1500 PESNQCLPHH 1510 EEQAYAQTQS 1520 SLFYSPSSPM 1530 SSDDESEIED 1540 EDLKVELQRL 1550 REKHIQEVVN 1560 LQTQQNKELQ 1570 ELYERLRSIK 1580 DSKTQSTEIP 1590 LPPASPRRPR 1600 SFKSKLRSRP 1610 QSLTHVDNGI 1620 VATGKSCLIN 1630 ELENPLCVES 1640 NAASCQQSPA 1650 SKKGMFTDDL 1660 HKLVDDWTKE 1670 AVGNSLIKPS 1680 LNQLKQSQHK 1690 LETENWNKVS 1700 ENTPSTMGYT 1710 STWISSLSQI 1720 RGAVPTSLPQ 1730 GLSLPSFPGP 1740 LSSYGMPHVC 1750 QYNAVAGAGY 1760 PVQWVGISGT 1770 TQQSVVIPAQ 1780 SGGPFQPGMN 1790 MQAFPTSSVQ 1800 NPATIPPGPK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005912 adherens junction
Cellular Component GO:0005923 bicellular tight junction
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0140693 molecular condensate scaffold activity
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0044325 transmembrane transporter binding
Molecular Function GO:0141109 transporter activator activity
Biological Process GO:0006884 cell volume homeostasis
Biological Process GO:0071474 cellular hyperosmotic response
Biological Process GO:0006974 DNA damage response
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0035633 maintenance of blood-brain barrier
Biological Process GO:0140694 membraneless organelle assembly
Biological Process GO:0050801 monoatomic ion homeostasis
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:0090188 negative regulation of pancreatic juice secretion
Biological Process GO:1903077 negative regulation of protein localization to plasma membrane
Biological Process GO:0007231 osmosensory signaling pathway
Biological Process GO:0051928 positive regulation of calcium ion transport
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:0010800 positive regulation of peptidyl-threonine phosphorylation
Biological Process GO:1903078 positive regulation of protein localization to plasma membrane
Biological Process GO:2000651 positive regulation of sodium ion transmembrane transporter activity
Biological Process GO:0010765 positive regulation of sodium ion transport
Biological Process GO:0072659 protein localization to plasma membrane
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0090279 regulation of calcium ion import
Biological Process GO:1904062 regulation of monoatomic cation transmembrane transport
Biological Process GO:0070294 renal sodium ion absorption

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.