Search Results

Overview

Uniprot IDQ9H4A3
Protein NameSerine/threonine-protein kinase WNK1
Gene NameWNK1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1954 QVTTTANKVGRFSVS

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 (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)

Protein Sequence

10 MSGGAAEKQS 20 STPGSLFLSP 30 PAPAPKNGSS 40 SDSSVGEKLG 50 AAAADAVTGR 60 TEEYRRRRHT 70 MDKDSRGAAA 80 TTTTTEHRFF 90 RRSVICDSNA 100 TALELPGLPL 110 SLPQPSIPAA 120 VPQSAPPEPH 130 REETVTATAT 140 SQVAQQPPAA 150 AAPGEQAVAG 160 PAPSTVPSST 170 SKDRPVSQPS 180 LVGSKEEPPP 190 ARSGSGGGSA 200 KEPQEERSQQ 210 QDDIEELETK 220 AVGMSNDGRF 230 LKFDIEIGRG 240 SFKTVYKGLD 250 TETTVEVAWC 260 ELQDRKLTKS 270 ERQRFKEEAE 280 MLKGLQHPNI 290 VRFYDSWEST 300 VKGKKCIVLV 310 TELMTSGTLK 320 TYLKRFKVMK 330 IKVLRSWCRQ 340 ILKGLQFLHT 350 RTPPIIHRDL 360 KCDNIFITGP 370 TGSVKIGDLG 380 LATLKRASFA 390 KSVIGTPEFM 400 APEMYEEKYD 410 ESVDVYAFGM 420 CMLEMATSEY 430 PYSECQNAAQ 440 IYRRVTSGVK 450 PASFDKVAIP 460 EVKEIIEGCI 470 RQNKDERYSI 480 KDLLNHAFFQ 490 EETGVRVELA 500 EEDDGEKIAI 510 KLWLRIEDIK 520 KLKGKYKDNE 530 AIEFSFDLER 540 DVPEDVAQEM 550 VESGYVCEGD 560 HKTMAKAIKD 570 RVSLIKRKRE 580 QRQLVREEQE 590 KKKQEESSLK 600 QQVEQSSASQ 610 TGIKQLPSAS 620 TGIPTASTTS 630 ASVSTQVEPE 640 EPEADQHQQL 650 QYQQPSISVL 660 SDGTVDSGQG 670 SSVFTESRVS 680 SQQTVSYGSQ 690 HEQAHSTGTV 700 PGHIPSTVQA 710 QSQPHGVYPP 720 SSVAQGQSQG 730 QPSSSSLTGV 740 SSSQPIQHPQ 750 QQQGIQQTAP 760 PQQTVQYSLS 770 QTSTSSEATT 780 AQPVSQPQAP 790 QVLPQVSAGK 800 QLPVSQPVPT 810 IQGEPQIPVA 820 TQPSVVPVHS 830 GAHFLPVGQP 840 LPTPLLPQYP 850 VSQIPISTPH 860 VSTAQTGFSS 870 LPITMAAGIT 880 QPLLTLASSA 890 TTAAIPGVST 900 VVPSQLPTLL 910 QPVTQLPSQV 920 HPQLLQPAVQ 930 SMGIPANLGQ 940 AAEVPLSSGD 950 VLYQGFPPRL 960 PPQYPGDSNI 970 APSSNVASVC 980 IHSTVLSPPM 990 PTEVLATPGY 1000 FPTVVQPYVE 1010 SNLLVPMGGV 1020 GGQVQVSQPG 1030 GSLAQAPTTS 1040 SQQAVLESTQ 1050 GVSQVAPAEP 1060 VAVAQTQATQ 1070 PTTLASSVDS 1080 AHSDVASGMS 1090 DGNENVPSSS 1100 GRHEGRTTKR 1110 HYRKSVRSRS 1120 RHEKTSRPKL 1130 RILNVSNKGD 1140 RVVECQLETH 1150 NRKMVTFKFD 1160 LDGDNPEEIA 1170 TIMVNNDFIL 1180 AIERESFVDQ 1190 VREIIEKADE 1200 MLSEDVSVEP 1210 EGDQGLESLQ 1220 GKDDYGFSGS 1230 QKLEGEFKQP 1240 IPASSMPQQI 1250 GIPTSSLTQV 1260 VHSAGRRFIV 1270 SPVPESRLRE 1280 SKVFPSEITD 1290 TVAASTAQSP 1300 GMNLSHSASS 1310 LSLQQAFSEL 1320 RRAQMTEGPN 1330 TAPPNFSHTG 1340 PTFPVVPPFL 1350 SSIAGVPTTA 1360 AATAPVPATS 1370 SPPNDISTSV 1380 IQSEVTVPTE 1390 EGIAGVATST 1400 GVVTSGGLPI 1410 PPVSESPVLS 1420 SVVSSITIPA 1430 VVSISTTSPS 1440 LQVPTSTSEI 1450 VVSSTALYPS 1460 VTVSATSASA 1470 GGSTATPGPK 1480 PPAVVSQQAA 1490 GSTTVGATLT 1500 SVSTTTSFPS 1510 TASQLCIQLS 1520 SSTSTPTLAE 1530 TVVVSAHSLD 1540 KTSHSSTTGL 1550 AFSLSAPSSS 1560 SSPGAGVSSY 1570 ISQPGGLHPL 1580 VIPSVIASTP 1590 ILPQAAGPTS 1600 TPLLPQVPSI 1610 PPLVQPVANV 1620 PAVQQTLIHS 1630 QPQPALLPNQ 1640 PHTHCPEVDS 1650 DTQPKAPGID 1660 DIKTLEEKLR 1670 SLFSEHSSSG 1680 AQHASVSLET 1690 SLVIESTVTP 1700 GIPTTAVAPS 1710 KLLTSTTSTC 1720 LPPTNLPLGT 1730 VALPVTPVVT 1740 PGQVSTPVST 1750 TTSGVKPGTA 1760 PSKPPLTKAP 1770 VLPVGTELPA 1780 GTLPSEQLPP 1790 FPGPSLTQSQ 1800 QPLEDLDAQL 1810 RRTLSPEMIT 1820 VTSAVGPVSM 1830 AAPTAITEAG 1840 TQPQKGVSQV 1850 KEGPVLATSS 1860 GAGVFKMGRF 1870 QVSVAADGAQ 1880 KEGKNKSEDA 1890 KSVHFESSTS 1900 ESSVLSSSSP 1910 ESTLVKPEPN 1920 GITIPGISSD 1930 VPESAHKTTA 1940 SEAKSDTGQP 1950 TKVGRFQVTT 1960 TANKVGRFSV 1970 SKTEDKITDT 1980 KKEGPVASPP 1990 FMDLEQAVLP 2000 AVIPKKEKPE 2010 LSEPSHLNGP 2020 SSDPEAAFLS 2030 RDVDDGSGSP 2040 HSPHQLSSKS 2050 LPSQNLSQSL 2060 SNSFNSSYMS 2070 SDNESDIEDE 2080 DLKLELRRLR 2090 DKHLKEIQDL 2100 QSRQKHEIES 2110 LYTKLGKVPP 2120 AVIIPPAAPL 2130 SGRRRRPTKS 2140 KGSKSSRSSS 2150 LGNKSPQLSG 2160 NLSGQSAASV 2170 LHPQQTLHPP 2180 GNIPESGQNQ 2190 LLQPLKPSPS 2200 SDNLYSAFTS 2210 DGAISVPSLS 2220 APGQGTSSTN 2230 TVGATVNSQA 2240 AQAQPPAMTS 2250 SRKGTFTDDL 2260 HKLVDNWARD 2270 AMNLSGRRGS 2280 KGHMNYEGPG 2290 MARKFSAPGQ 2300 LCISMTSNLG 2310 GSAPISAASA 2320 TSLGHFTKSM 2330 CPPQQYGFPA 2340 TPFGAQWSGT 2350 GGPAPQPLGQ 2360 FQPVGTASLQ 2370 NFNISNLQKS 2380 ISNPPGSNLR TT

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0043232 intracellular membraneless organelle
Cellular Component GO:0016020 membrane
Cellular Component GO:0072686 mitotic spindle
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0140693 molecular condensate scaffold activity
Molecular Function GO:0019902 phosphatase binding
Molecular Function GO:0030295 protein kinase activator activity
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Biological Process GO:0006884 cell volume homeostasis
Biological Process GO:0071474 cellular hyperosmotic response
Biological Process GO:1990869 cellular response to chemokine
Biological Process GO:0038116 chemokine (C-C motif) ligand 21 signaling pathway
Biological Process GO:0006974 DNA damage response
Biological Process GO:0007507 heart development
Biological Process GO:0030644 intracellular chloride ion homeostasis
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0097022 lymphocyte migration into lymph node
Biological Process GO:0140694 membraneless organelle assembly
Biological Process GO:0055080 monoatomic cation homeostasis
Biological Process GO:0006811 monoatomic ion transport
Biological Process GO:0010507 negative regulation of autophagy
Biological Process GO:0033633 negative regulation of cell-cell adhesion mediated by integrin
Biological Process GO:0034115 negative regulation of heterotypic cell-cell adhesion
Biological Process GO:1903038 negative regulation of leukocyte cell-cell adhesion
Biological Process GO:1903077 negative regulation of protein localization to plasma membrane
Biological Process GO:0031397 negative regulation of protein ubiquitination
Biological Process GO:0051058 negative regulation of small GTPase mediated signal transduction
Biological Process GO:0010766 negative regulation of sodium ion transport
Biological Process GO:0048666 neuron development
Biological Process GO:0045766 positive regulation of angiogenesis
Biological Process GO:0090263 positive regulation of canonical Wnt signaling pathway
Biological Process GO:1903490 positive regulation of mitotic cytokinesis
Biological Process GO:0010820 positive regulation of T cell chemotaxis
Biological Process GO:1904595 positive regulation of termination of RNA polymerase II transcription
Biological Process GO:0055075 potassium ion homeostasis
Biological Process GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0008217 regulation of blood pressure
Biological Process GO:1904062 regulation of monoatomic cation transmembrane transport
Biological Process GO:0010793 regulation of mRNA export from nucleus
Biological Process GO:1902305 regulation of sodium ion transmembrane transport
Biological Process GO:0002028 regulation of sodium ion transport
Biological Process GO:0007165 signal transduction
Biological Process GO:0035725 sodium ion transmembrane transport
Biological Process GO:0050852 T cell receptor signaling pathway

Reference

[1] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.