WNK3_MOUSE
ID WNK3_MOUSE Reviewed; 1757 AA.
AC Q80XP9; H6WJI2; H6WJI3;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 3.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Serine/threonine-protein kinase WNK3 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9BYP7};
DE AltName: Full=Protein kinase lysine-deficient 3 {ECO:0000312|MGI:MGI:2652875};
DE AltName: Full=Protein kinase with no lysine 3 {ECO:0000305};
GN Name=Wnk3 {ECO:0000312|MGI:MGI:2652875};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Shmukler B.E., Alper S.L.;
RT "Mouse Wnk3 gene encodes multiple continuous open reading frames.";
RL Submitted (DEC-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1296-1757.
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND ALTERNATIVE SPLICING.
RX PubMed=19470686; DOI=10.1681/asn.2008050542;
RA Glover M., Zuber A.M., O'Shaughnessy K.M.;
RT "Renal and brain isoforms of WNK3 have opposite effects on NCCT
RT expression.";
RL J. Am. Soc. Nephrol. 20:1314-1322(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-1039; SER-1550 AND
RP SER-1553, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=21317537; DOI=10.1172/jci43475;
RA Yang D., Li Q., So I., Huang C.L., Ando H., Mizutani A., Seki G.,
RA Mikoshiba K., Thomas P.J., Muallem S.;
RT "IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK
RT kinase pathway.";
RL J. Clin. Invest. 121:956-965(2011).
CC -!- FUNCTION: Serine/threonine kinase which plays an important role in the
CC regulation of electrolyte homeostasis, cell signaling, survival and
CC proliferation. Acts as an activator and inhibitor of sodium-coupled
CC chloride cotransporters and potassium-coupled chloride cotransporters
CC respectively. Activates SLC12A1, SLC12A2, SLC12A3, SCNN1A, SCNN1B,
CC SCNN1D and SGK1. Inhibits SLC12A4, SLC12A5, SLC12A6 and SLC12A7.
CC Phosphorylates WNK4. Increases Ca(2+) influx mediated by TRPV5 and
CC TRPV6 by enhancing their membrane expression level via a kinase-
CC dependent pathway. Inhibits KCNJ1 by decreasing its expression at the
CC cell membrane in a non-catalytic manner. {ECO:0000269|PubMed:19470686}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9BYP7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9BYP7};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- ACTIVITY REGULATION: Activation requires autophosphorylation of Ser-
CC 307. Phosphorylation of Ser-303 also promotes increased activity.
CC Kinase activity is inhibited by WNK4 (By similarity).
CC {ECO:0000250|UniProtKB:Q9BYP7, ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: Interacts with WNK1 and WNK4. {ECO:0000250|UniProtKB:Q9BYP7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BYP7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80XP9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80XP9-2; Sequence=VSP_041934;
CC -!- TISSUE SPECIFICITY: Expressed in pancreatic duct (PubMed:21317537).
CC {ECO:0000269|PubMed:21317537}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL2) complex, leading to its
CC degradation. {ECO:0000250|UniProtKB:Q9BYP7}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. WNK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- CAUTION: Was named WNK/'with no lysine(K)' because key residues for
CC catalysis, including the lysine involved in ATP binding, are either not
CC conserved or differ compared to the residues described in other kinase
CC family proteins. {ECO:0000250|UniProtKB:Q9H4A3}.
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DR EMBL; JQ247189; AEZ01402.1; -; mRNA.
DR EMBL; JQ247190; AEZ01403.1; -; mRNA.
DR EMBL; AL732420; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL807396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043119; AAH43119.1; -; mRNA.
DR EMBL; BC060731; AAH60731.1; -; mRNA.
DR CCDS; CCDS72450.1; -. [Q80XP9-2]
DR CCDS; CCDS72451.1; -. [Q80XP9-1]
DR RefSeq; NP_001258607.1; NM_001271678.1. [Q80XP9-1]
DR RefSeq; NP_001258608.1; NM_001271679.1. [Q80XP9-2]
DR RefSeq; XP_006528933.1; XM_006528870.3. [Q80XP9-1]
DR RefSeq; XP_006528934.1; XM_006528871.3. [Q80XP9-1]
DR RefSeq; XP_006528935.1; XM_006528872.3. [Q80XP9-1]
DR RefSeq; XP_006528936.1; XM_006528873.3. [Q80XP9-1]
DR RefSeq; XP_006528937.1; XM_006528874.3.
DR RefSeq; XP_011246131.1; XM_011247829.2. [Q80XP9-1]
DR RefSeq; XP_011246132.1; XM_011247830.2. [Q80XP9-1]
DR AlphaFoldDB; Q80XP9; -.
DR SMR; Q80XP9; -.
DR BioGRID; 235005; 4.
DR IntAct; Q80XP9; 1.
DR STRING; 10090.ENSMUSP00000138839; -.
DR iPTMnet; Q80XP9; -.
DR PhosphoSitePlus; Q80XP9; -.
DR MaxQB; Q80XP9; -.
DR PeptideAtlas; Q80XP9; -.
DR PRIDE; Q80XP9; -.
DR ProteomicsDB; 299792; -. [Q80XP9-1]
DR ProteomicsDB; 299793; -. [Q80XP9-2]
DR Antibodypedia; 26766; 276 antibodies from 29 providers.
DR DNASU; 279561; -.
DR Ensembl; ENSMUST00000184392; ENSMUSP00000139037; ENSMUSG00000041245. [Q80XP9-1]
DR Ensembl; ENSMUST00000184730; ENSMUSP00000138822; ENSMUSG00000041245. [Q80XP9-2]
DR GeneID; 279561; -.
DR KEGG; mmu:279561; -.
DR UCSC; uc009upa.3; mouse. [Q80XP9-2]
DR UCSC; uc029xnn.2; mouse. [Q80XP9-1]
DR CTD; 65267; -.
DR MGI; MGI:2652875; Wnk3.
DR VEuPathDB; HostDB:ENSMUSG00000041245; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000160145; -.
DR HOGENOM; CLU_000550_1_1_1; -.
DR InParanoid; Q80XP9; -.
DR OMA; ENNPCQH; -.
DR OrthoDB; 27514at2759; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 279561; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Wnk3; mouse.
DR PRO; PR:Q80XP9; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q80XP9; protein.
DR Bgee; ENSMUSG00000041245; Expressed in medial preoptic region and 165 other tissues.
DR ExpressionAtlas; Q80XP9; baseline and differential.
DR GO; GO:0005912; C:adherens junction; IDA:BHF-UCL.
DR GO; GO:0005923; C:bicellular tight junction; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019869; F:chloride channel inhibitor activity; ISO:MGI.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0006884; P:cell volume homeostasis; IMP:ARUK-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0050801; P:ion homeostasis; ISO:MGI.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; IMP:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IMP:UniProtKB.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; IBA:GO_Central.
DR GO; GO:0007231; P:osmosensory signaling pathway; ISO:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:1903288; P:positive regulation of potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0090279; P:regulation of calcium ion import; ISS:UniProtKB.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IMP:ARUK-UCL.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1..1757
FT /note="Serine/threonine-protein kinase WNK3"
FT /id="PRO_0000278775"
FT DOMAIN 146..404
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..85
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 674..705
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1404..1440
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1479..1498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1536..1574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1621..1650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1734..1757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..689
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..704
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1404..1421
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1622..1650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 293
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 226..229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 303
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 307
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 1039
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1550
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1553
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1595
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYP7"
FT VAR_SEQ 1217..1263
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_041934"
SQ SEQUENCE 1757 AA; 193991 MW; 3E5B070772BE6725 CRC64;
MATDSGEPAS TEDSEKPDGV SFENRAARAV APLTVEARIK EKYSTFSASG ENIERKRFFR
KSVEMTEDDK VAESSRRDER KAATNISRVD KVPTNVLRGG QEVKYEQCSK ATSESSKDCF
KEKTEKEMEE EAEMKAVATS PSGRFLKFDI ELGRGAFKTV YKGLDTETWV EVAWCELQDR
KLTKAEQQRF KEEAEMLKGL QHPNIVRFYD SWESTLKGKK CIVLVTELMT SGTLKTYLKR
FKVMKPKVLR SWCRQILKGL QFLHTRTPPI IHRDLKCDNI FITGPTGSVK IGDLGLATLM
RTSFAKSVIG TPEFMAPEMY EEHYDESVDV YAFGMCMLEM ATSEYPYSEC QNAAQIYRKV
TSGIKPASFN KVTDPEVKEI IEGCIRQNKS ERLSIKDLLN HAFFAEDTGL RVELAEEDDC
SNSSLALRLW VEDPKKLKGK HKDNEAIEFS FNLEADTPEE VAYEMVKSGF FHESDSKAVA
KSIRDRVTLI KKIREKKPAG CLEERRDSQC KYVRNVLPQQ QTATLQPTPG PHTAAEYEET
EVDQHVRQQF LQGKPQQQSS SVRGDTSSEP TAGPVLHSDT SSHPTVAYSS NQTTSSQEQP
KLTQSPVLPV VQGQSSVMPI YAAGVGVVSQ SQISPLTIQK VSQIKPVSQP IGAEQQATLQ
NPDFVRSLNQ DVTSVKENTN NPDTPSGNGK QDRNKQRRAS CPRPEKGTKF QLTVLQVSVS
GDNMVECQLE THNNKMVTFK FDVDGDAPED IADYMVEDNF VLENEKEKFV EELRAIVGQA
QEILHVHSAV EKSIGVDSVA LESNSNQTGS SEQVLINSAS TQTSNESAPQ SSPVGRWRFC
INQTIKNREA QSPPSLQPSM AMVPGLHPFP SSRNTSNQAI SQNTVFTIEN NPGHRELFTS
KLDHKDVVDG KIGEHASIET EQSSISYQVE DDRQIMTPAT DNSNYSAALV CPVPGECEAL
TSQAGMFMPT YPNQQAAVLA DVHIAYPGES VPIGGNAALT SVLVSSDQKP QSLSVQQPTI
DAEFISKEGE TTVNTETSSP KAVIATQTPG FEPAVILPAT ILESDGERPP KMEFADNRIK
TLDEKLRNLL YQEHSISSIC PESQKDTQSI DSPFSSSAED ILSYSMPEVI AISHCGIQDS
PAQSPNFQQT GSKILSNVAA SQPAHISVFK KDLNVITSVP SELCLHEMSP DASLPGDPEA
YPAAVSSDGT IHLQTGGGYF GLSFTCPSLK NPISRKSWTR KLKSWAYRLR QSTSFFKRSK
VRQVETEDKR SAIASDPIPL TREFSSDTRA LSRCKAMSGS FQRGRFQVIT VPQQQPVKMM
SFGKDHRPPF NKTTVQSSEQ ALTFAEAAVS QLIEVEPAMP THKASVSSRK LRTLYETFKE
DKGDPEQGDI VSYSTACETS VSSVATEKNV TSTTEVSVQS GSEPLDKEKN ESTPGKQTCT
NEFSATLAGN RKSVTKTRPE GDQYLPLREE QAYAQTQNSL FYSPSSPMSS DNESEIEDED
LKVELQRLRE KHIQEVVSLQ TQQNKELQEL YERLRATKDN KAQSSEVPLS PASPRRPRSF
KSKLRSRPQS MTHSDNLVVK DALGVESNTV SCQQSPASKK GMFTDDLHKL VDDWTRETVG
HFPSKPSLNQ LKQSQQKSEA ENWNKSCEST PSTMGYTSNW ISSLSQIRGA APTSLPQGLP
LPSFHGPLAS YGMPHVCQYN AVGAAGYPVQ WVGISGPAQQ SVVLPTQSGG LFQPGMNLQS
FPAPPVQNPA SIPPGPK
