WNK3_HUMAN
ID WNK3_HUMAN Reviewed; 1800 AA.
AC Q9BYP7; B1AKG2; Q5JRC1; Q6JP76; Q8TCX6; Q9HCK6;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Serine/threonine-protein kinase WNK3 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:17975670};
DE AltName: Full=Protein kinase lysine-deficient 3 {ECO:0000312|HGNC:HGNC:14543};
DE AltName: Full=Protein kinase with no lysine 3 {ECO:0000303|PubMed:11571656};
GN Name=WNK3 {ECO:0000312|HGNC:HGNC:14543};
GN Synonyms=KIAA1566 {ECO:0000312|EMBL:BAB13392.1},
GN PRKWNK3 {ECO:0000312|HGNC:HGNC:14543};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:CAC32455.2};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND CHROMOSOMAL
RP LOCATION.
RC TISSUE=Brain {ECO:0000269|PubMed:11571656};
RX PubMed=11571656; DOI=10.1038/sj.onc.1204726;
RA Verissimo F., Jordan P.;
RT "WNK kinases, a novel protein kinase subfamily in multi-cellular
RT organisms.";
RL Oncogene 20:5562-5569(2001).
RN [2] {ECO:0000305}
RP SEQUENCE REVISION TO N-TERMINUS.
RA Jordan P.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=15194194; DOI=10.1016/j.gene.2004.03.009;
RA Holden S., Cox J., Raymond F.L.;
RT "Cloning, genomic organization, alternative splicing and expression
RT analysis of the human gene WNK3 (PRKWNK3).";
RL Gene 335:109-119(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-1800 (ISOFORM 3).
RC TISSUE=Brain {ECO:0000269|PubMed:10997877};
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [6]
RP FUNCTION, MUTAGENESIS OF ASP-294, AND TISSUE SPECIFICITY.
RX PubMed=16275913; DOI=10.1073/pnas.0508303102;
RA Rinehart J., Kahle K.T., de Los Heros P., Vazquez N., Meade P.,
RA Wilson F.H., Hebert S.C., Gimenez I., Gamba G., Lifton R.P.;
RT "WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-
RT Cl- cotransporters required for normal blood pressure homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16777-16782(2005).
RN [7]
RP FUNCTION.
RX PubMed=16275911; DOI=10.1073/pnas.0508307102;
RA Kahle K.T., Rinehart J., de Los Heros P., Louvi A., Meade P., Vazquez N.,
RA Hebert S.C., Gamba G., Gimenez I., Lifton R.P.;
RT "WNK3 modulates transport of Cl- in and out of cells: implications for
RT control of cell volume and neuronal excitability.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16783-16788(2005).
RN [8]
RP FUNCTION.
RX PubMed=16357011; DOI=10.1113/jphysiol.2005.102202;
RA Leng Q., Kahle K.T., Rinehart J., MacGregor G.G., Wilson F.H.,
RA Canessa C.M., Lifton R.P., Hebert S.C.;
RT "WNK3, a kinase related to genes mutated in hereditary hypertension with
RT hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1).";
RL J. Physiol. (Lond.) 571:275-286(2006).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16501604; DOI=10.1038/sj.onc.1209449;
RA Verissimo F., Silva E., Morris J.D., Pepperkok R., Jordan P.;
RT "Protein kinase WNK3 increases cell survival in a caspase-3-dependent
RT pathway.";
RL Oncogene 25:4172-4182(2006).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH WNK1 AND WNK4, AND ACTIVITY
RP REGULATION.
RX PubMed=17975670; DOI=10.1172/jci32033;
RA Yang C.L., Zhu X., Ellison D.H.;
RT "The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase
RT signaling complex.";
RL J. Clin. Invest. 117:3403-3411(2007).
RN [11]
RP FUNCTION.
RX PubMed=18768590; DOI=10.1152/ajprenal.90229.2008;
RA Zhang W., Na T., Peng J.B.;
RT "WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via
RT a kinase-dependent pathway.";
RL Am. J. Physiol. 295:F1472-F1484(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
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 [14]
RP FUNCTION.
RX PubMed=20525693; DOI=10.1074/jbc.m110.103432;
RA Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S.,
RA Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.;
RT "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium
RT channel are regulated by multiple with no lysine (WNK) family members.";
RL J. Biol. Chem. 285:25161-25167(2010).
RN [15]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 4), AND MUTAGENESIS OF ASP-294.
RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011;
RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A.,
RA Pasantes-Morales H., Gamba G., Mercado A.;
RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.";
RL Am. J. Physiol. 301:C601-C608(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP UBIQUITINATION BY KLHL2.
RX PubMed=23838290; DOI=10.1016/j.bbrc.2013.06.104;
RA Takahashi D., Mori T., Wakabayashi M., Mori Y., Susa K., Zeniya M.,
RA Sohara E., Rai T., Sasaki S., Uchida S.;
RT "KLHL2 interacts with and ubiquitinates WNK kinases.";
RL Biochem. Biophys. Res. Commun. 437:457-462(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1638, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-704; CYS-854; THR-998; GLU-1169;
RP ILE-1375; PHE-1533 AND PRO-1634.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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 (PubMed:16275913, PubMed:16275911, PubMed:16357011).
CC Phosphorylates WNK4. Regulates the phosphorylation of SLC12A1 and
CC SLC12A2. Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by
CC enhancing their membrane expression level via a kinase-dependent
CC pathway (PubMed:18768590). Inhibits the activity of KCNJ1 by decreasing
CC its expression at the cell membrane in a non-catalytic manner.
CC {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913,
CC ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604,
CC ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590,
CC ECO:0000269|PubMed:20525693}.
CC -!- FUNCTION: Isoform 1, isoform 2, isoform 3 and isoform 4 stimulate the
CC activity of SLC12A1, SLC12A2 and SLC12A3 and inhibit the activity of
CC SLC12A4, SLC12A5, SLC12A6 and SLC12A7. According to PubMed:19470686,
CC isoform 1 inhibits the activity of SLC12A3.
CC {ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:21613606}.
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:0000269|PubMed:17975670};
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:0000269|PubMed:17975670};
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 308. Phosphorylation of Ser-304 also promotes increased activity (By
CC similarity). Kinase activity is inhibited by WNK4.
CC {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:17975670}.
CC -!- SUBUNIT: Interacts with WNK1 and WNK4. {ECO:0000269|PubMed:17975670}.
CC -!- INTERACTION:
CC Q9BYP7; P42574: CASP3; NbExp=2; IntAct=EBI-1182602, EBI-524064;
CC Q9BYP7; P52954: LBX1; NbExp=3; IntAct=EBI-1182602, EBI-20141748;
CC Q9BYP7; Q04864-2: REL; NbExp=3; IntAct=EBI-1182602, EBI-10829018;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16501604}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9BYP7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BYP7-2; Sequence=VSP_041933;
CC Name=3;
CC IsoId=Q9BYP7-3; Sequence=VSP_041932, VSP_041933;
CC Name=4;
CC IsoId=Q9BYP7-4; Sequence=VSP_041932;
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, kidney, liver and
CC pancreas, and in fetal tissues including placenta, fetal brain, lung
CC and kidney. Very low levels of expression were also detected in fetal
CC heart, thymus, liver and spleen. Isoform 1 is brain-specific. Isoform 3
CC is kidney-specific. {ECO:0000269|PubMed:11571656,
CC ECO:0000269|PubMed:15194194, ECO:0000269|PubMed:16275913}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL2) complex, leading to its
CC degradation. {ECO:0000269|PubMed:23838290}.
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; AJ409088; CAC32455.2; -; mRNA.
DR EMBL; AY082340; AAL99253.1; -; mRNA.
DR EMBL; AY352048; AAR89465.1; -; mRNA.
DR EMBL; AL049793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z84469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB046786; BAB13392.1; -; mRNA.
DR CCDS; CCDS14357.1; -. [Q9BYP7-1]
DR CCDS; CCDS35302.1; -. [Q9BYP7-3]
DR RefSeq; NP_001002838.1; NM_001002838.3. [Q9BYP7-3]
DR RefSeq; NP_065973.2; NM_020922.4. [Q9BYP7-1]
DR RefSeq; XP_006724656.1; XM_006724593.3. [Q9BYP7-3]
DR RefSeq; XP_011529104.1; XM_011530802.2. [Q9BYP7-4]
DR RefSeq; XP_016885230.1; XM_017029741.1. [Q9BYP7-1]
DR RefSeq; XP_016885231.1; XM_017029742.1. [Q9BYP7-1]
DR RefSeq; XP_016885232.1; XM_017029743.1. [Q9BYP7-1]
DR RefSeq; XP_016885233.1; XM_017029744.1. [Q9BYP7-1]
DR RefSeq; XP_016885234.1; XM_017029745.1. [Q9BYP7-2]
DR PDB; 5NKP; X-ray; 2.80 A; C/D=537-547.
DR PDB; 5O1V; X-ray; 1.72 A; A/B=132-414.
DR PDB; 5O21; X-ray; 2.06 A; A/B=132-414.
DR PDB; 5O23; X-ray; 2.25 A; A/B=132-414.
DR PDB; 5O26; X-ray; 2.38 A; A/B=133-414.
DR PDB; 5O2B; X-ray; 2.04 A; A/B=132-414.
DR PDB; 5O2C; X-ray; 2.40 A; A=123-500.
DR PDBsum; 5NKP; -.
DR PDBsum; 5O1V; -.
DR PDBsum; 5O21; -.
DR PDBsum; 5O23; -.
DR PDBsum; 5O26; -.
DR PDBsum; 5O2B; -.
DR PDBsum; 5O2C; -.
DR AlphaFoldDB; Q9BYP7; -.
DR SMR; Q9BYP7; -.
DR BioGRID; 122422; 22.
DR ELM; Q9BYP7; -.
DR IntAct; Q9BYP7; 34.
DR STRING; 9606.ENSP00000346667; -.
DR BindingDB; Q9BYP7; -.
DR ChEMBL; CHEMBL6055; -.
DR GuidetoPHARMACOLOGY; 2282; -.
DR GlyGen; Q9BYP7; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q9BYP7; -.
DR PhosphoSitePlus; Q9BYP7; -.
DR BioMuta; WNK3; -.
DR DMDM; 353526307; -.
DR EPD; Q9BYP7; -.
DR jPOST; Q9BYP7; -.
DR MassIVE; Q9BYP7; -.
DR MaxQB; Q9BYP7; -.
DR PaxDb; Q9BYP7; -.
DR PeptideAtlas; Q9BYP7; -.
DR PRIDE; Q9BYP7; -.
DR ProteomicsDB; 79674; -. [Q9BYP7-1]
DR ProteomicsDB; 79675; -. [Q9BYP7-2]
DR ProteomicsDB; 79676; -. [Q9BYP7-3]
DR ProteomicsDB; 79677; -. [Q9BYP7-4]
DR ABCD; Q9BYP7; 1 sequenced antibody.
DR Antibodypedia; 26766; 276 antibodies from 29 providers.
DR DNASU; 65267; -.
DR Ensembl; ENST00000354646.6; ENSP00000346667.2; ENSG00000196632.11. [Q9BYP7-1]
DR Ensembl; ENST00000375159.6; ENSP00000364301.2; ENSG00000196632.11. [Q9BYP7-1]
DR Ensembl; ENST00000375169.7; ENSP00000364312.3; ENSG00000196632.11. [Q9BYP7-3]
DR GeneID; 65267; -.
DR KEGG; hsa:65267; -.
DR UCSC; uc004dtc.3; human. [Q9BYP7-1]
DR CTD; 65267; -.
DR DisGeNET; 65267; -.
DR GeneCards; WNK3; -.
DR HGNC; HGNC:14543; WNK3.
DR HPA; ENSG00000196632; Tissue enhanced (epididymis, testis).
DR MIM; 300358; gene.
DR neXtProt; NX_Q9BYP7; -.
DR OpenTargets; ENSG00000196632; -.
DR PharmGKB; PA33784; -.
DR VEuPathDB; HostDB:ENSG00000196632; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000160145; -.
DR HOGENOM; CLU_000550_1_2_1; -.
DR InParanoid; Q9BYP7; -.
DR OMA; ENNPCQH; -.
DR OrthoDB; 27514at2759; -.
DR PhylomeDB; Q9BYP7; -.
DR TreeFam; TF315363; -.
DR PathwayCommons; Q9BYP7; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q9BYP7; -.
DR SIGNOR; Q9BYP7; -.
DR BioGRID-ORCS; 65267; 12 hits in 726 CRISPR screens.
DR ChiTaRS; WNK3; human.
DR GeneWiki; WNK3; -.
DR GenomeRNAi; 65267; -.
DR Pharos; Q9BYP7; Tchem.
DR PRO; PR:Q9BYP7; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BYP7; protein.
DR Bgee; ENSG00000196632; Expressed in corpus epididymis and 140 other tissues.
DR ExpressionAtlas; Q9BYP7; baseline and differential.
DR Genevisible; Q9BYP7; HS.
DR GO; GO:0005912; C:adherens junction; ISS:BHF-UCL.
DR GO; GO:0005923; C:bicellular tight junction; ISS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006884; P:cell volume homeostasis; IMP:ARUK-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0050801; P:ion homeostasis; IMP:UniProtKB.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; ISS:ARUK-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; IBA:GO_Central.
DR GO; GO:0007231; P:osmosensory signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IMP:UniProtKB.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA: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; IDA:BHF-UCL.
DR GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0090279; P:regulation of calcium ion import; IMP: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 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..1800
FT /note="Serine/threonine-protein kinase WNK3"
FT /id="PRO_0000086823"
FT DOMAIN 147..405
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 707..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 834..868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 880..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1060..1086
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1431..1453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1465..1496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1571..1600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..723
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 724..738
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1437..1453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1466..1492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 294
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 227..230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 277
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:21406692"
FT MOD_RES 304
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 308
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 1070
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80XP9"
FT MOD_RES 1585
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80XP9"
FT MOD_RES 1638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1248..1294
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10997877,
FT ECO:0000303|PubMed:11571656"
FT /id="VSP_041932"
FT VAR_SEQ 1614..1624
FT /note="GKSCLINELEN -> D (in isoform 3 and isoform 2)"
FT /evidence="ECO:0000303|PubMed:10997877,
FT ECO:0000303|PubMed:11571656"
FT /id="VSP_041933"
FT VARIANT 704
FT /note="Q -> H (in dbSNP:rs56077971)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041323"
FT VARIANT 854
FT /note="S -> C (in a lung squamous cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041324"
FT VARIANT 998
FT /note="A -> T (in dbSNP:rs56404148)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041325"
FT VARIANT 1169
FT /note="K -> E (in dbSNP:rs55903619)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041326"
FT VARIANT 1375
FT /note="T -> I (in dbSNP:rs55879434)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041327"
FT VARIANT 1533
FT /note="L -> F (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041328"
FT VARIANT 1634
FT /note="S -> P (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041329"
FT MUTAGEN 294
FT /note="D->A: Catalytically inactive form. Inhibits sodium-
FT coupled chloride cotransporters and activates potassium-
FT coupled chloride cotransporters."
FT /evidence="ECO:0000269|PubMed:16275913,
FT ECO:0000269|PubMed:21613606"
FT CONFLICT 10
FT /note="S -> N (in Ref. 3; AAL99253)"
FT /evidence="ECO:0000305"
FT CONFLICT 431..432
FT /note="WV -> RD (in Ref. 5; BAB13392)"
FT /evidence="ECO:0000305"
FT CONFLICT 1211
FT /note="P -> S (in Ref. 5; BAB13392)"
FT /evidence="ECO:0000305"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:5O2B"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 146..156
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:5O1V"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:5O23"
FT HELIX 185..200
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 222..228
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 235..239
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 247..265
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:5O1V"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 297..301
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 304..310
FT /evidence="ECO:0007829|PDB:5O21"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 328..343
FT /evidence="ECO:0007829|PDB:5O1V"
FT TURN 347..350
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:5O26"
FT HELIX 354..362
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 368..372
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 376..385
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 396..400
FT /evidence="ECO:0007829|PDB:5O1V"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:5O1V"
FT STRAND 408..417
FT /evidence="ECO:0007829|PDB:5O2C"
FT STRAND 424..433
FT /evidence="ECO:0007829|PDB:5O2C"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:5O2C"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:5O2C"
FT STRAND 447..453
FT /evidence="ECO:0007829|PDB:5O2C"
FT TURN 454..456
FT /evidence="ECO:0007829|PDB:5O2C"
FT HELIX 459..468
FT /evidence="ECO:0007829|PDB:5O2C"
FT HELIX 474..476
FT /evidence="ECO:0007829|PDB:5O2C"
FT HELIX 477..494
FT /evidence="ECO:0007829|PDB:5O2C"
FT HELIX 542..545
FT /evidence="ECO:0007829|PDB:5NKP"
SQ SEQUENCE 1800 AA; 198416 MW; 1766D6AC8C7DE864 CRC64;
MATDSGDPAS TEDSEKPDGI SFENRVPQVA ATLTVEARLK EKNSTFSASG ETVERKRFFR
KSVEMTEDDK VAESSPKDER IKAAMNIPRV DKLPSNVLRG GQEVKYEQCS KSTSEISKDC
FKEKNEKEME EEAEMKAVAT SPSGRFLKFD IELGRGAFKT VYKGLDTETW VEVAWCELQD
RKLTKAEQQR FKEEAEMLKG LQHPNIVRFY DSWESILKGK KCIVLVTELM TSGTLKTYLK
RFKVMKPKVL RSWCRQILKG LQFLHTRTPP IIHRDLKCDN IFITGPTGSV KIGDLGLATL
MRTSFAKSVI GTPEFMAPEM YEEHYDESVD VYAFGMCMLE MATSEYPYSE CQNAAQIYRK
VTSGIKPASF NKVTDPEVKE IIEGCIRQNK SERLSIRDLL NHAFFAEDTG LRVELAEEDD
CSNSSLALRL WVEDPKKLKG KHKDNEAIEF SFNLETDTPE EVAYEMVKSG FFHESDSKAV
AKSIRDRVTP IKKTREKKPA GCLEERRDSQ CKSMGNVFPQ PQNTTLPLAP AQQTGAECEE
TEVDQHVRQQ LLQRKPQQHC SSVTGDNLSE AGAASVIHSD TSSQPSVAYS SNQTMGSQMV
SNIPQAEVNV PGQIYSSQQL VGHYQQVSGL QKHSKLTQPQ ILPLVQGQST VLPVHVLGPT
VVSQPQVSPL TVQKVPQIKP VSQPVGAEQQ AALLKPDLVR SLNQDVATTK ENVSSPDNPS
GNGKQDRIKQ RRASCPRPEK GTKFQLTVLQ VSTSGDNMVE CQLETHNNKM VTFKFDVDGD
APEDIADYMV EDNFVLESEK EKFVEELRAI VGQAQEILHV HFATERATGV DSITVDSNSS
QTGSSEQVQI NSTSTQTSNE SAPQSSPVGR WRFCINQTIR NRETQSPPSL QHSMSAVPGR
HPLPSPKNTS NKEISRDTLL TIENNPCHRA LFTSKSEHKD VVDGKISECA SVETKQPAIL
YQVEDNRQIM APVTNSSSYS TTSVRAVPAE CEGLTKQASI FIPVYPCHQT ASQADALMSH
PGESTQTSGN SLTTLAFDQK PQTLSVQQPA MDAEFISQEG ETTVNTEASS PKTVIPTQTP
GLEPTTLQPT TVLESDGERP PKLEFADNRI KTLDEKLRNL LYQEHSISSI YPESQKDTQS
IDSPFSSSAE DTLSCPVTEV IAISHCGIKD SPVQSPNFQQ TGSKLLSNVA ASQPANISVF
KRDLNVITSV PSELCLHEMS SDASLPGDPE AYPAAVSSGG AIHLQTGGGY FGLSFTCPSL
KNPISKKSWT RKLKSWAYRL RQSTSFFKRS KVRQVETEEM RSAIAPDPIP LTRESTADTR
ALNRCKAMSG SFQRGRFQVI TIPQQQSAKM TSFGIEHISV FSETNHSSEE AFIKTAKSQL
VEIEPATQNP KTSFSYEKLQ ALQETCKENK GVPKQGDNFL SFSAACETDV SSVTPEKEFE
ETSATGSSMQ SGSELLLKER EILTAGKQPS SDSEFSASLA GSGKSVAKTG PESNQCLPHH
EEQAYAQTQS SLFYSPSSPM SSDDESEIED EDLKVELQRL REKHIQEVVN LQTQQNKELQ
ELYERLRSIK DSKTQSTEIP LPPASPRRPR SFKSKLRSRP QSLTHVDNGI VATGKSCLIN
ELENPLCVES NAASCQQSPA SKKGMFTDDL HKLVDDWTKE AVGNSLIKPS LNQLKQSQHK
LETENWNKVS ENTPSTMGYT STWISSLSQI RGAVPTSLPQ GLSLPSFPGP LSSYGMPHVC
QYNAVAGAGY PVQWVGISGT TQQSVVIPAQ SGGPFQPGMN MQAFPTSSVQ NPATIPPGPK
