ID   WNK2_HUMAN              Reviewed;        2297 AA.
AC   Q9Y3S1; Q5VWF1; Q5VWF2; Q8IY36; Q9C0A3; Q9H3P4;
DT   02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT   02-FEB-2004, sequence version 4.
DT   27-MAR-2024, entry version 196.
DE   RecName: Full=Serine/threonine-protein kinase WNK2 {ECO:0000305};
DE            EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9H4A3};
DE   AltName: Full=Antigen NY-CO-43;
DE   AltName: Full=Protein kinase lysine-deficient 2 {ECO:0000312|HGNC:HGNC:14542};
DE   AltName: Full=Protein kinase with no lysine 2 {ECO:0000303|PubMed:11571656};
DE   AltName: Full=Serologically defined colon cancer antigen 43;
GN   Name=WNK2 {ECO:0000303|PubMed:11571656, ECO:0000312|HGNC:HGNC:14542};
GN   Synonyms=KIAA1760 {ECO:0000312|EMBL:BAB21851.2}, PRKWNK2
GN   {ECO:0000312|HGNC:HGNC:14542}, SDCCAG43 {ECO:0000312|HGNC:HGNC:14542};
GN   ORFNames=P/OKcl.13;
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;
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND CHROMOSOMAL
RP   LOCATION.
RC   TISSUE=Colon epithelium {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.
RA   Jordan P.;
RL   Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [4] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-845 (ISOFORM 3).
RC   TISSUE=Pancreatic cancer {ECO:0000269|PubMed:11280764};
RX   PubMed=11280764;
RA   Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K.;
RT   "Molecular basis of T cell-mediated recognition of pancreatic cancer
RT   cells.";
RL   Cancer Res. 61:2038-2046(2001).
RN   [5] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-2297 (ISOFORM 2).
RC   TISSUE=Brain {ECO:0000312|EMBL:BAB21851.2};
RX   PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA   Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XIX. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 7:347-355(2000).
RN   [6] {ECO:0000305}
RP   SEQUENCE REVISION.
RA   Ohara O., Nagase T., Kikuno R.;
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [7] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1609-2297 (ISOFORM 4).
RC   TISSUE=Lung {ECO:0000269|PubMed:15489334};
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   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP   AUTOPHOSPHORYLATION.
RX   PubMed=17667937; DOI=10.1038/sj.onc.1210706;
RA   Moniz S., Verissimo F., Matos P., Brazao R., Silva E., Kotelevets L.,
RA   Kotevelets L., Chastre E., Gespach C., Jordan P.;
RT   "Protein kinase WNK2 inhibits cell proliferation by negatively modulating
RT   the activation of MEK1/ERK1/2.";
RL   Oncogene 26:6071-6081(2007).
RN   [9]
RP   ERRATUM OF PUBMED:17667937.
RA   Moniz S., Verissimo F., Matos P., Brazao R., Silva E., Kotelevets L.,
RA   Kotevelets L., Chastre E., Gespach C., Jordan P.;
RL   Oncogene 27:155-155(2008).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX   PubMed=18593598; DOI=10.1016/j.cellsig.2008.06.002;
RA   Moniz S., Matos P., Jordan P.;
RT   "WNK2 modulates MEK1 activity through the Rho GTPase pathway.";
RL   Cell. Signal. 20:1762-1768(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1817 AND SER-1818, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1817 AND SER-1818, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [14]
RP   FUNCTION, TISSUE SPECIFICITY, AND PHOSPHORYLATION AT SER-45; SER-560;
RP   SER-1150; SER-1262; SER-1588; SER-1685; SER-1736; SER-1817; SER-1818;
RP   SER-1862 AND SER-2067.
RX   PubMed=21733846; DOI=10.1074/jbc.m111.222893;
RA   Rinehart J., Vazquez N., Kahle K.T., Hodson C.A., Ring A.M., Gulcicek E.E.,
RA   Louvi A., Bobadilla N.A., Gamba G., Lifton R.P.;
RT   "WNK2 is a novel regulator of essential neuronal cation-chloride
RT   cotransporters.";
RL   J. Biol. Chem. 286:30171-30180(2011).
CC   -!- FUNCTION: Serine/threonine-protein kinase component of the WNK2-
CC       SPAK/OSR1 kinase cascade, which plays an important role in the
CC       regulation of electrolyte homeostasis, cell signaling, survival, and
CC       proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The
CC       WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates
CC       phosphorylation and activation of downstream kinases OXSR1/OSR1 and
CC       STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and
CC       STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating
CC       their activity (By similarity). Acts as an activator and inhibitor of
CC       sodium-coupled chloride cotransporters and potassium-coupled chloride
CC       cotransporters respectively (PubMed:21733846). Activates SLC12A2,
CC       SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846).
CC       Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway
CC       and the downstream cell cycle progression (PubMed:17667937,
CC       PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the
CC       activity of MAP2K1 and this modulation depends on phosphorylation of
CC       MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by
CC       interfering with the activity of PAK1 by controlling the balance of the
CC       activity of upstream regulators of PAK1 activity, RHOA and RAC1, which
CC       display reciprocal activity (PubMed:17667937, PubMed:18593598).
CC       {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937,
CC       ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}.
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:Q9H4A3};
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:Q9H4A3};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC   -!- ACTIVITY REGULATION: Activation requires autophosphorylation of Ser-356
CC       and, to a lower extent, Ser-352 (By similarity).
CC       {ECO:0000250|UniProtKB:Q9JIH7}.
CC   -!- SUBUNIT: Forms a complex with the phosphorylated form of STK39.
CC       {ECO:0000250|UniProtKB:Q3UH66}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17667937,
CC       ECO:0000269|PubMed:18593598}. Cell membrane
CC       {ECO:0000269|PubMed:18593598}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1 {ECO:0000269|PubMed:11571656};
CC         IsoId=Q9Y3S1-1; Sequence=Displayed;
CC       Name=2 {ECO:0000303|PubMed:11214970};
CC         IsoId=Q9Y3S1-2; Sequence=VSP_050643, VSP_050644, VSP_050647;
CC       Name=3 {ECO:0000269|PubMed:11280764};
CC         IsoId=Q9Y3S1-3; Sequence=VSP_050639, VSP_050640, VSP_050641,
CC                                  VSP_050642;
CC       Name=4 {ECO:0000303|PubMed:15489334};
CC         IsoId=Q9Y3S1-4; Sequence=VSP_050645, VSP_050646;
CC   -!- TISSUE SPECIFICITY: Expressed in various cancer cell lines (at protein
CC       level). Predominantly expressed in heart, brain, skeletal muscle and
CC       colon. {ECO:0000269|PubMed:11571656, ECO:0000269|PubMed:17667937,
CC       ECO:0000269|PubMed:21733846}.
CC   -!- PTM: Autophosphorylated (PubMed:18593598, PubMed:21733846).
CC       Autophosphorylation at Ser-352 and Ser-356 promotes its activity (By
CC       similarity). {ECO:0000250|UniProtKB:Q9JIH7,
CC       ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}.
CC   -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence.
CC       {ECO:0000269|PubMed:11280764}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH37965.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/41867/WNK2";
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DR   EMBL; AJ242724; CAB44308.5; -; mRNA.
DR   EMBL; AL354991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL390760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL583839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AB044546; BAB18648.1; -; mRNA.
DR   EMBL; AB051547; BAB21851.2; -; mRNA.
DR   EMBL; BC037965; AAH37965.1; ALT_INIT; mRNA.
DR   CCDS; CCDS75858.1; -. [Q9Y3S1-1]
DR   RefSeq; NP_001269323.1; NM_001282394.1. [Q9Y3S1-1]
DR   RefSeq; XP_005252197.1; XM_005252140.2. [Q9Y3S1-2]
DR   PDB; 6ELM; X-ray; 1.14 A; A=454-549.
DR   PDB; 6FBK; X-ray; 1.74 A; A=454-549.
DR   PDBsum; 6ELM; -.
DR   PDBsum; 6FBK; -.
DR   AlphaFoldDB; Q9Y3S1; -.
DR   SMR; Q9Y3S1; -.
DR   BioGRID; 122423; 37.
DR   ELM; Q9Y3S1; -.
DR   IntAct; Q9Y3S1; 17.
DR   STRING; 9606.ENSP00000297954; -.
DR   BindingDB; Q9Y3S1; -.
DR   ChEMBL; CHEMBL5639; -.
DR   GuidetoPHARMACOLOGY; 2281; -.
DR   GlyCosmos; Q9Y3S1; 2 sites, 1 glycan.
DR   GlyGen; Q9Y3S1; 4 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; Q9Y3S1; -.
DR   PhosphoSitePlus; Q9Y3S1; -.
DR   BioMuta; WNK2; -.
DR   DMDM; 41688799; -.
DR   EPD; Q9Y3S1; -.
DR   jPOST; Q9Y3S1; -.
DR   MassIVE; Q9Y3S1; -.
DR   MaxQB; Q9Y3S1; -.
DR   PaxDb; 9606-ENSP00000297954; -.
DR   PeptideAtlas; Q9Y3S1; -.
DR   ProteomicsDB; 86071; -. [Q9Y3S1-1]
DR   ProteomicsDB; 86072; -. [Q9Y3S1-2]
DR   ProteomicsDB; 86073; -. [Q9Y3S1-3]
DR   ProteomicsDB; 86074; -. [Q9Y3S1-4]
DR   Pumba; Q9Y3S1; -.
DR   Antibodypedia; 28371; 185 antibodies from 26 providers.
DR   DNASU; 65268; -.
DR   Ensembl; ENST00000297954.9; ENSP00000297954.4; ENSG00000165238.17. [Q9Y3S1-1]
DR   Ensembl; ENST00000432730.6; ENSP00000415038.2; ENSG00000165238.17. [Q9Y3S1-2]
DR   GeneID; 65268; -.
DR   KEGG; hsa:65268; -.
DR   UCSC; uc004ati.3; human. [Q9Y3S1-1]
DR   AGR; HGNC:14542; -.
DR   CTD; 65268; -.
DR   DisGeNET; 65268; -.
DR   GeneCards; WNK2; -.
DR   HGNC; HGNC:14542; WNK2.
DR   HPA; ENSG00000165238; Tissue enhanced (heart muscle, skeletal muscle).
DR   MIM; 606249; gene.
DR   neXtProt; NX_Q9Y3S1; -.
DR   OpenTargets; ENSG00000165238; -.
DR   PharmGKB; PA33783; -.
DR   VEuPathDB; HostDB:ENSG00000165238; -.
DR   eggNOG; KOG0584; Eukaryota.
DR   GeneTree; ENSGT00940000157161; -.
DR   InParanoid; Q9Y3S1; -.
DR   OMA; RWFIVCP; -.
DR   OrthoDB; 5478852at2759; -.
DR   PhylomeDB; Q9Y3S1; -.
DR   TreeFam; TF315363; -.
DR   PathwayCommons; Q9Y3S1; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; Q9Y3S1; -.
DR   SIGNOR; Q9Y3S1; -.
DR   BioGRID-ORCS; 65268; 9 hits in 353 CRISPR screens.
DR   ChiTaRS; WNK2; human.
DR   GeneWiki; WNK2; -.
DR   GenomeRNAi; 65268; -.
DR   Pharos; Q9Y3S1; Tchem.
DR   PRO; PR:Q9Y3S1; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q9Y3S1; Protein.
DR   Bgee; ENSG00000165238; Expressed in apex of heart and 161 other cell types or tissues.
DR   ExpressionAtlas; Q9Y3S1; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR   GO; GO:0050801; P:monoatomic ion homeostasis; IMP:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR   GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR   GO; GO:2000651; P:positive regulation of sodium ion transmembrane transporter activity; IMP:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR   CDD; cd14032; STKc_WNK2_like; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR13902; SERINE/THREONINE-PROTEIN KINASE WNK WITH NO LYSINE -RELATED; 1.
DR   PANTHER; PTHR13902:SF10; SERINE_THREONINE-PROTEIN KINASE WNK2; 1.
DR   Pfam; PF12202; OSR1_C; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; Q9Y3S1; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW   Kinase; Membrane; Methylation; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..2297
FT                   /note="Serine/threonine-protein kinase WNK2"
FT                   /id="PRO_0000086822"
FT   DOMAIN          195..453
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..75
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          89..183
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          579..630
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          699..751
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          917..1022
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1117..1185
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1262..1297
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1323..1345
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1374..1480
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1492..1586
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1621..1865
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1970..1990
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2011..2031
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2123..2142
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          2269..2297
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        146..172
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        601..630
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        705..751
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        939..1009
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1117..1148
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1165..1179
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1275..1297
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1324..1339
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1374..1410
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1411..1427
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1443..1472
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1508..1533
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1554..1571
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1672..1687
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1770..1798
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        2273..2291
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        342
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT   BINDING         205
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT   BINDING         275..278
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT   BINDING         325
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT   MOD_RES         19
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3UH66"
FT   MOD_RES         30
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3UH66"
FT   MOD_RES         45
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         352
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT   MOD_RES         356
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT   MOD_RES         560
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1150
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1262
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1588
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1685
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1736
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1817
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT   MOD_RES         1818
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT   MOD_RES         1862
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   MOD_RES         1889
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q3UH66"
FT   MOD_RES         2067
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:21733846"
FT   VAR_SEQ         1..14
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11280764"
FT                   /id="VSP_050639"
FT   VAR_SEQ         680..731
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11280764"
FT                   /id="VSP_050640"
FT   VAR_SEQ         843..845
FT                   /note="LAA -> RTR (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11280764"
FT                   /id="VSP_050641"
FT   VAR_SEQ         846..2297
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:11280764"
FT                   /id="VSP_050642"
FT   VAR_SEQ         1345..1381
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11214970"
FT                   /id="VSP_050643"
FT   VAR_SEQ         2247..2261
FT                   /note="DGALGTARRNQVWFG -> GSCGPRAVSTPTSYT (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11214970"
FT                   /id="VSP_050644"
FT   VAR_SEQ         2248..2254
FT                   /note="GALGTAR -> PESEKPD (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_050645"
FT   VAR_SEQ         2255..2297
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_050646"
FT   VAR_SEQ         2262..2297
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11214970"
FT                   /id="VSP_050647"
FT   VARIANT         828
FT                   /note="V -> M (in dbSNP:rs10761203)"
FT                   /id="VAR_057114"
FT   VARIANT         974
FT                   /note="R -> L (in dbSNP:rs10114908)"
FT                   /id="VAR_059773"
FT   STRAND          458..465
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   STRAND          469..481
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   HELIX           483..485
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   STRAND          496..501
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   TURN            502..504
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   HELIX           507..516
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   HELIX           522..524
FT                   /evidence="ECO:0007829|PDB:6ELM"
FT   HELIX           525..545
FT                   /evidence="ECO:0007829|PDB:6ELM"
SQ   SEQUENCE   2297 AA;  242676 MW;  33D2EF2BFA6A1BD2 CRC64;
     MDGDGGRRDV PGTLMEPGRG AGPAGMAEPR AKAARPGPQR FLRRSVVESD QEEPPGLEAA
     EAPGPQPPQP LQRRVLLLCK TRRLIAERAR GRPAAPAPAA LVAQPGAPGA PADAGPEPVG
     TQEPGPDPIA AAVETAPAPD GGPREEAAAT VRKEDEGAAE AKPEPGRTRR DEPEEEEDDE
     DDLKAVATSL DGRFLKFDIE LGRGSFKTVY KGLDTETWVE VAWCELQDRK LTKLERQRFK
     EEAEMLKGLQ HPNIVRFYDF WESSAKGKRC IVLVTELMTS GTLKTYLKRF KVMKPKVLRS
     WCRQILKGLL FLHTRTPPII HRDLKCDNIF ITGPTGSVKI GDLGLATLKR ASFAKSVIGT
     PEFMAPEMYE EHYDESVDVY AFGMCMLEMA TSEYPYSECQ NAAQIYRKVT CGIKPASFEK
     VHDPEIKEII GECICKNKEE RYEIKDLLSH AFFAEDTGVR VELAEEDHGR KSTIALRLWV
     EDPKKLKGKP KDNGAIEFTF DLEKETPDEV AQEMIESGFF HESDVKIVAK SIRDRVALIQ
     WRRERIWPAL QPKEQQDVGS PDKARGPPVP LQVQVTYHAQ AGQPGPPEPE EPEADQHLLP
     PTLPTSATSL ASDSTFDSGQ GSTVYSDSQS SQQSVMLGSL ADAAPSPAQC VCSPPVSEGP
     VLPQSLPSLG AYQQPTAAPG LPVGSVPAPA CPPSLQQHFP DPAMSFAPVL PPPSTPMPTG
     PGQPAPPGQQ PPPLAQPTPL PQVLAPQPVV PLQPVPPHLP PYLAPASQVG APAQLKPLQM
     PQAPLQPLAQ VPPQMPPIPV VPPITPLAGI DGLPPALPDL PTATVPPVPP PQYFSPAVIL
     PSLAAPLPPA SPALPLQAVK LPHPPGAPLA MPCRTIVPNA PATIPLLAVA PPGVAALSIH
     SAVAQLPGQP VYPAAFPQMA PTDVPPSPHH TVQNMRATPP QPALPPQPTL PPQPVLPPQP
     TLPPQPVLPP QPTRPPQPVL PPQPMLPPQP VLPPQPALPV RPEPLQPHLP EQAAPAATPG
     SQILLGHPAP YAVDVAAQVP TVPVPPAAVL SPPLPEVLLP AAPELLPQFP SSLATVSASV
     QSVPTQTATL LPPANPPLPG GPGIASPCPT VQLTVEPVQE EQASQDKPPG LPQSCESYGG
     SDVTSGKELS DSCEGAFGGG RLEGRAARKH HRRSTRARSR QERASRPRLT ILNVCNTGDK
     MVECQLETHN HKMVTFKFDL DGDAPDEIAT YMVEHDFILQ AERETFIEQM KDVMDKAEDM
     LSEDTDADRG SDPGTSPPHL STCGLGTGEE SRQSQANAPV YQQNVLHTGK RWFIICPVAE
     HPAPEAPESS PPLPLSSLPP EASQGPCRGL TLPCLPWRRA ACGAVFLSLF SAESAQSKQP
     PDSAPYKDQL SSKEQPSFLA SQQLLSQAGP SNPPGAPPAP LAPSSPPVTA LPQDGAAPAT
     STMPEPASGT ASQAGGPGTP QGLTSELETS QPLAETHEAP LAVQPLVVGL APCTPAPEAA
     STRDASAPRE PLPPPAPEPS PHSGTPQPAL GQPAPLLPAA VGAVSLATSQ LPSPPLGPTV
     PPQPPSALES DGEGPPPRVG FVDSTIKSLD EKLRTLLYQE HVPTSSASAG TPVEVGDRDF
     TLEPLRGDQP RSEVCGGDLA LPPVPKEAVS GRVQLPQPLV EKSELAPTRG AVMEQGTSSS
     MTAESSPRSM LGYDRDGRQV ASDSHVVPSV PQDVPAFVRP ARVEPTDRDG GEAGESSAEP
     PPSDMGTVGG QASHPQTLGA RALGSPRKRP EQQDVSSPAK TVGRFSVVST QDEWTLASPH
     SLRYSAPPDV YLDEAPSSPD VKLAVRRAQT ASSIEVGVGE PVSSDSGDEG PRARPPVQKQ
     ASLPVSGSVA GDFVKKATAF LQRPSRAGSL GPETPSRVGM KVPTISVTSF HSQSSYISSD
     NDSELEDADI KKELQSLREK HLKEISELQS QQKQEIEALY RRLGKPLPPN VGFFHTAPPT
     GRRRKTSKSK LKAGKLLNPL VRQLKVVASS TGHLADSSRG PPAKDPAQAS VGLTADSTGL
     SGKAVQTQQP CSVRASLSSD ICSGLASDGG GARGQGWTVY HPTSERVTYK SSSKPRARFL
     SGPVSVSIWS ALKRLCLGKE HSSRSSTSSL APGPEPGPQP ALHVQAQVNN SNNKKGTFTD
     DLHKLVDEWT SKTVGAAQLK PTLNQLKQTQ KLQDMEAQAG WAAPGEARAM TAPRAGVGMP
     RLPPAPGPLS TTVIPGAAPT LSVPTPDGAL GTARRNQVWF GLRVPPTACC GHSTQPRGGQ
     RVGSKTASFA ASDPVRS
//