WNK2_HUMAN
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 03-AUG-2022, entry version 187.
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:0000312|HGNC:HGNC:14542};
GN Synonyms=KIAA1760 {ECO:0000312|EMBL:BAB21851.2},
GN PRKWNK2 {ECO:0000312|HGNC:HGNC:14542},
GN SDCCAG43 {ECO:0000312|HGNC:HGNC:14542}; 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 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 SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and
CC inhibits SLC12A5. Negatively regulates the EGF-induced activation of
CC the ERK/MAPK-pathway and the downstream cell cycle progression. Affects
CC MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this
CC modulation depends on phosphorylation of MAP2K1 by PAK1. 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. {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-
CC 356. Phosphorylation of Ser-352 also promotes increased activity (By
CC similarity). {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. {ECO:0000269|PubMed:18593598,
CC 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="http://atlasgeneticsoncology.org/Genes/WNK2ID41867ch9q22.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 27.
DR ELM; Q9Y3S1; -.
DR IntAct; Q9Y3S1; 19.
DR STRING; 9606.ENSP00000297954; -.
DR BindingDB; Q9Y3S1; -.
DR ChEMBL; CHEMBL5639; -.
DR GuidetoPHARMACOLOGY; 2281; -.
DR GlyGen; Q9Y3S1; 2 sites, 1 O-linked glycan (2 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; Q9Y3S1; -.
DR PeptideAtlas; Q9Y3S1; -.
DR PRIDE; Q9Y3S1; -.
DR ProteomicsDB; 86071; -. [Q9Y3S1-1]
DR ProteomicsDB; 86072; -. [Q9Y3S1-2]
DR ProteomicsDB; 86073; -. [Q9Y3S1-3]
DR ProteomicsDB; 86074; -. [Q9Y3S1-4]
DR Antibodypedia; 28371; 173 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 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; VADIPCC; -.
DR OrthoDB; 27514at2759; -.
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 291 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 159 other tissues.
DR ExpressionAtlas; Q9Y3S1; baseline and differential.
DR Genevisible; Q9Y3S1; HS.
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:0019869; F:chloride channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
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: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:0010766; P:negative regulation of sodium ion transport; IBA:GO_Central.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:1903288; P:positive regulation of potassium ion import across plasma membrane; IBA:GO_Central.
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 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; 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
