WNK1_HUMAN
ID WNK1_HUMAN Reviewed; 2382 AA.
AC Q9H4A3; A1L4B0; C5HTZ5; C5HTZ6; C5HTZ7; H6WZW3; O15052; P54963; Q4VBX9;
AC Q6IFS5; Q86WL5; Q8N673; Q96CZ6; Q9P1S9;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Serine/threonine-protein kinase WNK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:10660600};
DE AltName: Full=Erythrocyte 65 kDa protein;
DE Short=p65;
DE AltName: Full=Kinase deficient protein;
DE AltName: Full=Protein kinase lysine-deficient 1 {ECO:0000312|HGNC:HGNC:14540};
DE AltName: Full=Protein kinase with no lysine 1 {ECO:0000303|PubMed:11571656};
DE Short=hWNK1;
GN Name=WNK1 {ECO:0000312|HGNC:HGNC:14540};
GN Synonyms=HSN2 {ECO:0000303|PubMed:15060842}, KDP,
GN KIAA0344 {ECO:0000312|EMBL:BAA20802.2},
GN PRKWNK1 {ECO:0000312|HGNC:HGNC:14540};
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:CAC15059.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHROMOSOMAL
RP LOCATION, AND VARIANTS PRO-1056; SER-1506 AND ILE-1808.
RC TISSUE=Heart {ECO:0000312|EMBL:CAC15059.1};
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Neuron;
RX PubMed=22701532; DOI=10.1371/journal.pone.0037751;
RA Vidal-Petiot E., Cheval L., Faugeroux J., Malard T., Doucet A.,
RA Jeunemaitre X., Hadchouel J.;
RT "A new methodology for quantification of alternatively spliced exons
RT reveals a highly tissue-specific expression pattern of WNK1 isoforms.";
RL PLoS ONE 7:E37751-E37751(2012).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-1056; SER-1506 AND
RP ILE-1808.
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-668 (ISOFORMS 1/2), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Mammary carcinoma;
RX PubMed=10660600; DOI=10.1074/jbc.275.6.4311;
RA Moore T.M., Garg R., Johnson C., Coptcoat M.J., Ridley A.J., Morris J.D.H.;
RT "PSK, a novel STE20-like kinase derived from prostatic carcinoma that
RT activates the JNK MAPK pathway and regulates actin cytoskeletal
RT organisation.";
RL J. Biol. Chem. 275:4311-4322(2000).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-2382 (ISOFORM 2), AND VARIANTS
RP PRO-1056 AND SER-1506.
RC TISSUE=Brain {ECO:0000312|EMBL:BAA20802.2};
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [7] {ECO:0000305}
RP SEQUENCE REVISION TO N-TERMINUS.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [8]
RP PROTEIN SEQUENCE OF 163-175, AND GLYCOSYLATION.
RX PubMed=2507249; DOI=10.1002/9780470513828.ch7;
RA Hart G.W., Haltiwanger R.S., Holt G.D., Kelly W.G.;
RT "Nucleoplasmic and cytoplasmic glycoproteins.";
RL Ciba Found. Symp. 145:102-118(1989).
RN [9] {ECO:0000305}
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (N-TERMINUS OF ISOFORM 3), ALTERNATIVE
RP PROMOTER USAGE, ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney {ECO:0000269|PubMed:14645531};
RX PubMed=14645531; DOI=10.1128/mcb.23.24.9208-9221.2003;
RA Delaloy C., Lu J., Houot A.-M., Disse-Nicodeme S., Gasc J.-M., Corvol P.,
RA Jeunemaitre X.;
RT "Multiple promoters in the WNK1 gene: one controls expression of a kidney-
RT specific kinase-defective isoform.";
RL Mol. Cell. Biol. 23:9208-9221(2003).
RN [10] {ECO:0000305}
RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1/4/5).
RC TISSUE=Placenta {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 [11]
RP IDENTIFICATION (ISOFORMS 4/5), FUNCTION, AND INVOLVEMENT IN HSAN2A.
RX PubMed=15060842; DOI=10.1086/420795;
RA Lafreniere R.G., MacDonald M.L.E., Dube M.-P., MacFarlane J.,
RA O'Driscoll M., Brais B., Meilleur S., Brinkman R.R., Dadivas O., Pape T.,
RA Platon C., Radomski C., Risler J., Thompson J., Guerra-Escobio A.-M.,
RA Davar G., Breakefield X.O., Pimstone S.N., Green R., Pryse-Phillips W.,
RA Goldberg Y.P., Younghusband H.B., Hayden M.R., Sherrington R.,
RA Rouleau G.A., Samuels M.E.;
RT "Identification of a novel gene (HSN2) causing hereditary sensory and
RT autonomic neuropathy type II through the study of Canadian genetic
RT isolates.";
RL Am. J. Hum. Genet. 74:1064-1073(2004).
RN [12] {ECO:0000305}
RP INVOLVEMENT IN PHA2C.
RX PubMed=11498583; DOI=10.1126/science.1062844;
RA Wilson F.H., Disse-Nicodeme S., Choate K.A., Ishikawa K.,
RA Nelson-Williams C., Desitter I., Gunel M., Milford D.V., Lipkin G.W.,
RA Achard J.-M., Feely M.P., Dussol B., Berland Y., Unwin R.J., Mayan H.,
RA Simon D.B., Farfel Z., Jeunemaitre X., Lifton R.P.;
RT "Human hypertension caused by mutations in WNK kinases.";
RL Science 293:1107-1112(2001).
RN [13]
RP INVOLVEMENT IN HSAN2A.
RX PubMed=15911806; DOI=10.1212/01.wnl.0000161849.29944.43;
RA Roddier K., Thomas T., Marleau G., Gagnon A.M., Dicaire M.J., St Denis A.,
RA Gosselin I., Sarrazin A.M., Larbrisseau A., Lambert M., Vanasse M.,
RA Gaudet D., Rouleau G.A., Brais B.;
RT "Two mutations in the HSN2 gene explain the high prevalence of HSAN2 in
RT French Canadians.";
RL Neurology 64:1762-1767(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2002 AND SER-2032, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1261, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [16]
RP ALTERNATIVE SPLICING (ISOFORMS 4 AND 5), AND INVOLVEMENT IN HSAN2A.
RX PubMed=18521183; DOI=10.1172/jci34088;
RA Shekarabi M., Girard N., Riviere J.B., Dion P., Houle M., Toulouse A.,
RA Lafreniere R.G., Vercauteren F., Hince P., Laganiere J., Rochefort D.,
RA Faivre L., Samuels M., Rouleau G.A.;
RT "Mutations in the nervous system--specific HSN2 exon of WNK1 cause
RT hereditary sensory neuropathy type II.";
RL J. Clin. Invest. 118:2496-2505(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-1261; SER-2011;
RP SER-2012; SER-2027; SER-2029 AND SER-2032, AND IDENTIFICATION BY MASS
RP 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 [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1978, AND IDENTIFICATION BY
RP 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-1261; SER-1978;
RP SER-2032 AND SER-2121, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2027; SER-2029 AND SER-2032,
RP AND IDENTIFICATION BY 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 [24]
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 [25]
RP INTERACTION WITH KLHL3.
RX PubMed=23387299; DOI=10.1042/bj20121903;
RA Ohta A., Schumacher F.R., Mehellou Y., Johnson C., Knebel A.,
RA Macartney T.J., Wood N.T., Alessi D.R., Kurz T.;
RT "The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome
RT interacts with and ubiquitylates WNK isoforms: disease-causing mutations in
RT KLHL3 and WNK4 disrupt interaction.";
RL Biochem. J. 451:111-122(2013).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-167; SER-174;
RP SER-1261; SER-2029; SER-2032; SER-2370 AND SER-2372, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP UBIQUITINATION, AND INTERACTION WITH KLHL3.
RX PubMed=23576762; DOI=10.1073/pnas.1304592110;
RA Shibata S., Zhang J., Puthumana J., Stone K.L., Lifton R.P.;
RT "Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via
RT ubiquitination and degradation of WNK4.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:7838-7843(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167; SER-174; SER-1978 AND
RP SER-2027, AND IDENTIFICATION BY 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 [29] {ECO:0007744|PDB:4PWN}
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 210-482.
RX PubMed=24803536; DOI=10.1126/scisignal.2005050;
RA Piala A.T., Moon T.M., Akella R., He H., Cobb M.H., Goldsmith E.J.;
RT "Chloride sensing by WNK1 involves inhibition of autophosphorylation.";
RL Sci. Signal. 7:RA41-RA41(2014).
RN [30] {ECO:0007744|PDB:5TF9}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 206-483 IN COMPLEX WITH ATP AND
RP ALLOSTERIC INHIBITOR.
RX PubMed=27712055; DOI=10.1021/acschembio.6b00511;
RA Yamada K., Zhang J.H., Xie X., Reinhardt J., Xie A.Q., LaSala D., Kohls D.,
RA Yowe D., Burdick D., Yoshisue H., Wakai H., Schmidt I., Gunawan J.,
RA Yasoshima K., Yue Q.K., Kato M., Mogi M., Idamakanti N., Kreder N.,
RA Drueckes P., Pandey P., Kawanami T., Huang W., Yagi Y.I., Deng Z.,
RA Park H.M.;
RT "Discovery and characterization of allosteric WNK kinase inhibitors.";
RL ACS Chem. Biol. 11:3338-3346(2016).
RN [31]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-1199 AND GLU-1799.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [32]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-141; VAL-149; GLN-419; THR-509;
RP GLY-527; ILE-665; ALA-674; ARG-823; VAL-1546; GLU-1799; ILE-1808; LEU-1823;
RP HIS-1957; CYS-2190; LEU-2362 AND TRP-2380.
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. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls
CC sodium and chloride ion transport by inhibiting the activity of WNK4,
CC by either phosphorylating the kinase or via an interaction between WNK4
CC and the autoinhibitory domain of WNK1. WNK4 regulates the activity of
CC the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by
CC phosphorylation. WNK1 may also play a role in actin cytoskeletal
CC reorganization. Phosphorylates NEDD4L. Acts as a scaffold to inhibit
CC SLC4A4, SLC26A6 as well as CFTR activities and surface expression,
CC recruits STK39 which mediates the inhibition (By similarity).
CC {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7,
CC ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15060842}.
CC -!- FUNCTION: [Isoform 3]: Dominant-negative regulator of the longer
CC isoform 1. Does not have kinase activity, does not directly inhibit
CC WNK4 and has no direct effect on sodium and chloride ion transport.
CC Down-regulates sodium-chloride cotransporter activity indirectly by
CC inhibiting isoform 1, it associates with isoform 1 and attenuates its
CC kinase activity. In kidney, may play an important role regulating
CC sodium and potassium balance. {ECO:0000250|UniProtKB:Q9JIH7}.
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:10660600};
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:10660600};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10660600};
CC -!- ACTIVITY REGULATION: By hypertonicity. Activation requires
CC autophosphorylation of Ser-382, that may be regulated by calcium.
CC Phosphorylation of Ser-378 also promotes increased activity.
CC {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: Interacts with SYT2 (By similarity). Interacts with WNK3 and
CC WNK4 (By similarity). Interacts with KLHL3 (PubMed:23387299,
CC PubMed:23576762). Isoform 3: Interacts with isoform 1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:23387299,
CC ECO:0000269|PubMed:23576762}.
CC -!- INTERACTION:
CC Q9H4A3; O95747: OXSR1; NbExp=8; IntAct=EBI-457907, EBI-620853;
CC Q9H4A3; P62136: PPP1CA; NbExp=2; IntAct=EBI-457907, EBI-357253;
CC Q9H4A3; Q93009: USP7; NbExp=2; IntAct=EBI-457907, EBI-302474;
CC Q9H4A3; P29101: Syt2; Xeno; NbExp=2; IntAct=EBI-457907, EBI-458017;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10660600}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Comment=WNK1 is a complex 33-exons gene, in total 9 WNK1 exons are
CC alternatively spliced, some expressed in a tissue-specific manner.
CC Additional isoforms seems to exist.;
CC Name=1 {ECO:0000269|PubMed:11571656}; Synonyms=L-WNK1;
CC IsoId=Q9H4A3-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:9205841};
CC IsoId=Q9H4A3-2; Sequence=VSP_040269, VSP_050638;
CC Name=3; Synonyms=KS-WNK1, Kidney-Specific;
CC IsoId=Q9H4A3-4; Sequence=VSP_050634, VSP_050637;
CC Name=4; Synonyms=Brain and spinal cord variant;
CC IsoId=Q9H4A3-5; Sequence=VSP_040268;
CC Name=5; Synonyms=Dorsal root ganglia and sciatic nerve variant, DRG and
CC sciatic nerve variant;
CC IsoId=Q9H4A3-6; Sequence=VSP_040267, VSP_040270;
CC Name=6;
CC IsoId=Q9H4A3-7; Sequence=VSP_040267, VSP_053767;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels observed in
CC the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-
CC specific and specifically expressed in the distal convoluted tubule
CC (DCT) and connecting tubule (CNT) of the nephron.
CC {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11571656,
CC ECO:0000269|PubMed:14645531, ECO:0000269|PubMed:22701532}.
CC -!- PTM: Autophosphorylation at Ser-382 is inhibited by intracellular
CC calcium. {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- PTM: May be O-glycosylated. {ECO:0000269|PubMed:2507249}.
CC -!- PTM: Ubiquitinated in vitro by the BCR(KLHL3) complex and in vivo by a
CC BCR(KLHL2) complex, leading to proteasomal degradation.
CC {ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23838290}.
CC -!- DISEASE: Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal
CC dominant disorder characterized by severe hypertension, hyperkalemia,
CC hyperchloremia, mild hyperchloremic metabolic acidosis in some cases,
CC and correction of physiologic abnormalities by thiazide diuretics.
CC {ECO:0000269|PubMed:11498583}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A)
CC [MIM:201300]: A form of hereditary sensory and autonomic neuropathy, a
CC genetically and clinically heterogeneous group of disorders
CC characterized by degeneration of dorsal root and autonomic ganglion
CC cells, and by sensory and/or autonomic abnormalities. HSAN2A is an
CC autosomal recessive disorder characterized by impairment of pain,
CC temperature and touch sensation, onset of symptoms in infancy or early
CC childhood, occurrence of distal extremity pathologies (paronychia,
CC whitlows, ulcers, and Charcot joints), frequent amputations, sensory
CC loss that affects all modalities of sensation (lower and upper limbs
CC and perhaps the trunk as well), absence or diminution of tendon
CC reflexes (usually in all limbs), minimal autonomic dysfunction, absence
CC of sensory nerve action potentials, and virtual absence of myelinated
CC fibers with decreased numbers of unmyelinated fibers in sural nerves.
CC {ECO:0000269|PubMed:15060842, ECO:0000269|PubMed:15911806,
CC ECO:0000269|PubMed:18521183}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Strong expression in dorsal root ganglia
CC and spinal cord.
CC -!- MISCELLANEOUS: [Isoform 3]: Kinase-defective isoform. Produced by
CC alternative promoter usage and alternative splicing. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Contains the nervous system-specific exon
CC HSN2. Produced by alternative splicing. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 5]: Contains the nervous system-specific exon
CC HSN2. Produced by alternative splicing. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Contains the nervous system-specific exon
CC HSN2. Produced by alternative splicing. {ECO:0000305}.
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:0000305|PubMed:27712055}.
CC -!- CAUTION: HSN2 was originally thought to be an intronless gene lying
CC within a WNK1 gene intron. It has been shown to be a nervous system-
CC specific exon of WNK1 included in isoform 4 and isoform 5
CC (PubMed:18521183). {ECO:0000305|PubMed:18521183}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-214 is the initiator in
CC isoform 4 and isoform 5. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF31483.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305};
CC Sequence=AAI30468.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=AAI30470.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=DAA04494.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AJ296290; CAC15059.1; -; mRNA.
DR EMBL; JQ358908; AEY99342.1; -; mRNA.
DR EMBL; FJ515833; ACS13726.1; -; Genomic_DNA.
DR EMBL; FJ515833; ACS13727.1; -; Genomic_DNA.
DR EMBL; FJ515833; ACS13728.1; -; Genomic_DNA.
DR EMBL; AC004765; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF061944; AAF31483.1; ALT_SEQ; mRNA.
DR EMBL; AB002342; BAA20802.2; -; mRNA.
DR EMBL; AY231477; AAO46160.1; -; mRNA.
DR EMBL; BC013629; AAH13629.2; -; mRNA.
DR EMBL; BC130467; AAI30468.1; ALT_SEQ; mRNA.
DR EMBL; BC130469; AAI30470.1; ALT_SEQ; mRNA.
DR EMBL; BK004108; DAA04494.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS73419.1; -. [Q9H4A3-5]
DR CCDS; CCDS8506.1; -. [Q9H4A3-1]
DR RefSeq; NP_001171914.1; NM_001184985.1. [Q9H4A3-6]
DR RefSeq; NP_055638.2; NM_014823.2.
DR RefSeq; NP_061852.3; NM_018979.3. [Q9H4A3-1]
DR RefSeq; NP_998820.3; NM_213655.4. [Q9H4A3-5]
DR RefSeq; XP_016875326.1; XM_017019837.1.
DR RefSeq; XP_016875327.1; XM_017019838.1. [Q9H4A3-2]
DR PDB; 4PWN; X-ray; 1.84 A; A=210-482.
DR PDB; 5TF9; X-ray; 2.50 A; A/B=206-483.
DR PDB; 5WDY; X-ray; 2.46 A; A/B=206-483.
DR PDB; 5WE8; X-ray; 2.01 A; A/B=206-483.
DR PDB; 6FBK; X-ray; 1.74 A; P=1247-1269.
DR PDBsum; 4PWN; -.
DR PDBsum; 5TF9; -.
DR PDBsum; 5WDY; -.
DR PDBsum; 5WE8; -.
DR PDBsum; 6FBK; -.
DR AlphaFoldDB; Q9H4A3; -.
DR BMRB; Q9H4A3; -.
DR SMR; Q9H4A3; -.
DR BioGRID; 122403; 103.
DR CORUM; Q9H4A3; -.
DR DIP; DIP-32648N; -.
DR ELM; Q9H4A3; -.
DR IntAct; Q9H4A3; 90.
DR MINT; Q9H4A3; -.
DR BindingDB; Q9H4A3; -.
DR ChEMBL; CHEMBL1075173; -.
DR GuidetoPHARMACOLOGY; 2280; -.
DR MoonDB; Q9H4A3; Predicted.
DR GlyConnect; 484; 1 O-Linked glycan.
DR GlyGen; Q9H4A3; 39 sites, 2 O-linked glycans (39 sites).
DR iPTMnet; Q9H4A3; -.
DR MetOSite; Q9H4A3; -.
DR PhosphoSitePlus; Q9H4A3; -.
DR BioMuta; WNK1; -.
DR DMDM; 296453029; -.
DR EPD; Q9H4A3; -.
DR jPOST; Q9H4A3; -.
DR MassIVE; Q9H4A3; -.
DR MaxQB; Q9H4A3; -.
DR PaxDb; Q9H4A3; -.
DR PeptideAtlas; Q9H4A3; -.
DR PRIDE; Q9H4A3; -.
DR ProteomicsDB; 80804; -. [Q9H4A3-1]
DR ProteomicsDB; 80805; -. [Q9H4A3-2]
DR ProteomicsDB; 80806; -. [Q9H4A3-4]
DR ProteomicsDB; 80807; -. [Q9H4A3-5]
DR ProteomicsDB; 80808; -. [Q9H4A3-6]
DR Antibodypedia; 22083; 617 antibodies from 42 providers.
DR DNASU; 65125; -.
DR Ensembl; ENST00000315939.11; ENSP00000313059.6; ENSG00000060237.19. [Q9H4A3-1]
DR Ensembl; ENST00000340908.9; ENSP00000341292.5; ENSG00000060237.19. [Q9H4A3-5]
DR Ensembl; ENST00000530271.6; ENSP00000433548.3; ENSG00000060237.19. [Q9H4A3-7]
DR Ensembl; ENST00000537687.5; ENSP00000444465.1; ENSG00000060237.19. [Q9H4A3-6]
DR Ensembl; ENST00000675631.1; ENSP00000502415.1; ENSG00000060237.19. [Q9H4A3-4]
DR GeneID; 65125; -.
DR KEGG; hsa:65125; -.
DR MANE-Select; ENST00000315939.11; ENSP00000313059.6; NM_018979.4; NP_061852.3.
DR UCSC; uc001qio.4; human. [Q9H4A3-1]
DR CTD; 65125; -.
DR DisGeNET; 65125; -.
DR GeneCards; WNK1; -.
DR GeneReviews; WNK1; -.
DR HGNC; HGNC:14540; WNK1.
DR HPA; ENSG00000060237; Tissue enhanced (brain).
DR MalaCards; WNK1; -.
DR MIM; 201300; phenotype.
DR MIM; 605232; gene.
DR MIM; 614492; phenotype.
DR neXtProt; NX_Q9H4A3; -.
DR OpenTargets; ENSG00000060237; -.
DR Orphanet; 970; Hereditary sensory and autonomic neuropathy type 2.
DR Orphanet; 88940; Pseudohypoaldosteronism type 2C.
DR PharmGKB; PA33782; -.
DR VEuPathDB; HostDB:ENSG00000060237; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000155474; -.
DR InParanoid; Q9H4A3; -.
DR OMA; PEPNGMT; -.
DR OrthoDB; 27514at2759; -.
DR PhylomeDB; Q9H4A3; -.
DR TreeFam; TF315363; -.
DR PathwayCommons; Q9H4A3; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q9H4A3; -.
DR SIGNOR; Q9H4A3; -.
DR BioGRID-ORCS; 65125; 563 hits in 1133 CRISPR screens.
DR ChiTaRS; WNK1; human.
DR GeneWiki; WNK1; -.
DR GenomeRNAi; 65125; -.
DR Pharos; Q9H4A3; Tchem.
DR PRO; PR:Q9H4A3; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9H4A3; protein.
DR Bgee; ENSG00000060237; Expressed in medial globus pallidus and 202 other tissues.
DR ExpressionAtlas; Q9H4A3; baseline and differential.
DR Genevisible; Q9H4A3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; IDA:UniProtKB.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0030295; F:protein kinase activator activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0004672; F:protein kinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IEA:UniProtKB-KW.
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:0055080; P:cation homeostasis; ISS:UniProtKB.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IEA:Ensembl.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL.
DR GO; GO:0038116; P:chemokine (C-C motif) ligand 21 signaling pathway; ISS:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0050801; P:ion homeostasis; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; ISS:UniProtKB.
DR GO; GO:0097022; P:lymphocyte migration into lymph node; ISS:BHF-UCL.
DR GO; GO:0033633; P:negative regulation of cell-cell adhesion mediated by integrin; IMP:BHF-UCL.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IMP:BHF-UCL.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IEA:Ensembl.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; NAS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
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; IBA:GO_Central.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IEA:Ensembl.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0055075; P:potassium ion homeostasis; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; IMP:ARUK-UCL.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IDA:ParkinsonsUK-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISS:BHF-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 promoter usage; Alternative splicing;
KW ATP-binding; Cytoplasm; Direct protein sequencing; Glycoprotein; Kinase;
KW Neurodegeneration; Neuropathy; Nucleotide-binding; Phosphoprotein;
KW Protein kinase inhibitor; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..2382
FT /note="Serine/threonine-protein kinase WNK1"
FT /id="PRO_0000086819"
FT DOMAIN 221..479
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..555
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT REGION 573..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1018..1041
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1053..1119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1457..1476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1733..1790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1866..1948
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1994..2069
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2101..2196
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2332..2352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 101..115
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..168
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 573..589
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 590..629
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 636..779
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1053..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1096..1116
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1733..1748
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1871..1885
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1886..1906
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1922..1948
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2030..2062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2133..2196
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 368
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27712055,
FT ECO:0007744|PDB:5TF9"
FT BINDING 301..304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27712055,
FT ECO:0007744|PDB:5TF9"
FT BINDING 351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:27712055,
FT ECO:0007744|PDB:5TF9"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 378
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 382
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 1261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 2002
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 2011
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2012
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2027
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 2029
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 2032
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 2121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 2270
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2286
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..407
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_050634"
FT VAR_SEQ 408..437
FT /note="FGMCMLEMATSEYPYSECQNAAQIYRRVTS -> MDIKKKDFCSVFVIINSH
FT CCCCPQKDCINE (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_050637"
FT VAR_SEQ 713
FT /note="V -> VPQSMAHPCGGTPTYPESQIFFPTIHERPVSFSPPPTCPPKVAISQR
FT RKSTSFLEAQTHHFQPLLRTVGQSLLPPGGSPTNWTPEAVVMLGTTASRVTGESCEIQV
FT HPMFEPSQVYSDYRPGLVLPEEAHYFIPQEAVYVAGVHYQARVAEQYEGIPYNSSVLSS
FT PMKQIPEQKPVQGGPTSSSVFEFPSGQAFLVGHLQNLRLDSGLGPGSPLSSISAPISTD
FT ATRLKFHPVFVPHSAPAVLTHNNESRSNCVFEFHVHTPSSSSGEGGGILPQRVYRNRQV
FT AVDLNQEELPPQSVGLHGYLQPVTEEKHNYHAPELTVSVVEPIGQNWPIGSPEYSSDSS
FT QITSSDPSDFQSPPPTGGAAAPFGSDVSMPFIHLPQTVLQESPLFFCFPQGTTSQQVLT
FT ASFSSGGSALHPQ (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:22701532"
FT /id="VSP_040267"
FT VAR_SEQ 714..1037
FT /note="AQGQSQGQPSSSSLTGVSSSQPIQHPQQQQGIQQTAPPQQTVQYSLSQTSTS
FT SEATTAQPVSQPQAPQVLPQVSAGKQLPVSQPVPTIQGEPQIPVATQPSVVPVHSGAHF
FT LPVGQPLPTPLLPQYPVSQIPISTPHVSTAQTGFSSLPITMAAGITQPLLTLASSATTA
FT AIPGVSTVVPSQLPTLLQPVTQLPSQVHPQLLQPAVQSMGIPANLGQAAEVPLSSGDVL
FT YQGFPPRLPPQYPGDSNIAPSSNVASVCIHSTVLSPPMPTEVLATPGYFPTVVQPYVES
FT NLLVPMGGVGGQVQVSQPGGSLAQAPTTSSQQAVLE -> PRRGRSMSVCVPIFLLLPL
FT CPASLPVLFHPTASTVCTSFSFPPPDCPEETFAEKLSKALESVLPMHSASQRKHRRSSL
FT PSLFVSTPQSMAHPCGGTPTYPESQIFFPTIHERPVSFSPPPTCPPKVAISQRRKSTSF
FT LEAQTHHFQPLLRTVGQSLLPPGGSPTNWTPEAVVMLGTTASRVTGESCEIQVHPMFEP
FT SQVYSDYRPGLVLPEEAHYFIPQEAVYVAGVHYQARVAEQYEGIPYNSSVLSSPMKQIP
FT EQKPVQGGPTSSSVFEFPSGQAFLVGHLQNLRLDSGLGPGSPLSSISAPISTDATRLKF
FT HPVFVPHSAPAVLTHNNESRSNCVFEFHVHTPSSSSGEGGGILPQRVYRNRQVAVDLNQ
FT EELPPQSVGLHGYLQPVTEEKHNYHAPELTVSVVEPIGQNWPIGSPEYSSDSSQITSSD
FT PSDFQSPPPTGGAAAPFGSDVSMPFIHLPQTVLQESPLFFCFPQGTTSQQVLTASFSSG
FT GSALHPQAQGQSQGQPSSSSLTGVSSSQPIQHPQQQQGIQQTAPPQQTVQYSLSQTSTS
FT SEATTAQPVSQPQAPQVLPQVSAGKQ (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_040268"
FT VAR_SEQ 740
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9205841"
FT /id="VSP_040269"
FT VAR_SEQ 792..1037
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9205841"
FT /id="VSP_050638"
FT VAR_SEQ 792..944
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_040270"
FT VAR_SEQ 2215
FT /note="G -> GCAKFNCASEQVTFKPGGRRTRFLRKMVKKVCPCNQLCR (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:22701532"
FT /id="VSP_053767"
FT VARIANT 141
FT /note="A -> T (in dbSNP:rs11554421)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041309"
FT VARIANT 149
FT /note="A -> V (in dbSNP:rs34880640)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041310"
FT VARIANT 419
FT /note="E -> Q (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041311"
FT VARIANT 509
FT /note="I -> T (in dbSNP:rs34728563)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041312"
FT VARIANT 527
FT /note="D -> G (in dbSNP:rs34408667)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041313"
FT VARIANT 665
FT /note="T -> I (in dbSNP:rs2286007)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019992"
FT VARIANT 674
FT /note="T -> A (in dbSNP:rs11833299)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041314"
FT VARIANT 823
FT /note="H -> R (in dbSNP:rs56015776)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041315"
FT VARIANT 1056
FT /note="T -> P (in dbSNP:rs956868)"
FT /evidence="ECO:0000269|PubMed:11571656,
FT ECO:0000269|PubMed:9205841, ECO:0000269|Ref.3"
FT /id="VAR_059033"
FT VARIANT 1199
FT /note="E -> G (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035640"
FT VARIANT 1506
FT /note="C -> S (in dbSNP:rs7955371)"
FT /evidence="ECO:0000269|PubMed:11571656,
FT ECO:0000269|PubMed:9205841, ECO:0000269|Ref.3"
FT /id="VAR_059034"
FT VARIANT 1546
FT /note="A -> V (in dbSNP:rs56351358)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041316"
FT VARIANT 1799
FT /note="Q -> E (in breast cancer samples; infiltrating
FT ductal carcinoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_035641"
FT VARIANT 1808
FT /note="M -> I (in dbSNP:rs12828016)"
FT /evidence="ECO:0000269|PubMed:11571656,
FT ECO:0000269|PubMed:17344846, ECO:0000269|Ref.3"
FT /id="VAR_041317"
FT VARIANT 1823
FT /note="P -> L (in dbSNP:rs17755373)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041318"
FT VARIANT 1957
FT /note="R -> H (in dbSNP:rs36083875)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041319"
FT VARIANT 2190
FT /note="S -> C (in a breast pleomorphic lobular carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041320"
FT VARIANT 2362
FT /note="F -> L (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041321"
FT VARIANT 2380
FT /note="R -> W (in dbSNP:rs56262445)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041322"
FT CONFLICT 164
FT /note="R -> S (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1836
FT /note="Missing (in Ref. 6; BAA20802)"
FT /evidence="ECO:0000305"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 220..228
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 231..240
FT /evidence="ECO:0007829|PDB:4PWN"
FT TURN 241..244
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 266..273
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:5WDY"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 309..316
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 321..340
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:4PWN"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:5WE8"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:5WE8"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 402..417
FT /evidence="ECO:0007829|PDB:4PWN"
FT TURN 421..424
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 428..435
FT /evidence="ECO:0007829|PDB:4PWN"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 442..446
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 450..459
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 470..474
FT /evidence="ECO:0007829|PDB:4PWN"
FT HELIX 477..481
FT /evidence="ECO:0007829|PDB:4PWN"
FT STRAND 1248..1251
FT /evidence="ECO:0007829|PDB:6FBK"
FT STRAND 1257..1261
FT /evidence="ECO:0007829|PDB:6FBK"
SQ SEQUENCE 2382 AA; 250794 MW; 426785F98A452A0A CRC64;
MSGGAAEKQS STPGSLFLSP PAPAPKNGSS SDSSVGEKLG AAAADAVTGR TEEYRRRRHT
MDKDSRGAAA TTTTTEHRFF RRSVICDSNA TALELPGLPL SLPQPSIPAA VPQSAPPEPH
REETVTATAT SQVAQQPPAA AAPGEQAVAG PAPSTVPSST SKDRPVSQPS LVGSKEEPPP
ARSGSGGGSA KEPQEERSQQ QDDIEELETK AVGMSNDGRF LKFDIEIGRG SFKTVYKGLD
TETTVEVAWC ELQDRKLTKS ERQRFKEEAE MLKGLQHPNI VRFYDSWEST VKGKKCIVLV
TELMTSGTLK TYLKRFKVMK IKVLRSWCRQ ILKGLQFLHT RTPPIIHRDL KCDNIFITGP
TGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD ESVDVYAFGM CMLEMATSEY
PYSECQNAAQ IYRRVTSGVK PASFDKVAIP EVKEIIEGCI RQNKDERYSI KDLLNHAFFQ
EETGVRVELA EEDDGEKIAI KLWLRIEDIK KLKGKYKDNE AIEFSFDLER DVPEDVAQEM
VESGYVCEGD HKTMAKAIKD RVSLIKRKRE QRQLVREEQE KKKQEESSLK QQVEQSSASQ
TGIKQLPSAS TGIPTASTTS ASVSTQVEPE EPEADQHQQL QYQQPSISVL SDGTVDSGQG
SSVFTESRVS SQQTVSYGSQ HEQAHSTGTV PGHIPSTVQA QSQPHGVYPP SSVAQGQSQG
QPSSSSLTGV SSSQPIQHPQ QQQGIQQTAP PQQTVQYSLS QTSTSSEATT AQPVSQPQAP
QVLPQVSAGK QLPVSQPVPT IQGEPQIPVA TQPSVVPVHS GAHFLPVGQP LPTPLLPQYP
VSQIPISTPH VSTAQTGFSS LPITMAAGIT QPLLTLASSA TTAAIPGVST VVPSQLPTLL
QPVTQLPSQV HPQLLQPAVQ SMGIPANLGQ AAEVPLSSGD VLYQGFPPRL PPQYPGDSNI
APSSNVASVC IHSTVLSPPM PTEVLATPGY FPTVVQPYVE SNLLVPMGGV GGQVQVSQPG
GSLAQAPTTS SQQAVLESTQ GVSQVAPAEP VAVAQTQATQ PTTLASSVDS AHSDVASGMS
DGNENVPSSS GRHEGRTTKR HYRKSVRSRS RHEKTSRPKL RILNVSNKGD RVVECQLETH
NRKMVTFKFD LDGDNPEEIA TIMVNNDFIL AIERESFVDQ VREIIEKADE MLSEDVSVEP
EGDQGLESLQ GKDDYGFSGS QKLEGEFKQP IPASSMPQQI GIPTSSLTQV VHSAGRRFIV
SPVPESRLRE SKVFPSEITD TVAASTAQSP GMNLSHSASS LSLQQAFSEL RRAQMTEGPN
TAPPNFSHTG PTFPVVPPFL SSIAGVPTTA AATAPVPATS SPPNDISTSV IQSEVTVPTE
EGIAGVATST GVVTSGGLPI PPVSESPVLS SVVSSITIPA VVSISTTSPS LQVPTSTSEI
VVSSTALYPS VTVSATSASA GGSTATPGPK PPAVVSQQAA GSTTVGATLT SVSTTTSFPS
TASQLCIQLS SSTSTPTLAE TVVVSAHSLD KTSHSSTTGL AFSLSAPSSS SSPGAGVSSY
ISQPGGLHPL VIPSVIASTP ILPQAAGPTS TPLLPQVPSI PPLVQPVANV PAVQQTLIHS
QPQPALLPNQ PHTHCPEVDS DTQPKAPGID DIKTLEEKLR SLFSEHSSSG AQHASVSLET
SLVIESTVTP GIPTTAVAPS KLLTSTTSTC LPPTNLPLGT VALPVTPVVT PGQVSTPVST
TTSGVKPGTA PSKPPLTKAP VLPVGTELPA GTLPSEQLPP FPGPSLTQSQ QPLEDLDAQL
RRTLSPEMIT VTSAVGPVSM AAPTAITEAG TQPQKGVSQV KEGPVLATSS GAGVFKMGRF
QVSVAADGAQ KEGKNKSEDA KSVHFESSTS ESSVLSSSSP ESTLVKPEPN GITIPGISSD
VPESAHKTTA SEAKSDTGQP TKVGRFQVTT TANKVGRFSV SKTEDKITDT KKEGPVASPP
FMDLEQAVLP AVIPKKEKPE LSEPSHLNGP SSDPEAAFLS RDVDDGSGSP HSPHQLSSKS
LPSQNLSQSL SNSFNSSYMS SDNESDIEDE DLKLELRRLR DKHLKEIQDL QSRQKHEIES
LYTKLGKVPP AVIIPPAAPL SGRRRRPTKS KGSKSSRSSS LGNKSPQLSG NLSGQSAASV
LHPQQTLHPP GNIPESGQNQ LLQPLKPSPS SDNLYSAFTS DGAISVPSLS APGQGTSSTN
TVGATVNSQA AQAQPPAMTS SRKGTFTDDL HKLVDNWARD AMNLSGRRGS KGHMNYEGPG
MARKFSAPGQ LCISMTSNLG GSAPISAASA TSLGHFTKSM CPPQQYGFPA TPFGAQWSGT
GGPAPQPLGQ FQPVGTASLQ NFNISNLQKS ISNPPGSNLR TT
