WNK1_RAT
ID WNK1_RAT Reviewed; 2126 AA.
AC Q9JIH7; Q3S2I2; Q6IFS7;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Serine/threonine-protein kinase WNK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:10828064, ECO:0000269|PubMed:12374799};
DE AltName: Full=Protein kinase lysine-deficient 1 {ECO:0000312|RGD:621141};
DE AltName: Full=Protein kinase with no lysine 1 {ECO:0000303|PubMed:10828064};
GN Name=Wnk1 {ECO:0000312|RGD:621141};
GN Synonyms=Hsn2 {ECO:0000303|PubMed:15060842}, Prkwnk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAF74258.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, SUBCELLULAR LOCATION, CAUTION, ACTIVE SITE,
RP AND MUTAGENESIS OF LYS-233; CYS-250; LYS-256; LYS-259 AND ASP-368.
RX PubMed=10828064; DOI=10.1074/jbc.275.22.16795;
RA Xu B.-E., English J.M., Wilsbacher J.L., Stippec S., Goldsmith E.J.,
RA Cobb M.H.;
RT "WNK1, a novel mammalian serine/threonine protein kinase lacking the
RT catalytic lysine in subdomain II.";
RL J. Biol. Chem. 275:16795-16801(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), ALTERNATIVE SPLICING,
RP FUNCTION (ISOFORM 5), AND SUBUNIT (ISOFORM 5).
RX PubMed=16204408; DOI=10.1152/ajprenal.00280.2005;
RA Subramanya A.R., Yang C.L., Zhu X., Ellison D.H.;
RT "Dominant-negative regulation of WNK1 by its kidney-specific kinase-
RT defective isoform.";
RL Am. J. Physiol. 290:F619-F624(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 312-2126.
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP IDENTIFICATION OF THE HSN2 EXON.
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, CAUTION, PHOSPHORYLATION
RP AT SER-378 AND SER-382, REGION, AND MUTAGENESIS OF LYS-233; CYS-250;
RP SER-378; SER-382; PHE-524 AND PHE-526.
RX PubMed=12374799; DOI=10.1074/jbc.m207917200;
RA Xu B.-E., Min X., Stippec S., Lee B.H., Goldsmith E.J., Cobb M.H.;
RT "Regulation of WNK1 by an autoinhibitory domain and autophosphorylation.";
RL J. Biol. Chem. 277:48456-48462(2002).
RN [6]
RP FUNCTION, AND INTERACTION WITH WNK3 AND WNK4.
RX PubMed=17975670; DOI=10.1172/jci32033;
RA Yang C.L., Zhu X., Ellison D.H.;
RT "The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase
RT signaling complex.";
RL J. Clin. Invest. 117:3403-3411(2007).
RN [7]
RP FUNCTION.
RX PubMed=20525693; DOI=10.1074/jbc.m110.103432;
RA Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S.,
RA Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.;
RT "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium
RT channel are regulated by multiple with no lysine (WNK) family members.";
RL J. Biol. Chem. 285:25161-25167(2010).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165; SER-172; SER-1773 AND
RP SER-1776, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 194-483 OF MUTANT ALA-382.
RX PubMed=15242606; DOI=10.1016/j.str.2004.04.014;
RA Min X., Lee B.-H., Cobb M.H., Goldsmith E.J.;
RT "Crystal structure of the kinase domain of WNK1, a kinase that causes a
RT hereditary form of hypertension.";
RL Structure 12:1303-1311(2004).
RN [10]
RP STRUCTURE BY NMR OF 480-572.
RX PubMed=23376100; DOI=10.1016/j.jmb.2013.01.031;
RA Moon T.M., Correa F., Kinch L.N., Piala A.T., Gardner K.H., Goldsmith E.J.;
RT "Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2
RT domain.";
RL J. Mol. Biol. 425:1245-1252(2013).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 194-480 OF MUTANT ALA-382,
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PHOSPHORYLATION AT
RP SER-382, AND MUTAGENESIS OF LEU-369 AND LEU-371.
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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 194-483 OF MUTANT ALA-382 IN
RP COMPLEX WITH INHIBITOR.
RX PubMed=27595330; DOI=10.1038/nchembio.2168;
RA Yamada K., Park H.M., Rigel D.F., DiPetrillo K., Whalen E.J., Anisowicz A.,
RA Beil M., Berstler J., Brocklehurst C.E., Burdick D.A., Caplan S.L.,
RA Capparelli M.P., Chen G., Chen W., Dale B., Deng L., Fu F., Hamamatsu N.,
RA Harasaki K., Herr T., Hoffmann P., Hu Q.Y., Huang W.J., Idamakanti N.,
RA Imase H., Iwaki Y., Jain M., Jeyaseelan J., Kato M., Kaushik V.K.,
RA Kohls D., Kunjathoor V., LaSala D., Lee J., Liu J., Luo Y., Ma F., Mo R.,
RA Mowbray S., Mogi M., Ossola F., Pandey P., Patel S.J., Raghavan S.,
RA Salem B., Shanado Y.H., Trakshel G.M., Turner G., Wakai H., Wang C.,
RA Weldon S., Wielicki J.B., Xie X., Xu L., Yagi Y.I., Yasoshima K., Yin J.,
RA Yowe D., Zhang J.H., Zheng G., Monovich L.;
RT "Small-molecule WNK inhibition regulates cardiovascular and renal
RT function.";
RL Nat. Chem. Biol. 12:896-898(2016).
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:Q9H4A3,
CC ECO:0000269|PubMed:10828064, ECO:0000269|PubMed:12374799,
CC ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:20525693,
CC ECO:0000269|PubMed:24803536}.
CC -!- FUNCTION: [Isoform 5]: 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:0000269|PubMed:16204408}.
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:10828064, ECO:0000269|PubMed:12374799,
CC ECO:0000269|PubMed:24803536};
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:10828064,
CC ECO:0000269|PubMed:12374799, ECO:0000269|PubMed:24803536};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10828064};
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:0000269|PubMed:10828064, ECO:0000269|PubMed:12374799,
CC ECO:0000269|PubMed:24803536}.
CC -!- SUBUNIT: Interacts with SYT2. Interacts with KLHL3, WNK3 and WNK4
CC (PubMed:17975670). Isoform 5: Interacts with isoform 1
CC (PubMed:16204408). {ECO:0000269|PubMed:15242606,
CC ECO:0000269|PubMed:16204408, ECO:0000269|PubMed:17975670}.
CC -!- INTERACTION:
CC Q9JIH7; P29101: Syt2; NbExp=9; IntAct=EBI-457953, EBI-458017;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10828064}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9JIH7-1; Sequence=Displayed;
CC Name=2; Synonyms=Brain and spinal cord variant;
CC IsoId=Q9JIH7-3; Sequence=VSP_040279;
CC Name=3; Synonyms=Dorsal root ganglia and sciatic nerve variant, DRG and
CC sciatic nerve variant;
CC IsoId=Q9JIH7-2; Sequence=VSP_040278, VSP_040280;
CC Name=4; Synonyms=KS-WNK1-long, Kidney-Specific long form
CC {ECO:0000303|PubMed:16204408};
CC IsoId=Q9JIH7-4; Sequence=VSP_058594, VSP_058596;
CC Name=5; Synonyms=KS-WNK1-short, Kidney-Specific short form
CC {ECO:0000303|PubMed:16204408};
CC IsoId=Q9JIH7-5; Sequence=VSP_058595, VSP_058596;
CC -!- PTM: Autophosphorylation at Ser-382 is inhibited by intracellular
CC calcium. {ECO:0000269|PubMed:24803536}.
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:0000250|UniProtKB:Q9H4A3}.
CC -!- MISCELLANEOUS: [Isoform 2]: This isoform which includes the HSN2 exon
CC has been identified in human and mouse. The sequence shown here is the
CC result of gene prediction. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: This isoform which includes the HSN2 exon
CC has been identified in human and mouse. The sequence shown here is the
CC result of gene prediction. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Kinase-defective isoform. Produced by
CC alternative promoter usage and alternative splicing.
CC {ECO:0000269|PubMed:16204408}.
CC -!- MISCELLANEOUS: [Isoform 5]: Kinase-defective isoform. Produced by
CC alternative promoter usage and alternative splicing.
CC {ECO:0000269|PubMed:16204408}.
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:10828064,
CC ECO:0000305|PubMed:12374799}.
CC -!- CAUTION: HSN2 was originally thought to be an intronless gene lying
CC within a WNK1 gene intron. It has been shown to be an alternative exon
CC of the WNK1 gene in other mammalian species, including human and mouse.
CC Isoforms bearing this exon (isoform 2 and isoform 3 in this entry) are
CC specifically expressed in the nervous system in these species. system.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=DAA04492.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences.; Evidence={ECO:0000305};
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; AF227741; AAF74258.1; -; mRNA.
DR EMBL; DQ177457; ABA02202.1; -; mRNA.
DR EMBL; AC106348; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BK004106; DAA04492.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001002823.2; NM_001002823.2. [Q9JIH7-2]
DR RefSeq; NP_001186024.1; NM_001199095.1. [Q9JIH7-3]
DR RefSeq; NP_446246.2; NM_053794.2. [Q9JIH7-1]
DR PDB; 2LRU; NMR; -; A=480-572.
DR PDB; 4Q2A; X-ray; 3.50 A; A=194-480.
DR PDB; 5DRB; X-ray; 1.65 A; A=194-483.
DR PDB; 5W7T; X-ray; 2.01 A; A/B=210-482.
DR PDB; 6CN9; X-ray; 1.80 A; A/B=194-483.
DR PDB; 6OL2; X-ray; 2.10 A; A=194-483.
DR PDBsum; 2LRU; -.
DR PDBsum; 4Q2A; -.
DR PDBsum; 5DRB; -.
DR PDBsum; 5W7T; -.
DR PDBsum; 6CN9; -.
DR PDBsum; 6OL2; -.
DR AlphaFoldDB; Q9JIH7; -.
DR BMRB; Q9JIH7; -.
DR SMR; Q9JIH7; -.
DR IntAct; Q9JIH7; 6.
DR CarbonylDB; Q9JIH7; -.
DR iPTMnet; Q9JIH7; -.
DR PhosphoSitePlus; Q9JIH7; -.
DR jPOST; Q9JIH7; -.
DR PaxDb; Q9JIH7; -.
DR PRIDE; Q9JIH7; -.
DR ABCD; Q9JIH7; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000013355; ENSRNOP00000013355; ENSRNOG00000009956. [Q9JIH7-2]
DR Ensembl; ENSRNOT00000013621; ENSRNOP00000013622; ENSRNOG00000009956. [Q9JIH7-3]
DR GeneID; 116477; -.
DR KEGG; rno:116477; -.
DR UCSC; RGD:621141; rat. [Q9JIH7-1]
DR CTD; 65125; -.
DR RGD; 621141; Wnk1.
DR VEuPathDB; HostDB:ENSRNOG00000009956; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000155474; -.
DR HOGENOM; CLU_000550_0_1_1; -.
DR InParanoid; Q9JIH7; -.
DR OMA; PEPNGMT; -.
DR OrthoDB; 27514at2759; -.
DR PhylomeDB; Q9JIH7; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR EvolutionaryTrace; Q9JIH7; -.
DR PRO; PR:Q9JIH7; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000009956; Expressed in Ammon's horn and 20 other tissues.
DR ExpressionAtlas; Q9JIH7; baseline and differential.
DR Genevisible; Q9JIH7; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; IMP:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IDA:RGD.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
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:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:RGD.
DR GO; GO:0055080; P:cation homeostasis; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:1990869; P:cellular response to chemokine; ISO:RGD.
DR GO; GO:0038116; P:chemokine (C-C motif) ligand 21 signaling pathway; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0033633; P:negative regulation of cell-cell adhesion mediated by integrin; ISO:RGD.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISO:RGD.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISO:RGD.
DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:RGD.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:RGD.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; ISO:RGD.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:RGD.
DR GO; GO:0055075; P:potassium ion homeostasis; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:1904062; P:regulation of cation transmembrane transport; ISO:RGD.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISO:RGD.
DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Phosphoprotein; Protein kinase inhibitor;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..2126
FT /note="Serine/threonine-protein kinase WNK1"
FT /id="PRO_0000086821"
FT DOMAIN 221..479
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 488..555
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000269|PubMed:12374799"
FT REGION 573..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1474..1507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1557..1595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1610..1695
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1709..1783
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1856..1940
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1952..1990
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2076..2097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..63
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..113
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..194
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..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..838
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..862
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1474..1503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1563..1593
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1611..1630
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1631..1654
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1676..1695
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1709..1723
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1877..1940
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1952..1988
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2083..2097
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 368
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:10828064"
FT BINDING 231
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 301..304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 378
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12374799"
FT MOD_RES 382
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12374799"
FT MOD_RES 1007
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1723
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1755
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1756
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1773
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1776
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1865
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2014
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2030
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P83741"
FT MOD_RES 2114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT VAR_SEQ 1..437
FT /note="MSDGTAEKQSGTPGFLSPPAPVPKNGSSSDSSVGEKLGAAVADSGIGRTEEY
FT RRRRHTMDKDSRGAAATTTPTEHRFFRRSVICDSNATALELPGLPLSIPQPSVPAVVPQ
FT SAPPEPHREETLTATVASQVSQQPSAAASPGEQAVVGSATATVPSSTSKDRPVSQPSLV
FT GSKEEPPPSRSGSGSGGASAKEPQEERNQQQDDIEELETKAVGMSNDGRFLKFDIEIGR
FT GSFKTVYKGLDTETTVEVAWCELQDRKLTKSERQRFKEEAEMLKGLQHPNIVRFYDSWE
FT STVKGKKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTPPIIH
FT RDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDESVDVY
FT AFGMCMLEMATSEYPYSECQNAAQIYRRVTS -> MVVCISIYFPPSFFLNSIKSVLPF
FT LMDFLKKDFCSVFVIVNSHCCCCSQKDCINE (in isoform 4)"
FT /id="VSP_058594"
FT VAR_SEQ 1..437
FT /note="MSDGTAEKQSGTPGFLSPPAPVPKNGSSSDSSVGEKLGAAVADSGIGRTEEY
FT RRRRHTMDKDSRGAAATTTPTEHRFFRRSVICDSNATALELPGLPLSIPQPSVPAVVPQ
FT SAPPEPHREETLTATVASQVSQQPSAAASPGEQAVVGSATATVPSSTSKDRPVSQPSLV
FT GSKEEPPPSRSGSGSGGASAKEPQEERNQQQDDIEELETKAVGMSNDGRFLKFDIEIGR
FT GSFKTVYKGLDTETTVEVAWCELQDRKLTKSERQRFKEEAEMLKGLQHPNIVRFYDSWE
FT STVKGKKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTPPIIH
FT RDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDESVDVY
FT AFGMCMLEMATSEYPYSECQNAAQIYRRVTS -> MDFLKKDFCSVFVIVNSHCCCCSQ
FT KDCINE (in isoform 5)"
FT /id="VSP_058595"
FT VAR_SEQ 543..2126
FT /note="Missing (in isoform 4 and isoform 5)"
FT /id="VSP_058596"
FT VAR_SEQ 714
FT /note="M -> MPRRGRSMSVCVPHLSAVPSLSRISPSAPSTPPPVLSAPLCPSLLRS
FT APEETFAEKLSKALESVLPMHSASQRKHRRSSLPSLFVTTPQSVAHPCGGTPTYPESQI
FT FFPTIHERPVSFSPPPTCPPKVAISQRRKSTSFLEAQTRHFQPLLRTVGQNHLPPGGSP
FT TNWTPEAIVMLGTTANRVNRELCEMQVQPVFETTQIYSDYRPGLVLAEEAHYFIPQETV
FT YLAGVHYQAHAAGQYEGISYNSPVLSSPMKQITEQKPVPGCPASSSVFEFPSGQAFLVG
FT HLQNLRLDSGPSPASPLSSISAPNSTDATHLKFHPVFVPHSAPAVLTHSNENRSNCVFE
FT FHAQTPSSSSGEGGGILPQRVYRNRQVAVDSSQEELSPQSVGLHCHLQPVTEEQRNNHT
FT PELTISVVEPMGQNWPVGSPEYSSDSSQITSSDISDFQSPPPTGGTAAPFGSDVSLPYI
FT RLPQTVLQESPLFFCFPQGTTSQQVLSASYSSGGSALHPQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040279"
FT VAR_SEQ 714
FT /note="M -> MPQSVAHPCGGTPTYPESQIFFPTIHERPVSFSPPPTCPPKVAISQR
FT RKSTSFLEAQTRHFQPLLRTVGQNHLPPGGSPTNWTPEAIVMLGTTANRVNRELCEMQV
FT QPVFETTQIYSDYRPGLVLAEEAHYFIPQETVYLAGVHYQAHAAGQYEGISYNSPVLSS
FT PMKQITEQKPVPGCPASSSVFEFPSGQAFLVGHLQNLRLDSGPSPASPLSSISAPNSTD
FT ATHLKFHPVFVPHSAPAVLTHSNENRSNCVFEFHAQTPSSSSGEGGGILPQRVYRNRQV
FT AVDSSQEELSPQSVGLHCHLQPVTEEQRNNHTPELTISVVEPMGQNWPVGSPEYSSDSS
FT QITSSDISDFQSPPPTGGTAAPFGSDVSLPYIRLPQTVLQESPLFFCFPQGTTSQQVLS
FT ASYSSGGSALHPQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_040278"
FT VAR_SEQ 782
FT /note="Q -> QGFPSRLPPQYPGDSNIAPSSNVASVCIHSTVLAPPPMPTEALATQG
FT YFPTVVQPYVESTPLVPMGSVGGQVQVSQPAVSLSQQPPTTSSQQAVLE (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_040280"
FT MUTAGEN 233
FT /note="K->G: Loss of kinase activity; when associated with
FT K-250."
FT /evidence="ECO:0000269|PubMed:10828064,
FT ECO:0000269|PubMed:12374799"
FT MUTAGEN 233
FT /note="K->M: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10828064,
FT ECO:0000269|PubMed:12374799"
FT MUTAGEN 250
FT /note="C->A: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:10828064,
FT ECO:0000269|PubMed:12374799"
FT MUTAGEN 250
FT /note="C->K: Reduced kinase activity. Loss of kinase
FT activity; when associated with G-233."
FT /evidence="ECO:0000269|PubMed:10828064,
FT ECO:0000269|PubMed:12374799"
FT MUTAGEN 256
FT /note="K->M: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:10828064"
FT MUTAGEN 259
FT /note="K->M: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:10828064"
FT MUTAGEN 368
FT /note="D->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10828064"
FT MUTAGEN 369
FT /note="L->F: Decreased calcium-dependent inhibition of
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:24803536"
FT MUTAGEN 371
FT /note="L->F: Decreased calcium-dependent inhibition of
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:24803536"
FT MUTAGEN 378
FT /note="S->A: Reduced kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT MUTAGEN 378
FT /note="S->D: Increased kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT MUTAGEN 382
FT /note="S->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT MUTAGEN 382
FT /note="S->D: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT MUTAGEN 524
FT /note="F->A: Reduced ability of autoinhibitory domain to
FT regulate kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT MUTAGEN 526
FT /note="F->A: Reduced ability of autoinhibitory domain to
FT regulate kinase activity."
FT /evidence="ECO:0000269|PubMed:12374799"
FT CONFLICT 1179
FT /note="S -> F (in Ref. 1; AAF74258)"
FT /evidence="ECO:0000305"
FT CONFLICT 1950
FT /note="V -> I (in Ref. 1; AAF74258)"
FT /evidence="ECO:0000305"
FT CONFLICT 2120
FT /note="G -> S (in Ref. 1; AAF74258)"
FT /evidence="ECO:0000305"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 220..229
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 231..240
FT /evidence="ECO:0007829|PDB:5DRB"
FT TURN 241..243
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 246..252
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:6CN9"
FT HELIX 259..273
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 309..316
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 321..339
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 371..374
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:5W7T"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 402..417
FT /evidence="ECO:0007829|PDB:5DRB"
FT TURN 421..424
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 428..435
FT /evidence="ECO:0007829|PDB:5DRB"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 442..446
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 450..459
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 470..474
FT /evidence="ECO:0007829|PDB:5DRB"
FT HELIX 477..479
FT /evidence="ECO:0007829|PDB:5DRB"
FT STRAND 484..491
FT /evidence="ECO:0007829|PDB:2LRU"
FT STRAND 498..507
FT /evidence="ECO:0007829|PDB:2LRU"
FT STRAND 511..515
FT /evidence="ECO:0007829|PDB:2LRU"
FT STRAND 521..527
FT /evidence="ECO:0007829|PDB:2LRU"
FT TURN 528..530
FT /evidence="ECO:0007829|PDB:2LRU"
FT HELIX 533..542
FT /evidence="ECO:0007829|PDB:2LRU"
FT HELIX 548..550
FT /evidence="ECO:0007829|PDB:2LRU"
FT HELIX 551..568
FT /evidence="ECO:0007829|PDB:2LRU"
SQ SEQUENCE 2126 AA; 225112 MW; 89AC72F9CC8B07DF CRC64;
MSDGTAEKQS GTPGFLSPPA PVPKNGSSSD SSVGEKLGAA VADSGIGRTE EYRRRRHTMD
KDSRGAAATT TPTEHRFFRR SVICDSNATA LELPGLPLSI PQPSVPAVVP QSAPPEPHRE
ETLTATVASQ VSQQPSAAAS PGEQAVVGSA TATVPSSTSK DRPVSQPSLV GSKEEPPPSR
SGSGSGGASA KEPQEERNQQ 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 KRKQEESSFK QQNEQQASVS
QAGIQPLSVA STGIPTAPTT SASVSTQVEP EEPEADQHQQ LQYQQPSISV LSDGTVDSGQ
GSSVFTESRV SSQQTVSYGS QHEQAHSIGT APGHTVSSIQ AQSQPHGVYP PSSMAQGQNQ
GQPSSSLAGV LSSQPVQHPQ QQGIQPTVPP QQAVQYSLPQ AASSSEGTVQ PVSQPQVSAG
TQSSTQGVSQ AAPPEQTPIT QSQPTQPVPL VSSVDSAHSD VASGMSDGNE NAPSSSGRHE
GRTTKRHYRK SVRSRSRHEK TSRPKLRILN VSNKGDRVVE CQLETHNRKM VTFKFDLDGD
NPEEIATIMV NNDFILAIER ESFVAQVREI IEKADEMLSE DVSVEPEGDQ GLESLQGKDD
YGFPGSQKLE GEFKQPIAVS SMPQQIGVPT SSLTQVVHSA GRRFIVSPVP ESRLRESKIF
TSEIPDPVAA STSQGPGMNL SHSASSLSLQ QAFSELKHGQ MTEGPNTAPP NFNHPGPTFS
PFLTSIAGVQ TVAASTPSVS VPITSSPLND ISTSVMQSEG ALPTDKGIGG VTTSTGVVAS
GGLTTLSVSE TPTLSSAVSS STAPAVVTVS TTSQPVQAST SGSIASSTGS FPSGTFSTTT
GTTVSSVAVP NAKPPTVLLQ QVAGNTAGVA IVTSVSTTTP FPAMASQPSL PLGSSTSAPT
LAETVVVSAH SLDKASHSST AGLGLSFCAP SSSSSSGTAV SSSVSQPGIV HPLVISSAIA
STPVLPQPAV PTSTPLLPQV PNIPPLVQPV ANVPAVQQTL IHSQPQPALL PNQPHTHCPE
MDADTQSKAP GIDDIKTLEE KLRSLFSEHS SSGTQHASVS LETPLVVETV TPGIPTTAVA
PSKLMTSTTS TCLPPTNLPL GTAGMPVMPV GTPGQVSTPG THASAPASTA TGAKPGTTPP
KPSLTKTVVP PVGTELSAGT VPCEQLPPFP GPSLIQTQQP LEDLDAQLRR TLSPETIPVT
PAVGPLSTMS STAVTEAGSQ PQKDGTEVHV TASSSGAGVV KMGRFQVSVT MDDAQKERKN
RSEDTKSVHF ESSTSESSVL SSSSPESTLV KPEPNGITVS GISLDVPDST HRTPTPEAKS
ETGQPTKVGR FQVTTTANKV GRFSVSRTED KVTELKKEGP VTSPFRDSEQ TVIPAAIPKK
EKPELAEPSH LNGPSSDLEA AFLSRGGEDG SGSPHSPPHL CSKSLPIQTL SQSLSNSFNS
SYMSSDNESD IEDEDLRLEL RRLREKHLKE IQDLQSRQKH EIESLYTKLG KVPPAVIIPP
AAPLSGRRRR PTKSKGSKSS RSSSLGNKSP QLSGNLSGQS GTSVLNPQQT LHPPGNTPET
GHNQLLQPLK PSPSSDNLYS AFTSDGAISV PSLSAPGQGT SSTNTVGGTV SSQAAQAQPP
AMTSSRKGTF TDDLHKLVDN WARDAMNLSG RRGSKGHMNY EGPGMARKFS APGQLCISMT
SNMGGSTPIS AASATSLGHF TKSMCPPQQY GFPAAPFGTQ WSGTGGPAPQ PLGQFQPVGT
TSLQNFNISN LQKSISNPPG SNLRTT
