ID WNK1_MOUSE Reviewed; 2377 AA.
AC P83741; A6H6V1; B2RRJ7; B7ZNJ4; Q3UZP3; Q6A083; Q6IFS6; Q6VYA0;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 27-MAR-2024, entry version 186.
DE RecName: Full=Serine/threonine-protein kinase WNK1 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9H4A3};
DE AltName: Full=Protein kinase lysine-deficient 1 {ECO:0000312|MGI:MGI:2442092};
DE AltName: Full=Protein kinase with no lysine 1 {ECO:0000303|PubMed:14514722};
GN Name=Wnk1 {ECO:0000303|PubMed:14514722, ECO:0000312|MGI:MGI:2442092};
GN Synonyms=Hsn2 {ECO:0000303|PubMed:15060842},
GN Prkwnk1 {ECO:0000312|MGI:MGI:2442092};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 7), TISSUE SPECIFICITY, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=C57BL/6J;
RX PubMed=14514722; DOI=10.1097/01.asn.0000089830.97681.3b;
RA O'Reilly M., Marshall E., Speirs H.J., Brown R.W.;
RT "WNK1, a gene within a novel blood pressure control pathway, tissue-
RT specifically generates radically different isoforms with and without a
RT kinase domain.";
RL J. Am. Soc. Nephrol. 14:2447-2456(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RC TISSUE=Embryonic tail;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5), AND PARTIAL
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2/3).
RC STRAIN=C57BL/6J {ECO:0000269|PubMed:15489334};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH56761.1};
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-578.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=12671053; DOI=10.1172/jci17443;
RA Yang C.-L., Angell J., Mitchell R., Ellison D.H.;
RT "WNK kinases regulate thiazide-sensitive Na-Cl cotransport.";
RL J. Clin. Invest. 111:1039-1045(2003).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12522152; DOI=10.1073/pnas.242728499;
RA Choate K.A., Kahle K.T., Wilson F.H., Nelson-Williams C., Lifton R.P.;
RT "WNK1, a kinase mutated in inherited hypertension with hyperkalemia,
RT localizes to diverse Cl- -transporting epithelia.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:663-668(2003).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14610273; DOI=10.1073/pnas.2336103100;
RA Zambrowicz B.P., Abuin A., Ramirez-Solis R., Richter L.J., Piggott J.,
RA BeltrandelRio H., Buxton E.C., Edwards J., Finch R.A., Friddle C.J.,
RA Gupta A., Hansen G., Hu Y., Huang W., Jaing C., Key B.W. Jr., Kipp P.,
RA Kohlhauff B., Ma Z.Q., Markesich D., Payne R., Potter D.G., Qian N.,
RA Shaw J., Schrick J., Shi Z.Z., Sparks M.J., Van Sligtenhorst I., Vogel P.,
RA Walke W., Xu N., Zhu Q., Person C., Sands A.T.;
RT "Wnk1 kinase deficiency lowers blood pressure in mice: a gene-trap screen
RT to identify potential targets for therapeutic intervention.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14109-14114(2003).
RN [10]
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 [11]
RP ALTERNATIVE SPLICING.
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2027, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORMS 2 AND 3), AND TISSUE SPECIFICITY.
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 [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19644017; DOI=10.2353/ajpath.2009.090094;
RA Xie J., Wu T., Xu K., Huang I.K., Cleaver O., Huang C.L.;
RT "Endothelial-specific expression of WNK1 kinase is essential for
RT angiogenesis and heart development in mice.";
RL Am. J. Pathol. 175:1315-1327(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-17; SER-2027; SER-2265 AND
RP SER-2281, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION (ISOFORM 7).
RX PubMed=21131289; DOI=10.1093/hmg/ddq525;
RA Liu Z., Xie J., Wu T., Truong T., Auchus R.J., Huang C.L.;
RT "Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1
RT revealed by gene disruption and transgenic mouse models.";
RL Hum. Mol. Genet. 20:855-866(2011).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-368.
RX PubMed=21317537; DOI=10.1172/jci43475;
RA Yang D., Li Q., So I., Huang C.L., Ando H., Mizutani A., Seki G.,
RA Mikoshiba K., Thomas P.J., Muallem S.;
RT "IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK
RT kinase pathway.";
RL J. Clin. Invest. 121:956-965(2011).
RN [18]
RP FUNCTION.
RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047;
RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H.,
RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K.,
RA Muallem S.;
RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
RT epithelial transport in mice.";
RL Gastroenterology 145:232-241(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase component of the WNK1-
CC SPAK/OSR1 kinase cascade, which acts as a key regulator of blood
CC pressure and regulatory volume increase by promoting ion influx
CC (PubMed:12671053, PubMed:14610273). WNK1 mediates regulatory volume
CC increase in response to hyperosmotic stress by acting as a molecular
CC crowding sensor, which senses cell shrinkage and mediates formation of
CC a membraneless compartment by undergoing liquid-liquid phase separation
CC (By similarity). The membraneless compartment concentrates WNK1 with
CC its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent
CC phosphorylation and activation of downstream kinases OXSR1/OSR1 and
CC STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and
CC STK39/SPAK catalyze phosphorylation of ion cotransporters
CC SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating
CC their activity (By similarity). Phosphorylation of Na-K-Cl
CC cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation
CC and ion influx; simultaneously, phosphorylation of K-Cl cotransporters
CC SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion
CC efflux (By similarity). Also acts as a regulator of angiogenesis in
CC endothelial cells (PubMed:19644017). Also acts independently of the
CC WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other
CC substrates, such as SYT2, PCF11 and NEDD4L (By similarity). Mediates
CC phosphorylation of SYT2, regulating SYT2 association with phospholipids
CC and membrane-binding (By similarity). Regulates mRNA export in the
CC nucleus by mediating phosphorylation of PCF11, thereby decreasing the
CC association between PCF11 and POLR2A/RNA polymerase II and promoting
CC mRNA export to the cytoplasm (By similarity). Acts as a negative
CC regulator of autophagy (By similarity). Required for the abscission
CC step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade
CC (By similarity). WNK1 may also play a role in actin cytoskeletal
CC reorganization (By similarity). Also acts as a scaffold protein
CC independently of its protein kinase activity: negatively regulates cell
CC membrane localization of various transporters and channels, such as
CC SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (PubMed:21317537,
CC PubMed:23542070). Involved in the regulation of epithelial Na(+)
CC channel (ENaC) by promoting activation of SGK1 in a kinase-independent
CC manner: probably acts as a scaffold protein that promotes the
CC recruitment of SGK1 to the mTORC2 complex in response to chloride,
CC leading to mTORC2-dependent phosphorylation and activation of SGK1 (By
CC similarity). Acts as an assembly factor for the ER membrane protein
CC complex independently of its protein kinase activity: associates with
CC EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents
CC EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2
CC stabilization (By similarity). {ECO:0000250|UniProtKB:Q9H4A3,
CC ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:12671053,
CC ECO:0000269|PubMed:14610273, ECO:0000269|PubMed:19644017,
CC ECO:0000269|PubMed:21317537, ECO:0000269|PubMed:23542070}.
CC -!- FUNCTION: [Isoform 7]: Kinase-defective isoform specifically expressed
CC in kidney, which acts as a dominant-negative regulator of the longer
CC isoform 1 (PubMed:21131289). Does not directly inhibit WNK4 and has no
CC direct effect on sodium and chloride ion transport (By similarity).
CC Down-regulates sodium-chloride cotransporter activity indirectly by
CC inhibiting isoform 1, it associates with isoform 1 and attenuates its
CC kinase activity (By similarity). In kidney, may play an important role
CC regulating sodium and potassium balance (By similarity).
CC {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:21131289}.
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: Activated in response to hyperosmotic stress: cell
CC shrinkage promotes formation of a membraneless compartment that
CC concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK (By
CC similarity). Activation requires autophosphorylation of Ser-382 and, to
CC a lower extent, Ser-378 (By similarity). Autophosphorylation and
CC subsequent activation is inhibited by increases in intracellular ionic
CC strength: Cl(-) potently inhibits WNK1 kinase activity via direct
CC binding (By similarity). Also inhibited by K(+) ions (By similarity).
CC {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: Interacts with WNK3. Interacts with WNK4; inhibiting the
CC activity of WNK4 (By similarity). Interacts with SGK1; promoting its
CC activation. Associates with the mTORC2 complex (By similarity).
CC Interacts with UVRAG (By similarity). {ECO:0000250|UniProtKB:Q9H4A3,
CC ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: [Isoform 7]: Interacts with isoform 1; inhibiting isoform 1
CC activity. {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11498583,
CC ECO:0000269|PubMed:14610273}. Nucleus {ECO:0000250|UniProtKB:Q9H4A3}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:Q9H4A3}.
CC Note=Mediates formation and localizes to cytoplasmic membraneless
CC compartment in response to hyperosmotic stress (By similarity). Also
CC localizes to the nucleus (By similarity). Localizes to the mitotic
CC spindle during mitosis (By similarity). {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=P83741-1; Sequence=Displayed;
CC Name=2; Synonyms=Brain and spinal cord variant;
CC IsoId=P83741-2; Sequence=VSP_040271;
CC Name=3; Synonyms=Dorsal root ganglia and sciatic nerve variant, DRG and
CC sciatic nerve variant;
CC IsoId=P83741-3; Sequence=VSP_040272;
CC Name=4;
CC IsoId=P83741-4; Sequence=VSP_040273;
CC Name=5;
CC IsoId=P83741-5; Sequence=VSP_040274, VSP_040277;
CC Name=6;
CC IsoId=P83741-6; Sequence=VSP_040275, VSP_040276;
CC Name=7; Synonyms=KS-WNK1 {ECO:0000303|PubMed:21131289}, Kidney-Specific
CC {ECO:0000303|PubMed:16204408};
CC IsoId=P83741-7; Sequence=VSP_058592, VSP_058593;
CC -!- TISSUE SPECIFICITY: Widely expressed in both adult and embryonic
CC tissue, with highest levels observed in the testis and lower levels in
CC heart, lung, kidney, placenta, brain and skeletal muscle
CC (PubMed:11498583, PubMed:14514722, PubMed:12522152). Expressed in
CC pancreatic duct (PubMed:21317537). Two isoforms are expressed in heart,
CC a single shorter isoform in the kidney (PubMed:14514722). Locates to
CC the distal convoluted tubule, the medullary collecting duct and the
CC cortical collecting duct of the kidney (PubMed:14514722).
CC {ECO:0000269|PubMed:11498583, ECO:0000269|PubMed:12522152,
CC ECO:0000269|PubMed:14514722, ECO:0000269|PubMed:21317537}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Restricted to the nervous system,
CC expressed preferentially in sensory neurons than in motor neurons and
CC in general more abundant in axons than in cell bodies (at protein
CC level) (PubMed:18521183). In the DRG, predominantly expressed in the
CC satellite cells that envelop sensory neurons, but low expression also
CC observed in the cell bodies of neurons (at protein level)
CC (PubMed:18521183). In the sciatic nerve, expressed in the Schwann cells
CC that surround axons and in a mosaic distribution of axons (at protein
CC level) (PubMed:18521183). In the spinal cord, expressed in superficial
CC layers (LI and LII), as well as in the fibers of the Lissauer tract (at
CC protein level) (PubMed:18521183). Also detected in the axon fibers of
CC dorsolateral funiculus and lateral funiculus (at protein level)
CC (PubMed:18521183). {ECO:0000269|PubMed:18521183}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Restricted to the nervous system,
CC expressed preferentially in sensory neurons than in motor neurons and
CC in general more abundant in axons than in cell bodies (at protein
CC level) (PubMed:18521183). In the DRG, predominantly expressed in the
CC satellite cells that envelop sensory neurons, but low expression also
CC observed in the cell bodies of neurons (at protein level)
CC (PubMed:18521183). In the sciatic nerve, expressed in the Schwann cells
CC that surround axons and in a mosaic distribution of axons (at protein
CC level) (PubMed:18521183). In the spinal cord, expressed in superficial
CC layers (LI and LII), as well as in the fibers of the Lissauer tract (at
CC protein level) (PubMed:18521183). Also detected in the axon fibers of
CC dorsolateral funiculus and lateral funiculus (at protein level)
CC (PubMed:18521183). {ECO:0000269|PubMed:18521183}.
CC -!- DOMAIN: The RFXV motifs mediate recognition with downstream kinases
CC OXSR1/OSR1 and STK39/SPAK. {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- DOMAIN: Disordered regions undergo liquid-liquid phase separation
CC (LLPS) for the formation of a cytoplasmic membraneless compartment that
CC concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK.
CC {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- PTM: Autophosphorylated at Ser-378 and Ser-382, promoting its activity
CC (By similarity). Autophosphorylation at Ser-382 is inhibited by
CC intracellular calcium (By similarity). Phosphorylation at Thr-58
CC increases ability to activate SGK1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL3) complex, leading to its
CC degradation (By similarity). Also ubiquitinated by the BCR(KLHL2)
CC complex (By similarity). {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- PTM: May be O-glycosylated. {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality before day 13 of gestation
CC (PubMed:14610273, PubMed:19644017). Embryos show cardiovascular
CC developmental defects: the developing heart has smaller chambers and
CC reduced myocardial trabeculation at E10.5 (PubMed:19644017). Yolk sac
CC vessels in the E10.5 null mutant fail to remodel into a network of
CC large and small vessels and embryonic vessels show defective
CC angiogenesis that involves both arteries and veins (PubMed:19644017).
CC Hypomorphic mice display a significant decrease in blood pressure
CC (PubMed:14610273). Conditional deletion in endothelial cells leads to
CC cardiovascular developmental defects, leading to embryonic lethality
CC (PubMed:19644017). {ECO:0000269|PubMed:14610273,
CC ECO:0000269|PubMed:19644017}.
CC -!- MISCELLANEOUS: [Isoform 6]: May be due to intron retention.
CC {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:0000250|UniProtKB:Q9H4A3}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-214 is the initiator.
CC {ECO:0000305}.
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 2 and isoform 3
CC (PubMed:18521183). {ECO:0000305|PubMed:18521183}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI46010.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=AAI46012.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=BAD32213.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=DAA04493.1; Type=Erroneous gene model prediction; Note=Includes 3' and 3' intronic sequences.; Evidence={ECO:0000305};
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DR EMBL; AY309076; AAQ77243.1; -; mRNA.
DR EMBL; AY319934; AAQ84611.1; -; mRNA.
DR EMBL; AK172935; BAD32213.1; ALT_INIT; mRNA.
DR EMBL; AC113092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117667; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056761; AAH56761.1; -; mRNA.
DR EMBL; BC138445; AAI38446.1; -; mRNA.
DR EMBL; BC145282; AAI45283.1; -; mRNA.
DR EMBL; BC146009; AAI46010.1; ALT_SEQ; mRNA.
DR EMBL; BC146011; AAI46012.1; ALT_SEQ; mRNA.
DR EMBL; BC171955; AAI71955.1; -; mRNA.
DR EMBL; AK133738; BAE21813.1; -; mRNA.
DR EMBL; BK004107; DAA04493.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS20478.1; -. [P83741-1]
DR CCDS; CCDS51888.1; -. [P83741-5]
DR CCDS; CCDS57444.1; -. [P83741-3]
DR CCDS; CCDS57445.1; -. [P83741-2]
DR CCDS; CCDS85147.1; -. [P83741-4]
DR RefSeq; NP_001171949.1; NM_001185020.1. [P83741-4]
DR RefSeq; NP_001171950.1; NM_001185021.1. [P83741-5]
DR RefSeq; NP_001186012.1; NM_001199083.1. [P83741-2]
DR RefSeq; NP_001186013.1; NM_001199084.1. [P83741-3]
DR RefSeq; NP_941992.2; NM_198703.3. [P83741-1]
DR RefSeq; XP_017177038.1; XM_017321549.1. [P83741-1]
DR RefSeq; XP_017177043.1; XM_017321554.1. [P83741-5]
DR RefSeq; XP_017177046.1; XM_017321557.1. [P83741-4]
DR AlphaFoldDB; P83741; -.
DR BMRB; P83741; -.
DR SMR; P83741; -.
DR BioGRID; 231244; 20.
DR IntAct; P83741; 1.
DR MINT; P83741; -.
DR STRING; 10090.ENSMUSP00000086017; -.
DR ChEMBL; CHEMBL2176799; -.
DR GlyConnect; 2429; 1 N-Linked glycan (1 site). [P83741-2]
DR GlyGen; P83741; 40 sites, 1 O-linked glycan (40 sites).
DR iPTMnet; P83741; -.
DR PhosphoSitePlus; P83741; -.
DR SwissPalm; P83741; -.
DR EPD; P83741; -.
DR jPOST; P83741; -.
DR MaxQB; P83741; -.
DR PaxDb; 10090-ENSMUSP00000063001; -.
DR PeptideAtlas; P83741; -.
DR ProteomicsDB; 299987; -. [P83741-1]
DR ProteomicsDB; 299988; -. [P83741-2]
DR ProteomicsDB; 299989; -. [P83741-3]
DR ProteomicsDB; 299990; -. [P83741-4]
DR ProteomicsDB; 299991; -. [P83741-5]
DR ProteomicsDB; 299992; -. [P83741-6]
DR ProteomicsDB; 299993; -. [P83741-7]
DR Pumba; P83741; -.
DR Antibodypedia; 22083; 683 antibodies from 42 providers.
DR DNASU; 232341; -.
DR Ensembl; ENSMUST00000060043.13; ENSMUSP00000063001.7; ENSMUSG00000045962.17. [P83741-1]
DR Ensembl; ENSMUST00000088644.13; ENSMUSP00000086017.7; ENSMUSG00000045962.17. [P83741-3]
DR Ensembl; ENSMUST00000088646.12; ENSMUSP00000086019.6; ENSMUSG00000045962.17. [P83741-5]
DR Ensembl; ENSMUST00000177761.8; ENSMUSP00000136777.2; ENSMUSG00000045962.17. [P83741-2]
DR Ensembl; ENSMUST00000203030.3; ENSMUSP00000145304.2; ENSMUSG00000045962.17. [P83741-4]
DR GeneID; 232341; -.
DR KEGG; mmu:232341; -.
DR UCSC; uc009dmt.2; mouse. [P83741-1]
DR UCSC; uc009dmu.2; mouse. [P83741-5]
DR UCSC; uc009dmv.2; mouse. [P83741-6]
DR UCSC; uc012ers.1; mouse. [P83741-3]
DR UCSC; uc012ert.1; mouse. [P83741-2]
DR UCSC; uc012eru.1; mouse. [P83741-4]
DR AGR; MGI:2442092; -.
DR CTD; 65125; -.
DR MGI; MGI:2442092; Wnk1.
DR VEuPathDB; HostDB:ENSMUSG00000045962; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000155474; -.
DR HOGENOM; CLU_000550_0_0_1; -.
DR InParanoid; P83741; -.
DR OMA; PEPNGMT; -.
DR OrthoDB; 5478852at2759; -.
DR PhylomeDB; P83741; -.
DR TreeFam; TF315363; -.
DR BioGRID-ORCS; 232341; 21 hits in 85 CRISPR screens.
DR ChiTaRS; Wnk1; mouse.
DR PRO; PR:P83741; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P83741; Protein.
DR Bgee; ENSMUSG00000045962; Expressed in endothelial cell of lymphatic vessel and 291 other cell types or tissues.
DR ExpressionAtlas; P83741; baseline and differential.
DR Genevisible; P83741; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0140693; F:molecular condensate scaffold activity; ISS:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; ISS:UniProtKB.
DR GO; GO:0019870; F:potassium channel inhibitor activity; ISO:MGI.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISO:MGI.
DR GO; GO:0006884; P:cell volume homeostasis; ISS:UniProtKB.
DR GO; GO:0071474; P:cellular hyperosmotic response; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI.
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; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0030644; P:intracellular chloride ion homeostasis; IGI:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0097022; P:lymphocyte migration into lymph node; IMP:BHF-UCL.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:MGI.
DR GO; GO:0055080; P:monoatomic cation homeostasis; IDA:GO_Central.
DR GO; GO:0050801; P:monoatomic ion homeostasis; IBA:GO_Central.
DR GO; GO:0006811; P:monoatomic ion transport; IDA:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0033633; P:negative regulation of cell-cell adhesion mediated by integrin; ISO:MGI.
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; ISO:MGI.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IMP:MGI.
DR GO; GO:1903077; P:negative regulation of protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0140694; P:non-membrane-bounded organelle assembly; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:1903490; P:positive regulation of mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:1903288; P:positive regulation of potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:MGI.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:MGI.
DR GO; GO:1904595; P:positive regulation of termination of RNA polymerase II transcription; ISS:UniProtKB.
DR GO; GO:0055075; P:potassium ion homeostasis; IMP:MGI.
DR GO; GO:0045050; P:protein insertion into ER membrane by stop-transfer membrane-anchor sequence; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
DR GO; GO:1904062; P:regulation of monoatomic cation transmembrane transport; ISO:MGI.
DR GO; GO:0010793; P:regulation of mRNA export from nucleus; ISS:UniProtKB.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IMP:MGI.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:MGI.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:BHF-UCL.
DR CDD; cd14030; STKc_WNK1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024678; Kinase_OSR1/WNK_CCT.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR13902; SERINE/THREONINE-PROTEIN KINASE WNK WITH NO LYSINE -RELATED; 1.
DR PANTHER; PTHR13902:SF46; SERINE_THREONINE-PROTEIN KINASE WNK1; 1.
DR Pfam; PF12202; OSR1_C; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Chloride; Cytoplasm; Cytoskeleton;
KW Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..2377
FT /note="Serine/threonine-protein kinase WNK1"
FT /id="PRO_0000086820"
FT DOMAIN 221..479
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..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..782
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..639
FT /note="Interaction with KLHL3"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT REGION 1013..1114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1726..1760
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1818..1847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1860..1945
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1959..1984
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1989..2008
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2015..2064
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2107..2191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2203..2239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2236..2256
FT /note="Amphipathic alpha-helix"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT REGION 2325..2344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1252..1255
FT /note="RFXV motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOTIF 1854..1857
FT /note="RFXV motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOTIF 1940..1943
FT /note="RFXV motif 3"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOTIF 1952..1955
FT /note="RFXV motif 4"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
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..782
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1013..1087
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1091..1111
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1818..1843
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1861..1880
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1881..1904
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1959..1973
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2033..2057
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2128..2191
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:0000250|UniProtKB:Q9H4A3"
FT BINDING 283
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 299
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
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 BINDING 369
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 371
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 17
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
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 1256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1843
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 1973
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2006
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2007
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2022
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2024
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2027
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 2116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 2367
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT VAR_SEQ 1..437
FT /note="MSDGAAEKQSGTPGFLTPPAPVPKNGSSSDSSVGEKLGATVADSGVGRTEEY
FT RRRRHTMDKDSRGAAATTTPTEHRFFRRSVICDSNATALELPGLPLSIPQPSVPAVVPQ
FT SAPPEPHREETLTATVASQVSQQPSAAASPGEQAVVGSATTTVPSSTSKDRPVSQPSLV
FT GSKEEPPPSRSGSGSGGASAKEAQEDRSQQQDDIEELETKAVGMSNDGRFLKFDIEIGR
FT GSFKTVYKGLDTETTVEVAWCELQDRKLTKSERQRFKEEAEMLKGLQHPNIVRFYDSWE
FT STVKGKKCIVLVTELMTSGTLKTYLKRFKVMKIKVLRSWCRQILKGLQFLHTRTPPIIH
FT RDLKCDNIFITGPTGSVKIGDLGLATLKRASFAKSVIGTPEFMAPEMYEEKYDESVDVY
FT AFGMCMLEMATSEYPYSECQNAAQIYRRVTS -> MDFMKKDFCSVFVIVNSHCCCCSQ
FT KDCINE (in isoform 7)"
FT /id="VSP_058592"
FT VAR_SEQ 543..2377
FT /note="Missing (in isoform 7)"
FT /id="VSP_058593"
FT VAR_SEQ 715..1032
FT /note="AQGQNQGQPSSSLAGVLSSQPIQHPQQQGIQPTVPSQQAVQYSLPQAASSSE
FT GTTAQPVSQPQVSAGTQLPVSQTVATVQGEPHIPVSTQPSVVPVHSGAHFLPMGQPIPT
FT SLLPQYPVSQIPISTPHVSTAQTGFSSVPITMAAGINQPLLTLASSATASSIPGGSPVV
FT PNQLPTLLQPVNQLQSQVHPQLLQPTTVQSIGIPANLGQAAEGPLPSGDVLYQGFPSRL
FT PPQYPGDSNIAPSSNVASVCIHSTVLAPPSMPTEALATQGYFPTVVQPYVESTPLVPMG
FT SVGGQVQVSQPAVSLTQQPPTTSSQQAVLE -> PRRGRSMSVCVPHLSAVPSLSRISP
FT SAPSTPPPVLSAPLCPSLLRTAPEETFAEKLSKALESVLPMHSASQRKHRRSSLPSLFV
FT TTPQSMAHPCGGTPTYPESQIFFPTIHERPVSFSPPPTCPPKVAISQRRKSTSFLEAQT
FT RHFQPLLRTVGQNHLPPGSSPTNWTPEAIVMLGATANRVNRELCEMQVQPVFEPTQIYS
FT DYRPGLVLAEEAHYFIPQETVYLAGVHYQAQVAGQYEGISYNSPVLSSPMKQISEQKPV
FT PGGPASSSVFEFPSGQAFLVGHLQNLRLDSGPSPASPLSSISAPNSTDATHLKFHPVFV
FT PHSAPAVLTNSNENRSNCVFEFHAQTPSSSGEGGGILPQRVYRNRQVAVDSNQEELSPQ
FT SVGLHCHLQPVTEEQRNNHAPELTISVVEPMGQIWPIGSPEYSSDSSQITSSDLSDFQS
FT PPPTGGTAAPFGSDVSLPFIRLPQTVLQESPLFFCFPQGTTSQQVLSASYSSGGSTLHP
FT QAQGQNQGQPSSSLAGVLSSQPIQHPQQQGIQPTVPSQQAVQYSLPQAASSSEGTTAQP
FT VSQPQVSAGTQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040271"
FT VAR_SEQ 715..936
FT /note="AQGQNQGQPSSSLAGVLSSQPIQHPQQQGIQPTVPSQQAVQYSLPQAASSSE
FT GTTAQPVSQPQVSAGTQLPVSQTVATVQGEPHIPVSTQPSVVPVHSGAHFLPMGQPIPT
FT SLLPQYPVSQIPISTPHVSTAQTGFSSVPITMAAGINQPLLTLASSATASSIPGGSPVV
FT PNQLPTLLQPVNQLQSQVHPQLLQPTTVQSIGIPANLGQAAEGPLPSGDVLY -> PQS
FT MAHPCGGTPTYPESQIFFPTIHERPVSFSPPPTCPPKVAISQRRKSTSFLEAQTRHFQP
FT LLRTVGQNHLPPGSSPTNWTPEAIVMLGATANRVNRELCEMQVQPVFEPTQIYSDYRPG
FT LVLAEEAHYFIPQETVYLAGVHYQAQVAGQYEGISYNSPVLSSPMKQISEQKPVPGGPA
FT SSSVFEFPSGQAFLVGHLQNLRLDSGPSPASPLSSISAPNSTDATHLKFHPVFVPHSAP
FT AVLTNSNENRSNCVFEFHAQTPSSSGEGGGILPQRVYRNRQVAVDSNQEELSPQSVGLH
FT CHLQPVTEEQRNNHAPELTISVVEPMGQIWPIGSPEYSSDSSQITSSDLSDFQSPPPTG
FT GTAAPFGSDVSLPFIRLPQTVLQESPLFFCFPQGTTSQQVLSASYSSGGSTLHPQAQGQ
FT NQGQPSSSLAGVLSSQPIQHPQQQGIQPTVPSQQAVQYSLPQAASSSEGTTAQPVSQPQ
FT VSAGT (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_040272"
FT VAR_SEQ 784..1032
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040273"
FT VAR_SEQ 784..937
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040274"
FT VAR_SEQ 784..788
FT /note="LPVSQ -> VNSNF (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_040275"
FT VAR_SEQ 789..2377
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_040276"
FT VAR_SEQ 1787..1814
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040277"
FT MUTAGEN 368
FT /note="D->A: No effect on inhibition of SLC4A4."
FT /evidence="ECO:0000269|PubMed:21317537"
FT CONFLICT 1220
FT /note="G -> R (in Ref. 1; AAQ77243)"
FT /evidence="ECO:0000305"
FT CONFLICT 1230
FT /note="S -> C (in Ref. 1; AAQ77243)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2377 AA; 250934 MW; 0C4D288CCE50B8C6 CRC64;
MSDGAAEKQS GTPGFLTPPA PVPKNGSSSD SSVGEKLGAT VADSGVGRTE EYRRRRHTMD
KDSRGAAATT TPTEHRFFRR SVICDSNATA LELPGLPLSI PQPSVPAVVP QSAPPEPHRE
ETLTATVASQ VSQQPSAAAS PGEQAVVGSA TTTVPSSTSK DRPVSQPSLV GSKEEPPPSR
SGSGSGGASA KEAQEDRSQQ 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
QAGIQQLSAA STGIPTAPAT SASVSTQVEP EEPEADQHQQ LQYQQPSISV LSDGTIDSGQ
GSSVFTESRV SSQQTVSYGS QHEQAHSTGT APGHTVSSIQ AQSQPHGVYP PSSMAQGQNQ
GQPSSSLAGV LSSQPIQHPQ QQGIQPTVPS QQAVQYSLPQ AASSSEGTTA QPVSQPQVSA
GTQLPVSQTV ATVQGEPHIP VSTQPSVVPV HSGAHFLPMG QPIPTSLLPQ YPVSQIPIST
PHVSTAQTGF SSVPITMAAG INQPLLTLAS SATASSIPGG SPVVPNQLPT LLQPVNQLQS
QVHPQLLQPT TVQSIGIPAN LGQAAEGPLP SGDVLYQGFP SRLPPQYPGD SNIAPSSNVA
SVCIHSTVLA PPSMPTEALA TQGYFPTVVQ PYVESTPLVP MGSVGGQVQV SQPAVSLTQQ
PPTTSSQQAV LESTQGVSQA APPEQTPITQ SQPTQPVPLV TSADSAHSDV ASGMSDGNEN
APSSSGRHEG RTTKRHYRKS VRSRSRHEKT SRPKLRILNV SNKGDRVVEC QLETHNRKMV
TFKFDLDGDN PEEIATIMVN NDFILAIERE SFVAQVREII EKADEMLSED VSVEPEGDQG
LESLQGKDDY GFPGSQKLEG EFKQPIAVSS MPQQIGVPTS SLTQVVHSAG RRFIVSPVPE
SRLRESKVFT SDISDPVVAS TSQAPGMNLS HSASSLSLQQ AFSELKHGQM TEGPNTAPPN
FNHMAGPTFS PFLASIAGVQ TVAASTPSVS VPITSSPLND ISTSVMQSET ALPTEKGIVG
VTTTSTGVVA SGGLTTMSVS ESPTSSSAVS SSTVPAVVTV STPSQPVQAS TSGSIASSTG
SFPPGTFSTT TATTMGSVVA PDAKPPTVLL QQVASNTAGV AIVTSVSTTT PFPGMASQPS
LPLSSSTSAP TLAETMVVSA HSLDKASHSS TAGLGLSFCA PSSSSSSGTA VSTSVSQPGM
VHPLVISSAV VSTPGLPQPV VPTSTPLLPQ VPNIPPLVQP VVNVPAVQQT LIHSQPQPAL
LPNQPHTHCP EMDADTQSKA PGIDDIKTLE EKLRSLFSEH SSSGTQHASV SLETPLVVET
TVTPGITTTA VAPSKLMTST TSTCLPPTSL PLGAAGMPVM PVGTPGQVST PGTHASAPVG
TATGVKPGTT PPKPTKTVVP PVGTELSAGT VPCEQLPPFP GPSLIQSQQP LEDLDAQLRR
TLSPETITVA PAVGPLSTMS STTVTEAGTR LQKDGTEGHV TATSSGAGVV KMGRFQVSVT
MDDAQKERKN RSEDTKSVHF ESSTSESSVL SSSSPESTLV KPEPNGISIS GISLDVPDST
HKAPTPEAKS DAGQPTKVGR FQVTTTANKV GRFSVSRTED KVTELKKEGP VTSPPFRDSE
QTVIPAVIPK KEKPELAEPS HLNGPSSDLE AAFLSRGTED GSGSPHSPPH LCSKSLPVQN
LSQSLSNSFN SSYMSSDNES DIEDEDLRLE LRRLREKHLK EIQDLQSRQK HEIESLYTKL
GKVPPAVIIP PAAPLSGRRR RPTKSKGSKS SRSSSLGNKS PQLSGNLSGQ SGTSVLHPQQ
TLHPAGNTPE TGHNQLLQPL KPSPSSDNLY SAFTSDGAIS VPSLSAPGQG TSSTNTVGGT
VSSQAAQAQP PAMTSSRKGT FTDDLHKLVD NWARDAMNLS GRRGSKGHMN YEGPGMARKF
SAPGQLCVPM TSNLGGSTPI SAASATSLGH FTKSMCPPQQ YGFPPAPFGT QWSGTGGPAP
QPLGQFQPVG TASLQNFNIS NLQKSISNPP GSNLRTT
//
