WNK4_MOUSE
ID WNK4_MOUSE Reviewed; 1222 AA.
AC Q80UE6; A2A4J7; Q4VAC1; Q80XB5; Q80XN2; Q8R0N0; Q8R340;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Serine/threonine-protein kinase WNK4 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9H4A3};
DE AltName: Full=Protein kinase lysine-deficient 4 {ECO:0000312|MGI:MGI:1917097};
DE AltName: Full=Protein kinase with no lysine 4 {ECO:0000303|PubMed:12515852};
GN Name=Wnk4 {ECO:0000312|MGI:MGI:1917097};
GN Synonyms=Prkwnk4 {ECO:0000312|MGI:MGI:1917097};
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 {ECO:0000312|EMBL:AAO21955.1};
RN [1] {ECO:0000312|EMBL:AAO21955.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAO21955.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAO21955.1};
RX PubMed=12515852; DOI=10.1073/pnas.242735399;
RA Wilson F.H., Kahle K.T., Sabath E., Lalioti M.D., Rapson A.K., Hoover R.S.,
RA Hebert S.C., Gamba G., Lifton R.P.;
RT "Molecular pathogenesis of inherited hypertension with hyperkalemia: The
RT Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:680-684(2003).
RN [2] {ECO:0000250|UniProtKB:Q9H4A3}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF GLU-559; ASP-561
RP AND GLN-562.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAO25619.1};
RX PubMed=12671053; DOI=10.1172/jci200317443;
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 [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].
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH43677.1};
RC TISSUE=Kidney {ECO:0000269|PubMed:15489334}, and Mammary carcinoma;
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] {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 [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH KCNJ1, AND MUTAGENESIS OF ASP-318.
RX PubMed=14608358; DOI=10.1038/ng1271;
RA Kahle K.T., Wilson F.H., Leng Q., Lalioti M.D., O'Connell A.D., Dong K.,
RA Rapson A.K., MacGregor G.G., Giebisch G., Hebert S.C., Lifton R.P.;
RT "WNK4 regulates the balance between renal NaCl reabsorption and K+
RT secretion.";
RL Nat. Genet. 35:372-376(2003).
RN [7]
RP FUNCTION, INTERACTION WITH WNK1 AND WNK3, AND PHOSPHORYLATION BY WNK1 AND
RP WNK3.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1196, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [9]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-318.
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 [10]
RP MUTAGENESIS OF ASP-561.
RX PubMed=23453970; DOI=10.1016/j.celrep.2013.02.024;
RA Wakabayashi M., Mori T., Isobe K., Sohara E., Susa K., Araki Y., Chiga M.,
RA Kikuchi E., Nomura N., Mori Y., Matsuo H., Murata T., Nomura S., Asano T.,
RA Kawaguchi H., Nonoyama S., Rai T., Sasaki S., Uchida S.;
RT "Impaired KLHL3-mediated ubiquitination of WNK4 causes human
RT hypertension.";
RL Cell Rep. 3:858-868(2013).
RN [11]
RP MUTAGENESIS OF GLN-562.
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).
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, SGK1, TRPV5 and TRPV6.
CC Regulates the activity of the thiazide-sensitive Na-Cl cotransporter,
CC SLC12A3, by phosphorylation which appears to prevent membrane
CC trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1,
CC via a kinase-independent mechanism by which it induces clearance of the
CC protein from the cell surface by clathrin-dependent endocytosis. WNK4
CC appears to act as a molecular switch that can vary the balance between
CC NaCl reabsorption and K(+) secretion to maintain integrated
CC homeostasis. Phosphorylates NEDD4L. Acts as a scaffold to inhibit
CC SLC4A4 as well as CFTR activities and surface expression, recruits
CC STK39 which mediates the inhibition (PubMed:21317537).
CC {ECO:0000269|PubMed:12671053, ECO:0000269|PubMed:14608358,
CC ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:21317537}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9H4A3};
CC -!- ACTIVITY REGULATION: Activation requires autophosphorylation of Ser-
CC 332. Phosphorylation of Ser-328 also promotes increased activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9JIH7}.
CC -!- SUBUNIT: Interacts with the C-terminal region of KCNJ1
CC (PubMed:14608358). Interacts with WNK1 and WNK3 (PubMed:17975670).
CC Interacts with KLHL3 (By similarity). {ECO:0000250|UniProtKB:Q96J92,
CC ECO:0000269|PubMed:14608358, ECO:0000269|PubMed:17975670}.
CC -!- INTERACTION:
CC Q80UE6; P69744: Trpv5; NbExp=2; IntAct=EBI-295378, EBI-538447;
CC Q80UE6; O00141: SGK1; Xeno; NbExp=2; IntAct=EBI-295378, EBI-1042854;
CC Q80UE6; Q13507-3: TRPC3; Xeno; NbExp=2; IntAct=EBI-295378, EBI-15563545;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000269|PubMed:11498583}. Note=Present exclusively in
CC intercellular junctions in the distal convoluted tubule and in both the
CC cytoplasm and intercellular junctions in the cortical collecting duct.
CC WNK4 is part of the tight junction complex.
CC {ECO:0000269|PubMed:11498583}.
CC -!- TISSUE SPECIFICITY: Locates to the distal convoluted tubule, the
CC medullary collecting duct and the cortical collecting duct of the
CC kidney (PubMed:11498583). Expressed in pancreatic duct
CC (PubMed:21317537). {ECO:0000269|PubMed:11498583,
CC ECO:0000269|PubMed:21317537}.
CC -!- PTM: Phosphorylated by WNK1 and WNK3. {ECO:0000269|PubMed:17975670}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL3) complex, leading to its
CC degradation and increased expression of KCNJ1 at the cell surface.
CC Ubiquitinated by the BCR(KLHL2) complex (By similarity).
CC {ECO:0000250|UniProtKB:Q96J92}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. WNK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- CAUTION: Was named WNK/'with no lysine(K)' because key residues for
CC catalysis, including the lysine involved in ATP binding, are either not
CC conserved or differ compared to the residues described in other kinase
CC family proteins. {ECO:0000250|UniProtKB:Q9H4A3}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26679.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH43677.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO25619.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY187027; AAO21955.1; -; mRNA.
DR EMBL; AY184228; AAO25619.1; ALT_INIT; mRNA.
DR EMBL; AL590969; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026591; AAH26591.1; -; mRNA.
DR EMBL; BC026679; AAH26679.1; ALT_INIT; mRNA.
DR EMBL; BC043677; AAH43677.1; ALT_INIT; mRNA.
DR EMBL; BC096453; AAH96453.1; -; mRNA.
DR CCDS; CCDS25459.1; -.
DR RefSeq; NP_783569.1; NM_175638.3.
DR AlphaFoldDB; Q80UE6; -.
DR SMR; Q80UE6; -.
DR BioGRID; 213713; 6.
DR DIP; DIP-33231N; -.
DR ELM; Q80UE6; -.
DR IntAct; Q80UE6; 6.
DR MINT; Q80UE6; -.
DR STRING; 10090.ENSMUSP00000099397; -.
DR iPTMnet; Q80UE6; -.
DR PhosphoSitePlus; Q80UE6; -.
DR MaxQB; Q80UE6; -.
DR PaxDb; Q80UE6; -.
DR PRIDE; Q80UE6; -.
DR ProteomicsDB; 299696; -.
DR Antibodypedia; 29411; 243 antibodies from 26 providers.
DR DNASU; 69847; -.
DR Ensembl; ENSMUST00000103108; ENSMUSP00000099397; ENSMUSG00000035112.
DR GeneID; 69847; -.
DR KEGG; mmu:69847; -.
DR UCSC; uc007loe.2; mouse.
DR CTD; 65266; -.
DR MGI; MGI:1917097; Wnk4.
DR VEuPathDB; HostDB:ENSMUSG00000035112; -.
DR eggNOG; KOG0584; Eukaryota.
DR GeneTree; ENSGT00940000159871; -.
DR HOGENOM; CLU_000550_2_1_1; -.
DR InParanoid; Q80UE6; -.
DR OMA; AMVHNEF; -.
DR OrthoDB; 27514at2759; -.
DR PhylomeDB; Q80UE6; -.
DR TreeFam; TF315363; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 69847; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Wnk4; mouse.
DR PRO; PR:Q80UE6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q80UE6; protein.
DR Bgee; ENSMUSG00000035112; Expressed in humerus cartilage element and 188 other tissues.
DR ExpressionAtlas; Q80UE6; baseline and differential.
DR Genevisible; Q80UE6; MM.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; IMP:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; ISO:MGI.
DR GO; GO:0031404; F:chloride ion binding; IMP:MGI.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:MGI.
DR GO; GO:0035932; P:aldosterone secretion; IMP:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; IMP:MGI.
DR GO; GO:0030003; P:cellular cation homeostasis; IDA:GO_Central.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; IMP:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IMP:MGI.
DR GO; GO:0006821; P:chloride transport; IDA:MGI.
DR GO; GO:0072156; P:distal tubule morphogenesis; ISS:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0050801; P:ion homeostasis; IMP:MGI.
DR GO; GO:0006811; P:ion transport; IDA:UniProtKB.
DR GO; GO:0042116; P:macrophage activation; IMP:MGI.
DR GO; GO:0090188; P:negative regulation of pancreatic juice secretion; IMP:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; ISS:UniProtKB.
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:0071805; P:potassium ion transmembrane transport; IMP:MGI.
DR GO; GO:0070528; P:protein kinase C signaling; IDA:MGI.
DR GO; GO:0008104; P:protein localization; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0045859; P:regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0070294; P:renal sodium ion absorption; ISS:UniProtKB.
DR GO; GO:0002021; P:response to dietary excess; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IGI:MGI.
DR GO; GO:0007165; P:signal transduction; IMP:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:MGI.
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 ATP-binding; Cell junction; Isopeptide bond; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Tight junction; Transferase; Ubl conjugation.
FT CHAIN 1..1222
FT /note="Serine/threonine-protein kinase WNK4"
FT /id="PRO_0000086825"
FT DOMAIN 171..429
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 525..562
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..659
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 747..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 877..896
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 927..976
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1000..1087
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1166..1222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..60
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..99
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..160
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 531..555
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 779..800
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 931..945
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 949..971
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1000..1039
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1047..1073
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1168..1183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1194..1211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 318
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT BINDING 181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 251..254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT BINDING 301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H4A3"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT MOD_RES 328
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 332
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9JIH7"
FT MOD_RES 1014
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TPK6"
FT MOD_RES 1196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 154
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 172
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 183
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 223
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 238
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 325
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 384
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 390
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 447
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 451
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 990
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 1123
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 1136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT CROSSLNK 1137
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q96J92"
FT MUTAGEN 318
FT /note="D->A: No effect on inhibition of KCNJ1."
FT /evidence="ECO:0000269|PubMed:14608358"
FT MUTAGEN 318
FT /note="D->E: No effect on inhibition of SLC4A4."
FT /evidence="ECO:0000269|PubMed:21317537"
FT MUTAGEN 559
FT /note="E->K: No effect on inhibition of SLC12A3."
FT /evidence="ECO:0000269|PubMed:12671053"
FT MUTAGEN 561
FT /note="D->A: Increased protein level, probably due to
FT defects in ubiquitination. No effect on inhibition of
FT SLC12A3."
FT /evidence="ECO:0000269|PubMed:12671053,
FT ECO:0000269|PubMed:23453970"
FT MUTAGEN 562
FT /note="Q->E: Increased protein level, probably due to
FT defects in ubiquitination. Prevents inhibition of SLC12A3."
FT /evidence="ECO:0000269|PubMed:12671053,
FT ECO:0000269|PubMed:23576762"
FT CONFLICT 179
FT /note="R -> K (in Ref. 2; AAO25619)"
FT /evidence="ECO:0000305"
FT CONFLICT 607
FT /note="S -> F (in Ref. 4; AAH26679)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1222 AA; 132410 MW; BE0A193E7D79DCFE CRC64;
MLAPRNTETG VPMSQTEADL ALRPSPALTS TGPTRLGPPP RRVRRFSGKA EPRPRSSRPS
RRSSVDLGLL SSWSQPASLL PEPPDPPDSA GPTRSPPSSS KEPPEGTWMG AAPVKAVDSA
CPELTGSSGG PGSREPPRVP DAAARERRRE QEEKEDTETQ AVATSPDGRY LKFDIEIGRG
SFKTVYRGLD TDTTVEVAWC ELQTRKLSRA ERQRFSEEVE MLKGLQHPNI VRFYDSWKSV
LRGQVCIVLV TELMTSGTLK TYLRRFREMK PRVLQRWSRQ ILRGLHFLHS RVPPILHRDL
KCDNVFITGP SGSVKIGDLG LATLKRASFA KSVIGTPEFM APEMYEEKYD EAVDVYAFGM
CMLEMATSEY PYSECQNAAQ IYRKVTSGTK PNSFYKVKMP EVKEIIEGCI RTDKNERFTI
QDLLAHAFFR EERGVHVELA EEDDGEKPGL KLWLRMEDAR RGGRPRDNQA IEFLFQLGRD
AAEEVAQEMV ALGLVCEADY QPVARAVRER VAAIQRKREK LRKARELEVL PPDSGPPPAT
VSLAPGPPSA FPPEPEEPEA DQHQSFLFRH ASYSSTTSDC ETDGYLSSSG FLDASDPALQ
PPGGLPSSPA ESHLCLPSGF ALSIPRSGPG SDFSPGDSYA SDAASGLSDM GEGGQMRKNP
VKTLRRRPRS RLRVTSVSDQ SDRVVECQLQ THNSKMVTFR FDLDGDSPEE IAAAMVYNEF
ILPSERDGFL SRIREIIQRV ETLLKRDAGP PEAAEDALSP QEEPAALPAL PGPPNAEPQR
SISPEQRSWA AFSTSPSSPG TPLSPGAPFS PGTPPVFPCP IFPITSPSCY PCPFSQVSSN
PYPQAPSSLL PLSSSASQVP LPSSSLPISA PLPFSPSYPQ DPLSPTSLPV CPSPPSLPST
TAAPLLSLAS AFSLAVMTVA QSLLSPSPGL LSQSPPAPPG PLPSLPLSLA SCDQESLSAQ
TAETENEASR NPAQPLLGDA RLAPISEEGK PQLVGRFQVT SSKEPAEPPL QPASPTLSRS
LKLPSPPLTS ESSDTEDSAA GGPETREALA ESDRAAEGLG VAVDDEKDEG KEPLLGGSSP
ILSHPSPVWM NYSYSSLCLS SEESESSGED EEFWAELQNL RQKHLSEVEA LQTLQKKEIE
DLYSRLGKQP PPGIVAPAAM LSCRQRRLSK GSFPTSRRNS LQRSDLPGPG IMRRNSLSGS
STGSQEQRAS KGVTFAGDIG RM
