S12A4_HUMAN
ID S12A4_HUMAN Reviewed; 1085 AA.
AC Q9UP95; B4DF69; B4DR04; B4DZ82; B7ZAV0; F5H066; F5H0S9; F5H3C0; O60632;
AC O75893; Q13953; Q96LD5;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2002, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Solute carrier family 12 member 4;
DE AltName: Full=Electroneutral potassium-chloride cotransporter 1;
DE AltName: Full=Erythroid K-Cl cotransporter 1;
DE Short=hKCC1;
GN Name=SLC12A4; Synonyms=KCC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Embryonic kidney;
RX PubMed=8663127; DOI=10.1074/jbc.271.27.16237;
RA Gillen C.M., Brill S., Payne J.A., Forbush B. III;
RT "Molecular cloning and functional expression of the K-Cl cotransporter from
RT rabbit, rat, and human. A new member of the cation-chloride cotransporter
RT family.";
RL J. Biol. Chem. 271:16237-16244(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Erythroleukemia;
RX PubMed=9516379; DOI=10.1006/bcmd.1998.0168;
RA Pellegrino C.M., Rybicki A.C., Musto S., Nagel R.L., Schwartz R.S.;
RT "Molecular identification and expression of erythroid K:Cl cotransporter in
RT human and mouse erythroleukemic cells.";
RL Blood Cells Mol. Dis. 24:31-40(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 25-1087 (ISOFORM 7).
RC TISSUE=Cerebellum, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 280-517.
RC TISSUE=Erythroleukemia;
RA Golding S., Culliford S.J., Ellory J.C.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 684-1085 (ISOFORM 4), AND SUBUNIT.
RX PubMed=11551954; DOI=10.1074/jbc.m107155200;
RA Casula S., Shmukler B.E., Wilhelm S., Stuart-Tilley A.K., Su W.,
RA Chernova M.N., Brugnara C., Alper S.L.;
RT "A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-
RT terminal cytoplasmic domains are required for K-Cl cotransport activity.";
RL J. Biol. Chem. 276:41870-41878(2001).
RN [8]
RP EXPRESSION IN ERYTHROCYTE MEMBRANES.
RX PubMed=10564083; DOI=10.1152/ajpcell.1999.277.5.c899;
RA Su W., Shmukler B.E., Chernova M.N., Stuart-Tilley A.K., de Franceschi L.,
RA Brugnara C., Alper S.L.;
RT "Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression,
RT and functional regulation.";
RL Am. J. Physiol. 277:C899-C912(1999).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51 AND SER-967, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP ACTIVITY REGULATION.
RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011;
RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A.,
RA Pasantes-Morales H., Gamba G., Mercado A.;
RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.";
RL Am. J. Physiol. 301:C601-C608(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-51; SER-88; SER-967
RP AND THR-983, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport when
CC activated by cell swelling. May contribute to cell volume homeostasis
CC in single cells. May be involved in the regulation of basolateral Cl(-)
CC exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no
CC transport activity. {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Inhibited by WNK3. {ECO:0000269|PubMed:21613606}.
CC -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC cotransporters. {ECO:0000269|PubMed:11551954}.
CC -!- INTERACTION:
CC Q9UP95; Q9Y2T2: AP3M1; NbExp=3; IntAct=EBI-7244836, EBI-2371151;
CC Q9UP95; Q9BYD5: CNFN; NbExp=3; IntAct=EBI-7244836, EBI-12819063;
CC Q9UP95; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7244836, EBI-3867333;
CC Q9UP95; P59991: KRTAP12-2; NbExp=3; IntAct=EBI-7244836, EBI-10176379;
CC Q9UP95; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-7244836, EBI-12196745;
CC Q9UP95; Q8IYB1: MB21D2; NbExp=3; IntAct=EBI-7244836, EBI-11323212;
CC Q9UP95; Q8N9M5: TMEM102; NbExp=3; IntAct=EBI-7244836, EBI-1050459;
CC Q9UP95; Q8N720: ZNF655; NbExp=3; IntAct=EBI-7244836, EBI-625509;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9UP95-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UP95-2; Sequence=VSP_006113, VSP_006114;
CC Name=3;
CC IsoId=Q9UP95-3; Sequence=VSP_006112;
CC Name=4;
CC IsoId=Q9UP95-4; Sequence=VSP_006108, VSP_006109, VSP_006110,
CC VSP_006111;
CC Name=5;
CC IsoId=Q9UP95-5; Sequence=VSP_044596;
CC Name=6;
CC IsoId=Q9UP95-6; Sequence=VSP_046146;
CC Name=7;
CC IsoId=Q9UP95-7; Sequence=VSP_046369;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Levels are much higher in erythrocytes
CC from patients with Hb SC and Hb SS compared to normal AA erythrocytes.
CC This may contribute to red blood cell dehydration and to the
CC manifestation of sickle cell disease by increasing the intracellular
CC concentration of HbS. Isoform 1 was not detected in circulating
CC reticulocytes.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC35282.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAG57330.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U55054; AAC50563.1; -; mRNA.
DR EMBL; AF047338; AAC32815.1; -; mRNA.
DR EMBL; AF054505; AAC39684.1; -; mRNA.
DR EMBL; AF054506; AAC39685.1; -; mRNA.
DR EMBL; AK293956; BAG57330.1; ALT_INIT; mRNA.
DR EMBL; AK299042; BAG61116.1; -; mRNA.
DR EMBL; AK302790; BAG63994.1; -; mRNA.
DR EMBL; AK316415; BAH14786.1; -; mRNA.
DR EMBL; AC040162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021193; AAH21193.1; -; mRNA.
DR EMBL; AF053402; AAC35282.1; ALT_FRAME; mRNA.
DR EMBL; AY026038; AAK01946.1; -; mRNA.
DR CCDS; CCDS10855.1; -. [Q9UP95-1]
DR CCDS; CCDS54030.1; -. [Q9UP95-6]
DR CCDS; CCDS54031.1; -. [Q9UP95-5]
DR CCDS; CCDS54032.1; -. [Q9UP95-7]
DR RefSeq; NP_001139433.1; NM_001145961.1.
DR RefSeq; NP_001139434.1; NM_001145962.1. [Q9UP95-7]
DR RefSeq; NP_001139435.1; NM_001145963.1. [Q9UP95-6]
DR RefSeq; NP_001139436.1; NM_001145964.1. [Q9UP95-5]
DR RefSeq; NP_005063.1; NM_005072.4. [Q9UP95-1]
DR PDB; 6KKR; EM; 2.90 A; A/B=1-1085.
DR PDB; 6KKT; EM; 2.90 A; A/B=1-1085.
DR PDB; 6KKU; EM; 3.50 A; A/B=1-1085.
DR PDB; 7AIP; EM; 3.12 A; A/B=20-1085.
DR PDB; 7AIQ; EM; 3.72 A; A/B=20-1085.
DR PDB; 7AIR; EM; 3.66 A; A/B=20-1085.
DR PDBsum; 6KKR; -.
DR PDBsum; 6KKT; -.
DR PDBsum; 6KKU; -.
DR PDBsum; 7AIP; -.
DR PDBsum; 7AIQ; -.
DR PDBsum; 7AIR; -.
DR AlphaFoldDB; Q9UP95; -.
DR SMR; Q9UP95; -.
DR BioGRID; 112449; 139.
DR IntAct; Q9UP95; 38.
DR MINT; Q9UP95; -.
DR STRING; 9606.ENSP00000395983; -.
DR DrugBank; DB00887; Bumetanide.
DR DrugBank; DB00761; Potassium chloride.
DR TCDB; 2.A.30.1.17; the cation-chloride cotransporter (ccc) family.
DR GlyGen; Q9UP95; 5 sites.
DR iPTMnet; Q9UP95; -.
DR PhosphoSitePlus; Q9UP95; -.
DR BioMuta; SLC12A4; -.
DR DMDM; 27151691; -.
DR EPD; Q9UP95; -.
DR jPOST; Q9UP95; -.
DR MassIVE; Q9UP95; -.
DR MaxQB; Q9UP95; -.
DR PaxDb; Q9UP95; -.
DR PeptideAtlas; Q9UP95; -.
DR PRIDE; Q9UP95; -.
DR ProteomicsDB; 25245; -.
DR ProteomicsDB; 25434; -.
DR ProteomicsDB; 26226; -.
DR ProteomicsDB; 85360; -. [Q9UP95-1]
DR ProteomicsDB; 85361; -. [Q9UP95-2]
DR ProteomicsDB; 85362; -. [Q9UP95-3]
DR ProteomicsDB; 85363; -. [Q9UP95-4]
DR Antibodypedia; 29685; 182 antibodies from 31 providers.
DR DNASU; 6560; -.
DR Ensembl; ENST00000316341.8; ENSP00000318557.3; ENSG00000124067.17. [Q9UP95-1]
DR Ensembl; ENST00000422611.6; ENSP00000395983.2; ENSG00000124067.17. [Q9UP95-7]
DR Ensembl; ENST00000537830.6; ENSP00000445962.2; ENSG00000124067.17. [Q9UP95-6]
DR Ensembl; ENST00000541864.6; ENSP00000438334.2; ENSG00000124067.17. [Q9UP95-5]
DR Ensembl; ENST00000576616.5; ENSP00000458902.1; ENSG00000124067.17. [Q9UP95-2]
DR GeneID; 6560; -.
DR KEGG; hsa:6560; -.
DR MANE-Select; ENST00000316341.8; ENSP00000318557.3; NM_005072.5; NP_005063.1.
DR UCSC; uc002euz.2; human. [Q9UP95-1]
DR CTD; 6560; -.
DR DisGeNET; 6560; -.
DR GeneCards; SLC12A4; -.
DR HGNC; HGNC:10913; SLC12A4.
DR HPA; ENSG00000124067; Low tissue specificity.
DR MalaCards; SLC12A4; -.
DR MIM; 604119; gene.
DR neXtProt; NX_Q9UP95; -.
DR OpenTargets; ENSG00000124067; -.
DR PharmGKB; PA35807; -.
DR VEuPathDB; HostDB:ENSG00000124067; -.
DR eggNOG; KOG2082; Eukaryota.
DR GeneTree; ENSGT00940000157672; -.
DR HOGENOM; CLU_001883_1_1_1; -.
DR InParanoid; Q9UP95; -.
DR OMA; WTRDKHM; -.
DR OrthoDB; 349744at2759; -.
DR PhylomeDB; Q9UP95; -.
DR TreeFam; TF313657; -.
DR PathwayCommons; Q9UP95; -.
DR Reactome; R-HSA-426117; Cation-coupled Chloride cotransporters.
DR SignaLink; Q9UP95; -.
DR SIGNOR; Q9UP95; -.
DR BioGRID-ORCS; 6560; 25 hits in 1083 CRISPR screens.
DR ChiTaRS; SLC12A4; human.
DR GeneWiki; Chloride_potassium_symporter_4; -.
DR GenomeRNAi; 6560; -.
DR Pharos; Q9UP95; Tbio.
DR PRO; PR:Q9UP95; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9UP95; protein.
DR Bgee; ENSG00000124067; Expressed in apex of heart and 143 other tissues.
DR ExpressionAtlas; Q9UP95; baseline and differential.
DR Genevisible; Q9UP95; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0008519; F:ammonium transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0140157; P:ammonium import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0006884; P:cell volume homeostasis; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0055064; P:chloride ion homeostasis; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0055075; P:potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR000622; KCC1.
DR InterPro; IPR000076; KCL_cotranspt.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR PANTHER; PTHR11827:SF46; PTHR11827:SF46; 1.
DR Pfam; PF00324; AA_permease; 2.
DR Pfam; PF03522; SLC12; 2.
DR PRINTS; PR01081; KCLTRNSPORT.
DR PRINTS; PR01082; KCLTRNSPORT1.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chloride; Glycoprotein; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium transport;
KW Reference proteome; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1085
FT /note="Solute carrier family 12 member 4"
FT /id="PRO_0000178030"
FT TOPO_DOM 1..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..214
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..407
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 408..428
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 453..473
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..493
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 588..627
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 628..648
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 845..865
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 866..1085
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIS8"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHW9"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 983
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..70
FT /note="MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSDGHGNHRESSPFLSP
FT LEASRGIDYYDRNLALFE -> MRAGGACRPGAAGTAAGTAAGGWDGGCGGAEPARCLT
FT SPWCQWTGRGAATMTTSRGSVGWTTGSAPSWMTRT (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046369"
FT VAR_SEQ 1..38
FT /note="MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSD -> MGDTLSP
FT (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044596"
FT VAR_SEQ 1..38
FT /note="MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSD -> MAAEGAVCGF
FT VYLEGTAWAVPEDTEPLASCTL (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046146"
FT VAR_SEQ 749..955
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11551954"
FT /id="VSP_006108"
FT VAR_SEQ 956..958
FT /note="RHS -> PCA (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11551954"
FT /id="VSP_006109"
FT VAR_SEQ 963..987
FT /note="ESLYSDEEDESAVGADKIQMTWTRD -> PTWPCSCPRTSPSTPATTSATWR
FT AT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11551954"
FT /id="VSP_006110"
FT VAR_SEQ 988..1085
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11551954"
FT /id="VSP_006111"
FT VAR_SEQ 1012..1085
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9516379"
FT /id="VSP_006112"
FT VAR_SEQ 1056..1068
FT /note="YMEFLEVLTEGLE -> CIPLWRGRQLGGG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9516379"
FT /id="VSP_006113"
FT VAR_SEQ 1069..1085
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9516379"
FT /id="VSP_006114"
FT CONFLICT 42
FT /note="N -> D (in Ref. 3; BAG61116)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="F -> L (in Ref. 3; BAG63994)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="I -> N (in Ref. 3; BAG63994)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="G -> R (in Ref. 3; BAG57330)"
FT /evidence="ECO:0000305"
FT CONFLICT 697
FT /note="L -> P (in Ref. 3; BAG63994)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="V -> A (in Ref. 3; BAG57330)"
FT /evidence="ECO:0000305"
FT CONFLICT 1055
FT /note="N -> D (in Ref. 3; BAG57330)"
FT /evidence="ECO:0000305"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 125..132
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 136..139
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 141..175
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 186..193
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 195..226
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 245..268
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 270..275
FT /evidence="ECO:0007829|PDB:6KKR"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 279..300
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:7AIP"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 325..329
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 332..335
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 337..343
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 355..359
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 362..367
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 373..378
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 408..410
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 420..427
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:6KKR"
FT TURN 439..443
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 447..476
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 479..482
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:6KKR"
FT TURN 488..492
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 505..535
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 540..546
FT /evidence="ECO:0007829|PDB:6KKR"
FT STRAND 550..552
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 556..569
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 574..601
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 616..633
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 635..651
FT /evidence="ECO:0007829|PDB:6KKR"
FT HELIX 665..681
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 694..697
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 710..719
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 725..733
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 735..737
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 740..755
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 761..769
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 770..779
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 790..792
FT /evidence="ECO:0007829|PDB:7AIP"
FT TURN 797..801
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 806..819
FT /evidence="ECO:0007829|PDB:7AIP"
FT TURN 820..822
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 824..830
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 831..833
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 845..848
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 855..866
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 869..871
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 875..880
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 888..902
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 907..910
FT /evidence="ECO:0007829|PDB:7AIP"
FT TURN 915..918
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 919..925
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 1015..1032
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 1039..1042
FT /evidence="ECO:0007829|PDB:7AIP"
FT TURN 1050..1052
FT /evidence="ECO:0007829|PDB:7AIP"
FT HELIX 1053..1063
FT /evidence="ECO:0007829|PDB:7AIP"
FT STRAND 1068..1074
FT /evidence="ECO:0007829|PDB:7AIP"
FT CONFLICT Q9UP95-6:4
FT /note="E -> G (in Ref. 3; BAH14786)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1085 AA; 120650 MW; 42B590EC3D94EA4D CRC64;
MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID
YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT
LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV
PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA
HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF
DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN
NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF
TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV
VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP
FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT
LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE
WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA
GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS
CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER
YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQMDDNSIQ MKKDLAVFLY
HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTEREREA QLVKDRHSAL
RLESLYSDEE DESAVGADKI QMTWTRDKYM TETWDPSHAP DNFRELVHIK PDQSNVRRMH
TAVKLNEVIV TRSHDARLVL LNMPGPPRNS EGDENYMEFL EVLTEGLERV LLVRGGGREV
ITIYS
