S12A4_MOUSE
ID S12A4_MOUSE Reviewed; 1085 AA.
AC Q9JIS8; O55069; Q9ET57;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2002, sequence version 2.
DT 03-AUG-2022, entry version 156.
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=mKCC1;
GN Name=Slc12a4; Synonyms=Kcc1;
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].
RC STRAIN=DBA; 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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RC STRAIN=CD-1; TISSUE=Brain, and Spleen;
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 [3]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=11004507; DOI=10.1016/s0167-4781(00)00118-4;
RA Shmukler B.E., Brugnara C., Alper S.L.;
RT "Structure and genetic polymorphism of the mouse KCC1 gene.";
RL Biochim. Biophys. Acta 1492:353-361(2000).
RN [4]
RP 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 [5]
RP IDENTIFICATION BY 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-331.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-331.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24 AND SER-967, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC 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).
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.
CC -!- ACTIVITY REGULATION: Inhibited by WNK3. {ECO:0000250}.
CC -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC cotransporters. {ECO:0000269|PubMed:11551954}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected in embryo, adult heart, erythrocytes,
CC brain, kidney, stomach, ovary, testis and liver.
CC -!- DEVELOPMENTAL STAGE: Expression levels remained constant upon induction
CC of erythroid differentiation of embryonic stem cells. Not detected in
CC reticulocytes, but present during differentiation of erythroleukemia
CC cells to erythroblasts.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19349973,
CC ECO:0000269|PubMed:19656770}.
CC -!- MISCELLANEOUS: Activated by N-ethylmaleimide (NEM). Inhibited by DIOA.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; AF047339; AAC32816.1; -; mRNA.
DR EMBL; AF121118; AAF02444.1; -; mRNA.
DR EMBL; AF191023; AAF91094.1; -; Genomic_DNA.
DR EMBL; AH009673; AAF91090.1; -; Genomic_DNA.
DR CCDS; CCDS22623.1; -.
DR RefSeq; NP_033221.1; NM_009195.3.
DR AlphaFoldDB; Q9JIS8; -.
DR SMR; Q9JIS8; -.
DR BioGRID; 203279; 2.
DR IntAct; Q9JIS8; 5.
DR MINT; Q9JIS8; -.
DR STRING; 10090.ENSMUSP00000112130; -.
DR GlyGen; Q9JIS8; 4 sites.
DR iPTMnet; Q9JIS8; -.
DR PhosphoSitePlus; Q9JIS8; -.
DR EPD; Q9JIS8; -.
DR jPOST; Q9JIS8; -.
DR MaxQB; Q9JIS8; -.
DR PaxDb; Q9JIS8; -.
DR PRIDE; Q9JIS8; -.
DR ProteomicsDB; 256859; -.
DR Antibodypedia; 29685; 182 antibodies from 31 providers.
DR DNASU; 20498; -.
DR Ensembl; ENSMUST00000116429; ENSMUSP00000112130; ENSMUSG00000017765.
DR GeneID; 20498; -.
DR KEGG; mmu:20498; -.
DR UCSC; uc009ner.2; mouse.
DR CTD; 6560; -.
DR MGI; MGI:1309465; Slc12a4.
DR VEuPathDB; HostDB:ENSMUSG00000017765; -.
DR eggNOG; KOG2082; Eukaryota.
DR GeneTree; ENSGT00940000157672; -.
DR HOGENOM; CLU_001883_1_2_1; -.
DR InParanoid; Q9JIS8; -.
DR OMA; WTRDKHM; -.
DR PhylomeDB; Q9JIS8; -.
DR TreeFam; TF313657; -.
DR Reactome; R-MMU-426117; Cation-coupled Chloride cotransporters.
DR BioGRID-ORCS; 20498; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Slc12a4; mouse.
DR PRO; PR:Q9JIS8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9JIS8; protein.
DR Bgee; ENSMUSG00000017765; Expressed in choroid plexus of fourth ventricle and 206 other tissues.
DR ExpressionAtlas; Q9JIS8; baseline and differential.
DR Genevisible; Q9JIS8; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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: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 Chloride; Glycoprotein; Ion transport; Membrane; Phosphoprotein; Potassium;
KW Potassium transport; Reference proteome; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1085
FT /note="Solute carrier family 12 member 4"
FT /id="PRO_0000178031"
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..415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
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:21183079"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHW9"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UP95"
FT MOD_RES 967
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 983
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UP95"
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:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
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"
SQ SEQUENCE 1085 AA; 120624 MW; 9094931060972E03 CRC64;
MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAEREDSDGQ GNHRENSPFL CPLDASRGND
YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGGRR RAAKAPSMGT
LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV
PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGT
HDMSSATLNN MRVYGTIFLT LMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF
DPPVFPVCML GNRTLSRDQF DICAKTVVVD NETVATRLWT FFCHSPNLTA DSCDPYFLLN
NVTEIPGIPG AAAGVLQENL WSAYLEKGEV VEKHGLPSTD TLGLKESLSL YVVADIATSF
TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAIV TTSLVYFSSV ILFGACIEGV
VLRDKYGDGV SRNLVVGTLA WPSPWVIVVG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP
FLRVFGHGKA NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT
LLRTPNWRPR FKYYHWTLSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE
WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA
GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMDIEKVKG FCQVVVASKV REGLAHLIQS
CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER
YLDGHIDVWW IVHDGGMLML LPFLLRQHKV WKKCRMRIFT VAQMDDNSIQ MKKDLAIFLY
HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTERDREA QLVKDRHSAL
RLESLYSDEE EESVAGADKI QMTWTRDKYM AEPWDPSHAP DNFRELVHIK PDQSNVRRMH
TAVKLNEVIV TRSHDARLVL LNMPGPPKNS EGDENYMEFL EVLTEGLERV LLVRGGGREV
ITIYS
