S12A4_RAT
ID S12A4_RAT Reviewed; 1085 AA.
AC Q63632; P70632;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 154.
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=rKCC1;
DE AltName: Full=Furosemide-sensitive K-Cl cotransporter;
GN Name=Slc12a4; Synonyms=Kcc1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
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] OF 842-970.
RC STRAIN=Wistar Kyoto; TISSUE=Aorta;
RA Adams L.A., Werny I., Schwartz S.M.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP GLYCOSYLATION.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Inhibited by WNK3. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10564083}.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U55815; AAC52634.1; -; mRNA.
DR EMBL; U75396; AAB18960.1; -; mRNA.
DR PIR; T31429; T31429.
DR RefSeq; NP_062102.1; NM_019229.2.
DR AlphaFoldDB; Q63632; -.
DR SMR; Q63632; -.
DR STRING; 10116.ENSRNOP00000026730; -.
DR TCDB; 2.A.30.1.13; the cation-chloride cotransporter (ccc) family.
DR GlyGen; Q63632; 4 sites.
DR iPTMnet; Q63632; -.
DR PhosphoSitePlus; Q63632; -.
DR PaxDb; Q63632; -.
DR PRIDE; Q63632; -.
DR Ensembl; ENSRNOT00000026730; ENSRNOP00000026730; ENSRNOG00000019651.
DR GeneID; 29501; -.
DR KEGG; rno:29501; -.
DR UCSC; RGD:3687; rat.
DR CTD; 6560; -.
DR RGD; 3687; Slc12a4.
DR eggNOG; KOG2082; Eukaryota.
DR GeneTree; ENSGT00940000157672; -.
DR HOGENOM; CLU_001883_1_2_1; -.
DR InParanoid; Q63632; -.
DR OMA; WTRDKHM; -.
DR OrthoDB; 349744at2759; -.
DR PhylomeDB; Q63632; -.
DR Reactome; R-RNO-426117; Cation-coupled Chloride cotransporters.
DR PRO; PR:Q63632; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000019651; Expressed in ovary and 18 other tissues.
DR Genevisible; Q63632; RN.
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:RGD.
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_0000178033"
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 REGION 32..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UP95"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIS8"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UP95"
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:22673903"
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: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 CONFLICT 940
FT /note="R -> K (in Ref. 2; AAB18960)"
FT /evidence="ECO:0000305"
FT CONFLICT 949
FT /note="E -> K (in Ref. 2; AAB18960)"
FT /evidence="ECO:0000305"
FT CONFLICT 959
FT /note="A -> G (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 961
FT /note="R -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 963..964
FT /note="ES -> KN (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 969
FT /note="E -> K (in Ref. 2; AAB18960)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1085 AA; 120628 MW; 1C90B7C3F15857F9 CRC64;
MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAEREDSDGQ GNHRENSPFL SPLDASRGND
YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGGRR RAAKAPSMGT
LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV
PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGT
HDMSSATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYVGGIKSAF
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 FKYYHWALSF LGMSLCLALM FVSSWYYALV AMVIAGMIYK YIEYQGAEKE
WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA
GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS
CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER
YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WKKCRMRIFT VAQMDDNSIQ MKKDLAIFLY
HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTERDREA QLVKDRHSAL
RLESLYSDEE DESVTGADKI QMTWTRDKYM AEPWDPSHAP DNFRELVHIK PDQSNVRRMH
TAVKLNEVIV TRSHDARLVL LNMPGPPKNS EGDENYMEFL EVLTEGLERV LLVRGGGREV
ITIYS
