S12A1_RAT
ID S12A1_RAT Reviewed; 1095 AA.
AC P55016;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Solute carrier family 12 member 1;
DE AltName: Full=Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1 {ECO:0000303|PubMed:8021284};
DE Short=BSC1;
DE AltName: Full=Kidney-specific Na-K-Cl symporter;
GN Name=Slc12a1; Synonyms=Nkcc2;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8021284; DOI=10.1016/s0021-9258(17)32499-7;
RA Gamba G., Miyanoshita A., Lombardi M., Lytton J., Lee W.S., Hediger M.A.,
RA Hebert S.C.;
RT "Molecular cloning, primary structure, and characterization of two members
RT of the mammalian electroneutral sodium-(potassium)-chloride cotransporter
RT family expressed in kidney.";
RL J. Biol. Chem. 269:17713-17722(1994).
RN [2]
RP PHOSPHORYLATION AT SER-126.
RX PubMed=17341212; DOI=10.1042/bj20061850;
RA Fraser S.A., Gimenez I., Cook N., Jennings I., Katerelos M., Katsis F.,
RA Levidiotis V., Kemp B.E., Power D.A.;
RT "Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-
RT activated protein kinase (AMPK).";
RL Biochem. J. 405:85-93(2007).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-114; SER-116 AND SER-144, AND
RP IDENTIFICATION BY 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).
RN [4]
RP INTERACTION WITH PPP3CB, TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-96;
RP THR-101 AND THR-114.
RX PubMed=25967121; DOI=10.1681/asn.2014070728;
RA Borschewski A., Himmerkus N., Boldt C., Blankenstein K.I., McCormick J.A.,
RA Lazelle R., Willnow T.E., Jankowski V., Plain A., Bleich M., Ellison D.H.,
RA Bachmann S., Mutig K.;
RT "Calcineurin and sorting-related receptor with A-type repeats interact to
RT regulate the renal Na(+)-K(+)-2Cl(-) cotransporter.";
RL J. Am. Soc. Nephrol. 27:107-119(2016).
CC -!- FUNCTION: Renal sodium, potassium and chloride ion cotransporter that
CC mediates the transepithelial NaCl reabsorption in the thick ascending
CC limb and plays an essential role in the urinary concentration and
CC volume regulation. Electrically silent transporter system.
CC {ECO:0000305|PubMed:25967121}.
CC -!- ACTIVITY REGULATION: Activated by WNK3. {ECO:0000250}.
CC -!- SUBUNIT: When phosphorylated, interacts with PPP3CB.
CC {ECO:0000269|PubMed:25967121}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P55014}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in kidney (at protein
CC level). {ECO:0000269|PubMed:25967121, ECO:0000269|PubMed:8021284}.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U10096; AAA21251.1; -; mRNA.
DR PIR; A54145; A54145.
DR AlphaFoldDB; P55016; -.
DR SMR; P55016; -.
DR STRING; 10116.ENSRNOP00000008857; -.
DR TCDB; 2.A.30.1.1; the cation-chloride cotransporter (ccc) family.
DR GlyGen; P55016; 2 sites.
DR iPTMnet; P55016; -.
DR PhosphoSitePlus; P55016; -.
DR PaxDb; P55016; -.
DR PRIDE; P55016; -.
DR UCSC; RGD:3685; rat.
DR RGD; 3685; Slc12a1.
DR eggNOG; KOG2083; Eukaryota.
DR InParanoid; P55016; -.
DR PhylomeDB; P55016; -.
DR Reactome; R-RNO-426117; Cation-coupled Chloride cotransporters.
DR PRO; PR:P55016; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0008511; F:sodium:potassium:chloride symporter activity; IDA:RGD.
DR GO; GO:0006884; P:cell volume homeostasis; 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:0006821; P:chloride transport; IDA:RGD.
DR GO; GO:0016101; P:diterpenoid metabolic process; IEP:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; ISO:RGD.
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 GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR GO; GO:0032978; P:protein insertion into membrane from inner side; IDA:RGD.
DR GO; GO:0070294; P:renal sodium ion absorption; IC:BHF-UCL.
DR GO; GO:0055078; P:sodium ion homeostasis; IBA:GO_Central.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR GO; GO:0071918; P:urea transmembrane transport; ISO:RGD.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR013612; AA_permease_N.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR002445; Slc12a1.
DR InterPro; IPR002443; SLC12A1/SLC12A2.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR Pfam; PF00324; AA_permease; 1.
DR Pfam; PF08403; AA_permease_N; 1.
DR Pfam; PF03522; SLC12; 1.
DR PRINTS; PR01207; NAKCLTRNSPRT.
DR PRINTS; PR01209; NAKCLTRSPRT2.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Chloride; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome; Sodium;
KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1095
FT /note="Solute carrier family 12 member 1"
FT /id="PRO_0000178021"
FT TOPO_DOM 1..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..218
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 219..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..344
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..546
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 547..567
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 568..588
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 589..605
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 606..626
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 789..809
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 810..1095
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 26..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 96
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 101
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 114
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 126
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:17341212"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 452
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 96
FT /note="T->A: Loss of interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
FT MUTAGEN 96
FT /note="T->D: No effect on interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
FT MUTAGEN 101
FT /note="T->A: Loss of interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
FT MUTAGEN 101
FT /note="T->D: No effect on interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
FT MUTAGEN 114
FT /note="T->A: Loss of interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
FT MUTAGEN 114
FT /note="T->D: No effect on interaction with PPP3CB."
FT /evidence="ECO:0000269|PubMed:25967121"
SQ SEQUENCE 1095 AA; 120597 MW; 93C46F6ACD44363C CRC64;
MSVNIPSNSV PSGASRFQVH VINEGHGSGA AMSDSTDPPH YEETSFGDEA QNRLKISFRP
GNQECYENFL QTGETAKTDT TFHAYDSHTN TYYLQTFGHN TMDAVPKIEY YRNTGSVSGP
KVNRPSLQEI HEQLAKNVAV APGSADRVAN GDGMPGDEQA ENKEEDVTGV VKFGWVKGVL
VRCMLNIWGV MLFIRLSWIV GEAGIGLGVI IIGLSVVVTT LTGISMSAIC TNGVVRGGGA
YYLISRSLGP EFGGSIGLIF RFANAVRVAM YVVGFAETVV DLLKESDSMM VDPTNDIRII
GSITVVILLG ISVAGMEWEA KAQVILLVIL LIGIANFFIG TVIPSNNEKK SRGFFNYQAS
IFAENFGPSF TEGEGFFSVF AIFFPAATGI LAGANISGDL EDPQDAIPRG TMLAIFITTV
AYIGVAICVR ACVVRDATGS MNDTVVSGMN CNGSAACGLG YDFSRCQHEP CQYGLMNNFQ
VMSMVSGFGP LITAGIFSAT LSSALASLVS APKVFQALCK DNIFKGLQFF AKGYGKNNEP
LRGYFLTFVI AMAFILIAEL NVIAPIISNF FLASYALINF SCFHASYAKS PGWRPAYGIY
NMWVSLFGAI LCCAVMFVIN WWAAVITYVI ELFLYIYVTY KKPDVNWGSS TQALSYVSAL
DNALELTTVE DHVKNFRPQC IVLTGGPMTR PALLDITHAF TKNSGLCICC EVFVGPRKLC
VKEMNSGMAK KQAWLMKNKI KAFYAAVAAD CFRDGVRSLL QASGLGRMKP NTLVIGYKKN
WRKAPLSELE NYVGIIHDAF DFEIGVVIVR ISQGFDISPV LQVQDELEKL EQERLALEAA
IKDNDCEEGK GGIRGLFKKA GKLNITKPAP KKDSNISTIQ SMHVGEFNQK LVEASAQFKK
KQGKGTIDVW WLFDDGGLTL LIPYILTLRK KWKDCKLRIY VGGKINRIEE EKISMASLLS
KFRIKFADIH IIGDINIKPN KESWKVFEEM IEPYRLHESH KDLTTAEKLK RESPWKITDA
ELEAVKEKSY RQVRLNELLQ EHSRAANLIV LSLPVARKGS ISDLLYMAWL EILTKNLPPV
LLVRGNHKNV LTFYS
