S12A1_RABIT
ID S12A1_RABIT Reviewed; 1099 AA.
AC P55015;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Solute carrier family 12 member 1;
DE AltName: Full=Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2;
DE AltName: Full=Kidney-specific Na-K-Cl symporter;
GN Name=SLC12A1; Synonyms=NKCC2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND F).
RC STRAIN=New Zealand white; TISSUE=Kidney;
RX PubMed=7514306; DOI=10.1073/pnas.91.10.4544;
RA Payne J.A., Forbush B. III;
RT "Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter
RT are differentially distributed within the rabbit kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:4544-4548(1994).
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:0000250|UniProtKB:P55016}.
CC -!- ACTIVITY REGULATION: Activated by WNK3. {ECO:0000250}.
CC -!- SUBUNIT: When phosphorylated, interacts with PPP3CB.
CC {ECO:0000250|UniProtKB:P55016}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P55014}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=P55015-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P55015-2; Sequence=VSP_006103;
CC Name=F;
CC IsoId=P55015-3; Sequence=VSP_006104;
CC -!- TISSUE SPECIFICITY: Predominant in kidney. The 3 isoforms are
CC differentially distributed within the kidney: B almost exclusively in
CC cortex, F almost exclusively in medulla, and A about equally
CC distributed.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U07547; AAC48591.1; -; mRNA.
DR EMBL; U07548; AAB03494.1; -; mRNA.
DR EMBL; U07549; AAC48592.1; -; mRNA.
DR PIR; I46496; I46496.
DR PIR; I46497; I46497.
DR PIR; I46498; I46498.
DR RefSeq; NP_001164442.1; NM_001170971.1. [P55015-1]
DR AlphaFoldDB; P55015; -.
DR SMR; P55015; -.
DR STRING; 9986.ENSOCUP00000014189; -.
DR iPTMnet; P55015; -.
DR PRIDE; P55015; -.
DR GeneID; 100328575; -.
DR KEGG; ocu:100328575; -.
DR CTD; 6557; -.
DR eggNOG; KOG2083; Eukaryota.
DR InParanoid; P55015; -.
DR OrthoDB; 254933at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015377; F:cation:chloride symporter activity; IEA:InterPro.
DR GO; GO:0006813; P:potassium ion transport; IEA:UniProtKB-KW.
DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Chloride; Glycoprotein; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium transport;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1099
FT /note="Solute carrier family 12 member 1"
FT /id="PRO_0000178020"
FT TOPO_DOM 1..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 401..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 506..550
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 551..571
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 572..592
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 593..609
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 610..630
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 793..813
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 814..1099
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 147..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 99
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 104
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 117
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT MOD_RES 129
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 213..238
FT /note="VVIILLSTMVTSITGLSTSAIATNGF -> VIIIGLAVTVTGITGLSTSAIA
FT TNGY (in isoform B)"
FT /evidence="ECO:0000303|PubMed:7514306"
FT /id="VSP_006103"
FT VAR_SEQ 213..238
FT /note="VVIILLSTMVTSITGLSTSAIATNGF -> IIVIGLSVVVTTLTGISMSAIC
FT TNGV (in isoform F)"
FT /evidence="ECO:0000303|PubMed:7514306"
FT /id="VSP_006104"
SQ SEQUENCE 1099 AA; 121471 MW; 44281CE8C6F2FEE7 CRC64;
MSLNNSSSVF LDSVPTNTNR FQVNVINENH ESCAAGIDNT DPPHYEETSF GDEQNRLRIS
FRPGNQECYD NFLQTGETTK TDASFHTYDS HTNTYYLQTF GHNTMDAVPK IEYYRNTGSV
SGPKVNRPSL LEIHEQLAKN VAVTPGSADR VANGEGMPGE EHAENKEEDN KAGAVKFGWV
KGVLVRCMLN IWGVMLFIRL SWIVGEAGIG LGVVIILLST MVTSITGLST SAIATNGFVR
GGGAYYLISR SLGPEFGGSI GLIFAFANAV AVAMYVVGFA ETVVDLLKES DSMMVDPTND
IRIIGSITVV ILLGISVAGM EWEAKAQVIL LIILLIAIAN FFIGTVIPSN NEKKSRGFFN
YQASIFAENF GPSFTKGEGF FSVFAIFFPA ATGILAGANI SGDLEDPQDA IPRGTMLAIF
ITTVAYIGVA ICVGACVVRD ATGSMNDTII SGINCNGSAA CGLGYDFSRC RHEPCQYGLM
NNFQVMSMVS GFGPLITAGI FSATLSSALA SLVSAAKVFQ ALCKDNIYKA LQFFAKGYGK
NNEPLRGYIL TFVIAMAFIL IAELNTIAPI ISNFFLASYA LINFSCFHAS YAKSPGWRPA
YGIYNMWVSL FGAVLCCAVM FVINWWAAVI TYVIEFFLYI YVTYKKPDVN WGSSTQALSY
VSALDNALEL TTVEDHVKNF RPQCFVLTGG PMTRPALLDI TYAFTKNSGL CICCEVFVGP
RKLCVKEMNS GMAKKQAWLI KNKIKAFYAA VAADCFRDGV RSLLQASGLG RMKPNTLVIG
YKKKWRKAPL TEIENYVGII HDAFDFEIGV VIVRISQGFD ISQVLQVQEE LEKLEQERLA
LEATIKDNEC EEGNGGIRGL FKKVGKLNIT KPTPKKDSSI NTIQSMHVGE FNQKLVEAST
QFKKKQGKGT IDVWWLFDDG GLTLLIPYIL TLRKKWKDCK LRIYVGGKIN RIEEEKIAMA
SLLSKFRIKF ADIHVIGDIN IKPNKESWKF FEEMIEPYRL HESCKDLTTA EKLKRETPWK
ITDAELEAVK EKSYRQVRLN ELLQEHSRAA NLIVLSLPVA RKGSISDLLY MAWLEILTKN
LPPVLLVRGN HKNVLTFYS
