S12A3_RAT
ID S12A3_RAT Reviewed; 1002 AA.
AC P55018;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 13-DEC-2002, sequence version 2.
DT 25-MAY-2022, entry version 137.
DE RecName: Full=Solute carrier family 12 member 3;
DE AltName: Full=Na-Cl symporter;
DE AltName: Full=Thiazide-sensitive sodium-chloride cotransporter;
GN Name=Slc12a3; Synonyms=Tsc;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney cortex;
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).
CC -!- FUNCTION: Electroneutral sodium and chloride ion cotransporter. In
CC kidney distal convoluted tubules, key mediator of sodium and chloride
CC reabsorption (PubMed:8021284). Receptor for the pro-inflammatory
CC cytokine IL18. Contributes to IL18-induced cytokine production,
CC including IFNG, IL6, IL18 and CCL2, either independently of IL18R1, or
CC as a complex with IL18R1 (By similarity).
CC {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:8021284}.
CC -!- ACTIVITY REGULATION: Activated by WNK3. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with KLHL3 (By similarity). Interacts with IL18R1;
CC this interaction is increased by IL18 treatment (By similarity).
CC {ECO:0000250|UniProtKB:P55017, ECO:0000250|UniProtKB:P59158}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P55017};
CC Multi-pass membrane protein {ECO:0000255}. Apical cell membrane
CC {ECO:0000250|UniProtKB:P59158}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, predominantly in the outer
CC cortex in short tubule segments. {ECO:0000269|PubMed:8021284}.
CC -!- PTM: Ubiquitinated; ubiquitination is essential for regulation of
CC endocytosis. {ECO:0000250|UniProtKB:P59158}.
CC -!- PTM: Phosphorylated in response to IL18.
CC {ECO:0000250|UniProtKB:P59158}.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U10097; AAA21252.2; -; mRNA.
DR PIR; B54145; B54145.
DR RefSeq; NP_062218.3; NM_019345.3.
DR AlphaFoldDB; P55018; -.
DR SMR; P55018; -.
DR BioGRID; 248520; 3.
DR STRING; 10116.ENSRNOP00000025377; -.
DR TCDB; 2.A.30.1.11; the cation-chloride cotransporter (ccc) family.
DR GlyGen; P55018; 2 sites.
DR iPTMnet; P55018; -.
DR PhosphoSitePlus; P55018; -.
DR PaxDb; P55018; -.
DR PRIDE; P55018; -.
DR GeneID; 54300; -.
DR KEGG; rno:54300; -.
DR UCSC; RGD:3686; rat.
DR CTD; 6559; -.
DR RGD; 3686; Slc12a3.
DR eggNOG; KOG2083; Eukaryota.
DR InParanoid; P55018; -.
DR OrthoDB; 254933at2759; -.
DR PhylomeDB; P55018; -.
DR Reactome; R-RNO-426117; Cation-coupled Chloride cotransporters.
DR PRO; PR:P55018; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISO: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:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:RGD.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0015081; F:sodium ion transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015378; F:sodium:chloride symporter activity; IDA:RGD.
DR GO; GO:0008511; F:sodium:potassium:chloride symporter activity; IBA:GO_Central.
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; IMP: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: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; IDA:BHF-UCL.
DR GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR013612; AA_permease_N.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR002948; SLC12A3.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR PANTHER; PTHR11827:SF9; PTHR11827:SF9; 1.
DR Pfam; PF00324; AA_permease; 1.
DR Pfam; PF08403; AA_permease_N; 1.
DR Pfam; PF03522; SLC12; 2.
DR PRINTS; PR01230; NACLTRNSPORT.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Chloride; Glycoprotein; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sodium; Sodium transport; Symport;
KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..1002
FT /note="Solute carrier family 12 member 3"
FT /id="PRO_0000178028"
FT TOPO_DOM 1..133
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 217..237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..284
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..509
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 531..551
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 552..575
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 659..679
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 680..1002
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 48
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 53
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55017"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P59158"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 424
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1002 AA; 110554 MW; 1EAC70E86D542C9D CRC64;
MAELPVTEMP GDALCSGRFT ISTLLGGDEP PPAACDNSQP SHLTHGSTLY LRTFGYNTID
VVPAYEHYAN SALPGEPRKV RPTLADLHSF LKQEGSHLHA LAFDGRPGHE LTDGLVEDET
GANSEKSPGE PVRFGWVKGV MIRCMLNIWG VILYLRLPWI TAQAGIVLTW LIILLSVMVT
SITGLSISAI STNGKVKSGG TYFLISRSLG PELGGSIGLI FAFANAVGVA MHTVGFAETV
RDLLQENGTP IVDPINDIRI IGVVTVTVLL AISLAGMEWE SKAQVLFFLV IMVSFANYLV
GTLIPASKDK ASKGFYSYHG DIFVQNLVPD WRGIDGSFFG MFSIFFPSAT GILAGANISG
DLKDPAVAIP KGTLMAIFWT TISYLAISAT IGSCVVRDAS GDVNDTITPG PGLCEGLACG
YGWNFTECSQ QHSCRYGLIN YYQTMSMVSA FAPLITAGIF GATLSSALAC LVSAAKVFQC
LCEDQLYPLI GFFGKGYGKN KEPVRGYLLA YAIAVAFIII AELNTIAPII SNFFLCSYAL
INFSCFHASI TNSPGWRPSF RYYSKWAALF GAVISVVIMF LLTWWAALIA IGVVLFLLLY
VIYKKPEVNW GSSVQAGSYN LALSYSVGLN EVEDHIKNYR PQCLVLTGPP NFRPALVDFV
STFTQNLSLM ICGHVLIAPG KQRVPELRLI ASGHTKWLNK RKIKAFYSDV IAEDLRSGVQ
ILMQASGLGR MKPNILVVGF KKNWQSAHPA TLEDYIGILH DAFDFNYGVC IMRMREGLNV
SEALQTHTAP EALVQEEQTS TIFQSEQGKK TIDIYWLFDD GGLTLLIPYL LHRKKRWGKC
KIRVFVGGQI NRMDEERKAI ISLLSKFRLG FHEVHVLPDI NQKPQVEHTK RFEDMIAPFR
LNDGFKDEAT VAEMRRDYPW KISDEEINKN RIKSLRQVRL NEILLDYSRD AALIILTLPI
GRKGKCPSSL YMAWLETLSQ DLSPPVLLIR GNQENVLTFY CQ
