UniProtKB - P59158 (S12A3_MOUSE)
Protein
Solute carrier family 12 member 3
Gene
Slc12a3
Organism
Mus musculus (Mouse)
Status
Functioni
Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (By similarity). Receptor for the proinflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (PubMed:26099046).By similarity1 Publication
Activity regulationi
Activated by WNK3.By similarity
GO - Molecular functioni
- enzyme binding Source: MGI
- potassium:chloride symporter activity Source: GO_Central
- sodium:chloride symporter activity Source: MGI
- sodium:potassium:chloride symporter activity Source: GO_Central
- sodium ion transmembrane transporter activity Source: UniProtKB
GO - Biological processi
- cell volume homeostasis Source: GO_Central
- chloride ion homeostasis Source: GO_Central
- chloride transmembrane transport Source: GO_Central
- chloride transport Source: MGI
- potassium ion homeostasis Source: GO_Central
- potassium ion import across plasma membrane Source: GO_Central
- sodium ion homeostasis Source: GO_Central
- sodium ion transmembrane transport Source: MGI
- sodium ion transport Source: UniProtKB
Keywordsi
Biological process | Ion transport, Sodium transport, Symport, Transport |
Ligand | Chloride, Sodium |
Enzyme and pathway databases
Reactomei | R-MMU-426117, Cation-coupled Chloride cotransporters |
Names & Taxonomyi
Protein namesi | Recommended name: Solute carrier family 12 member 3Alternative name(s): Na-Cl symporter Thiazide-sensitive sodium-chloride cotransporter |
Gene namesi | Name:Slc12a3 Synonyms:Ncc, Tsc |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:108114, Slc12a3 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein
Cytosol
- cytosol Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: MGI
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
- vesicle Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 133 | CytoplasmicSequence analysisAdd BLAST | 133 | |
Transmembranei | 134 – 154 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 165 – 185 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 186 – 216 | CytoplasmicSequence analysisAdd BLAST | 31 | |
Transmembranei | 217 – 237 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 260 – 280 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 281 – 284 | CytoplasmicSequence analysis | 4 | |
Transmembranei | 285 – 305 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 338 – 358 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 359 – 375 | CytoplasmicSequence analysisAdd BLAST | 17 | |
Transmembranei | 376 – 396 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 451 – 471 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 472 – 509 | CytoplasmicSequence analysisAdd BLAST | 38 | |
Transmembranei | 510 – 530 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 576 – 596 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 597 – 658 | CytoplasmicSequence analysisAdd BLAST | 62 | |
Transmembranei | 659 – 679 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 811 – 831 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 832 – 1002 | CytoplasmicSequence analysisAdd BLAST | 171 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Simultaneous knockout of APOE and SLC12A3 results lower plasma Mg2+ compared to plasma levels in wild-type and APOE knockout animals. Simultaneous knockdown of APOE and SLC12A3 shows no significant differences in aortic root atherosclerotic lesion intima area and thoracic-abdominal aorta lipid deposition as compared to APOE and double APOE and IL18R1 knockout animals. In contrast, simultaneous knockdown of APOE, SLC12A3 and IL18R1 results in significantly smaller aortic root intimal size and decreased thoracic-abdominal aorta lipid deposition. The triple knockout mice exhibit lower plasma K+ and Mg2+ compared to plasma levels in wild-type animals. The effect on atherosclerosis is due to IL18 activation of bone marrow-derived leukocytes, and possibly vascular cells, rather than to kidney tubular disorders or electrolyte disturbances.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 53 | T → A: Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12. 1 Publication | 1 | |
Mutagenesisi | 58 | T → A: No effect on MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12. Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12; when associated with A-53 and A-71. 1 Publication | 1 | |
Mutagenesisi | 71 | S → A: No effect on MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12. Substantial reduction in MAPK1/3 (ERK1/2) phosphorylation in response to IL18, with or without IL12; when associated with A-53 and A-58. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000178027 | 1 – 1002 | Solute carrier family 12 member 3Add BLAST | 1002 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 41 | PhosphoserineCombined sources | 1 | |
Modified residuei | 47 | PhosphoserineCombined sources | 1 | |
Modified residuei | 48 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 53 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 58 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 71 | PhosphoserineCombined sources | 1 | |
Modified residuei | 89 | PhosphoserineBy similarity | 1 | |
Modified residuei | 122 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 124 | PhosphoserineCombined sources | 1 | |
Glycosylationi | 404 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 424 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 542 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 779 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Ubiquitinated; ubiquitination is essential for regulation of endocytosis.1 Publication
Phosphorylated in response to IL18.1 Publication
Keywords - PTMi
Glycoprotein, Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | P59158 |
PaxDbi | P59158 |
PeptideAtlasi | P59158 |
PRIDEi | P59158 |
PTM databases
GlyGeni | P59158, 4 sites |
iPTMneti | P59158 |
PhosphoSitePlusi | P59158 |
Expressioni
Tissue specificityi
Expressed predominantly in kidney, including in distal tubules (at protein level). Detected at low levels in heart, lung and liver. Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions. In atherosclerotic lesions, expressed in macrophages, smooth muscle cells and endothelial cells (at protein level).1 Publication
Inductioni
In macrophages and T-lymphocytes, up-regulated by IL18. In endothelial cells and smooth muscle cells, up-regulated by IL1B, IL18 and TNF (at protein level).1 Publication
Gene expression databases
Bgeei | ENSMUSG00000031766, Expressed in cortex of kidney and 49 other tissues |
ExpressionAtlasi | P59158, baseline and differential |
Genevisiblei | P59158, MM |
Interactioni
Subunit structurei
Interacts with KLHL3 (By similarity).
Interacts with IL18R1 in peritoneal macrophages; this interaction is increased by IL18 treatment (PubMed:26099046).
By similarity1 PublicationBinary interactionsi
P59158
With | #Exp. | IntAct |
---|---|---|
Il18r1 [Q61098] | 5 | EBI-8366645,EBI-13612516 |
GO - Molecular functioni
- enzyme binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 203278, 2 interactors |
IntActi | P59158, 2 interactors |
MINTi | P59158 |
STRINGi | 10090.ENSMUSP00000034218 |
Miscellaneous databases
RNActi | P59158, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the SLC12A transporter family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2083, Eukaryota |
GeneTreei | ENSGT00940000155044 |
HOGENOMi | CLU_001883_0_0_1 |
InParanoidi | P59158 |
OrthoDBi | 254933at2759 |
PhylomeDBi | P59158 |
TreeFami | TF313191 |
Family and domain databases
InterProi | View protein in InterPro IPR004841, AA-permease/SLC12A_dom IPR013612, AA_permease_N IPR018491, SLC12_C IPR002948, SLC12A3 IPR004842, SLC12A_fam |
PANTHERi | PTHR11827:SF9, PTHR11827:SF9, 1 hit |
Pfami | View protein in Pfam PF00324, AA_permease, 1 hit PF08403, AA_permease_N, 1 hit PF03522, SLC12, 2 hits |
PRINTSi | PR01230, NACLTRNSPORT |
TIGRFAMsi | TIGR00930, 2a30, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P59158-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAELPVTELP GDALCSGRFT ISTLMGGDEP PPAACDSSQP SHLTHGSTLY
60 70 80 90 100
MRTFGYNTID VVPAYEHYAN SALPGEPRKV RPTLADLHSF LKQEGSHLHA
110 120 130 140 150
LAFDGRQGRE LTDGLVEDET GTNSEKSPGE PVRFGWVKGV MIRCMLNIWG
160 170 180 190 200
VILYLRLPWI TAQAGIVLTW LIILLSVMVT SITGLSISAI STNGKVKSGG
210 220 230 240 250
TYFLISRSLG PELGGSIGLI FAFANAVGVA MHTVGFAETV RDLLQEYGTP
260 270 280 290 300
IVDPINDIRI IGVVTVTVLL AISLAGMEWE SKAQVLFFLV IMVSFANYLV
310 320 330 340 350
GTLIPASEDK ASKGFYSYHG DIFVQNLVPD WRGIDGSFFG MFSIFFPSAT
360 370 380 390 400
GILAGANISG DLKDPAVAIP KGTLMAIFWT TISYLAISAT IGSCVVRDAS
410 420 430 440 450
GDVNDTMTPG PGPCEGLACG YGWNFTECSQ QRSCRYGLIN YYQTMSMVSA
460 470 480 490 500
FAPLITAGIF GATLSSALAC LVSAAKVFQC LCEDQLYPLI GFFGKGYGKN
510 520 530 540 550
REPVRGYLLA YAIAVAFIII AELNTIAPII SNFFLCSYAL INFSCFHASI
560 570 580 590 600
TNSPGWRPSF RYYSKWAALF GAVISVVIMF LLTWWAALIA IGVVLFLLLY
610 620 630 640 650
VIYKKPEVNW GSSVQAGSYN LALSYSVGLN EVEDHIKNYR PQCLVLTGPP
660 670 680 690 700
NFRPALVDFV STFTQNLSLM ICGHVLIGPG KQRVPELRLI ASGHTKWLNK
710 720 730 740 750
RKIKAFYSDV IAEDLRSGVQ ILMQASGLGR MKPNILVVGF KRNWQSAHPA
760 770 780 790 800
TVEDYIGVLH DAFDFNYGVC VMRMREGLNV SEALQTHTTP EALIQEEQAS
810 820 830 840 850
TIFQSEQGKK TIDIYWLFDD GGLTLLIPYL LHRKKRWGKC KIRVFVGGQI
860 870 880 890 900
NRMDEERKAI ISLLSKFRLG FHEVHVLPDI NQKPQAEHTK RFEDMIAPFR
910 920 930 940 950
LNDGFKDEAT VTEMRRDCPW KISDEEINKN RIKSLRQVRL SEILLDYSRD
960 970 980 990 1000
AALIILTLPI GRKGKCPSSL YMAWLETLSQ DLRPPVLLIR GNQENVLTFY
CQ
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1D5RLP7 | A0A1D5RLP7_MOUSE | Solute carrier family 12 member 3 | Slc12a3 | 956 | Annotation score: | ||
A0A1D5RLX1 | A0A1D5RLX1_MOUSE | Solute carrier family 12 member 3 | Slc12a3 | 130 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC038612 mRNA Translation: AAH38612.1 |
CCDSi | CCDS57632.1 |
RefSeqi | NP_001192240.1, NM_001205311.1 |
Genome annotation databases
Ensembli | ENSMUST00000034218; ENSMUSP00000034218; ENSMUSG00000031766 |
GeneIDi | 20497 |
KEGGi | mmu:20497 |
UCSCi | uc009mwc.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC038612 mRNA Translation: AAH38612.1 |
CCDSi | CCDS57632.1 |
RefSeqi | NP_001192240.1, NM_001205311.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 203278, 2 interactors |
IntActi | P59158, 2 interactors |
MINTi | P59158 |
STRINGi | 10090.ENSMUSP00000034218 |
PTM databases
GlyGeni | P59158, 4 sites |
iPTMneti | P59158 |
PhosphoSitePlusi | P59158 |
Proteomic databases
jPOSTi | P59158 |
PaxDbi | P59158 |
PeptideAtlasi | P59158 |
PRIDEi | P59158 |
Protocols and materials databases
Antibodypediai | 28680, 251 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000034218; ENSMUSP00000034218; ENSMUSG00000031766 |
GeneIDi | 20497 |
KEGGi | mmu:20497 |
UCSCi | uc009mwc.2, mouse |
Organism-specific databases
CTDi | 6559 |
MGIi | MGI:108114, Slc12a3 |
Phylogenomic databases
eggNOGi | KOG2083, Eukaryota |
GeneTreei | ENSGT00940000155044 |
HOGENOMi | CLU_001883_0_0_1 |
InParanoidi | P59158 |
OrthoDBi | 254933at2759 |
PhylomeDBi | P59158 |
TreeFami | TF313191 |
Enzyme and pathway databases
Reactomei | R-MMU-426117, Cation-coupled Chloride cotransporters |
Miscellaneous databases
BioGRID-ORCSi | 20497, 0 hits in 17 CRISPR screens |
ChiTaRSi | Slc12a3, mouse |
PROi | PR:P59158 |
RNActi | P59158, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031766, Expressed in cortex of kidney and 49 other tissues |
ExpressionAtlasi | P59158, baseline and differential |
Genevisiblei | P59158, MM |
Family and domain databases
InterProi | View protein in InterPro IPR004841, AA-permease/SLC12A_dom IPR013612, AA_permease_N IPR018491, SLC12_C IPR002948, SLC12A3 IPR004842, SLC12A_fam |
PANTHERi | PTHR11827:SF9, PTHR11827:SF9, 1 hit |
Pfami | View protein in Pfam PF00324, AA_permease, 1 hit PF08403, AA_permease_N, 1 hit PF03522, SLC12, 2 hits |
PRINTSi | PR01230, NACLTRNSPORT |
TIGRFAMsi | TIGR00930, 2a30, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | S12A3_MOUSE | |
Accessioni | P59158Primary (citable) accession number: P59158 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 13, 2002 |
Last sequence update: | December 13, 2002 | |
Last modified: | December 2, 2020 | |
This is version 136 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families