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Protein

Solute carrier family 12 member 3

Gene

Slc12a3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Electrically silent transporter system. Mediates sodium and chloride reabsorption (By similarity).By similarity

Enzyme regulationi

Activated by WNK3.By similarity

GO - Molecular functioni

  1. cation:chloride symporter activity Source: InterPro
  2. transporter activity Source: UniProtKB

GO - Biological processi

  1. sodium ion transport Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiREACT_247880. Cation-coupled Chloride cotransporters.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 3
Alternative name(s):
Na-Cl symporter
Thiazide-sensitive sodium-chloride cotransporter
Gene namesi
Name:Slc12a3
Synonyms:Ncc, Tsc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:108114. Slc12a3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 133133CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei134 – 15421HelicalSequence AnalysisAdd
BLAST
Transmembranei165 – 18521HelicalSequence AnalysisAdd
BLAST
Topological domaini186 – 21631CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei217 – 23721HelicalSequence AnalysisAdd
BLAST
Transmembranei260 – 28021HelicalSequence AnalysisAdd
BLAST
Topological domaini281 – 2844CytoplasmicSequence Analysis
Transmembranei285 – 30521HelicalSequence AnalysisAdd
BLAST
Transmembranei338 – 35821HelicalSequence AnalysisAdd
BLAST
Topological domaini359 – 37517CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei376 – 39621HelicalSequence AnalysisAdd
BLAST
Transmembranei451 – 47121HelicalSequence AnalysisAdd
BLAST
Topological domaini472 – 50938CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei510 – 53021HelicalSequence AnalysisAdd
BLAST
Transmembranei576 – 59621HelicalSequence AnalysisAdd
BLAST
Topological domaini597 – 65862CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei659 – 67921HelicalSequence AnalysisAdd
BLAST
Transmembranei811 – 83121HelicalSequence AnalysisAdd
BLAST
Topological domaini832 – 1002171CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: UniProtKB
  2. cytosol Source: UniProtKB
  3. extracellular vesicular exosome Source: MGI
  4. integral component of membrane Source: UniProtKB-KW
  5. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10021002Solute carrier family 12 member 3PRO_0000178027Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi404 – 4041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi424 – 4241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi542 – 5421N-linked (GlcNAc...)Sequence Analysis
Glycosylationi779 – 7791N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Ubiquitinated; ubiquitination is essential for regulation of endocytosis.1 Publication

Keywords - PTMi

Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP59158.
PRIDEiP59158.

PTM databases

PhosphoSiteiP59158.

Expressioni

Gene expression databases

BgeeiP59158.
CleanExiMM_SLC12A3.
ExpressionAtlasiP59158. baseline.
GenevestigatoriP59158.

Interactioni

Subunit structurei

Interacts with KLHL3.By similarity

Protein-protein interaction databases

BioGridi203278. 4 interactions.
IntActiP59158. 1 interaction.
MINTiMINT-4133700.

Structurei

3D structure databases

ProteinModelPortaliP59158.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP59158.
KOiK14426.
OMAiQLYPLIG.
OrthoDBiEOG75MVVC.
PhylomeDBiP59158.
TreeFamiTF313191.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR004842. Na/K/Cl_cotransptS.
IPR002948. SLC12A3.
[Graphical view]
PANTHERiPTHR11827:SF9. PTHR11827:SF9. 1 hit.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSiPR01230. NACLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequencei

Sequence statusi: Complete.

P59158-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,002
Mass (Da):110,694
Last modified:December 13, 2002 - v1
Checksum:i61CB02500C9093B9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC038612 mRNA. Translation: AAH38612.1.
CCDSiCCDS57632.1.
RefSeqiNP_001192240.1. NM_001205311.1.
UniGeneiMm.25804.

Genome annotation databases

EnsembliENSMUST00000034218; ENSMUSP00000034218; ENSMUSG00000031766.
GeneIDi20497.
KEGGimmu:20497.
UCSCiuc009mwc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC038612 mRNA. Translation: AAH38612.1.
CCDSiCCDS57632.1.
RefSeqiNP_001192240.1. NM_001205311.1.
UniGeneiMm.25804.

3D structure databases

ProteinModelPortaliP59158.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203278. 4 interactions.
IntActiP59158. 1 interaction.
MINTiMINT-4133700.

PTM databases

PhosphoSiteiP59158.

Proteomic databases

PaxDbiP59158.
PRIDEiP59158.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034218; ENSMUSP00000034218; ENSMUSG00000031766.
GeneIDi20497.
KEGGimmu:20497.
UCSCiuc009mwc.2. mouse.

Organism-specific databases

CTDi6559.
MGIiMGI:108114. Slc12a3.

Phylogenomic databases

eggNOGiCOG0531.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP59158.
KOiK14426.
OMAiQLYPLIG.
OrthoDBiEOG75MVVC.
PhylomeDBiP59158.
TreeFamiTF313191.

Enzyme and pathway databases

ReactomeiREACT_247880. Cation-coupled Chloride cotransporters.

Miscellaneous databases

ChiTaRSiSlc12a3. mouse.
NextBioi298655.
PROiP59158.
SOURCEiSearch...

Gene expression databases

BgeeiP59158.
CleanExiMM_SLC12A3.
ExpressionAtlasiP59158. baseline.
GenevestigatoriP59158.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR004842. Na/K/Cl_cotransptS.
IPR002948. SLC12A3.
[Graphical view]
PANTHERiPTHR11827:SF9. PTHR11827:SF9. 1 hit.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSiPR01230. NACLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Kidney.
  2. "RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter."
    Ko B., Kamsteeg E.J., Cooke L.L., Moddes L.N., Deen P.M., Hoover R.S.
    Am. J. Physiol. 299:F300-F309(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION.

Entry informationi

Entry nameiS12A3_MOUSE
AccessioniPrimary (citable) accession number: P59158
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 13, 2002
Last modified: February 4, 2015
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.