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Protein

Solute carrier family 26 member 6

Gene

Slc26a6

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

Functioni

Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Function in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.17 Publications

Enzyme regulationi

Apical membrane chloride-bicarbonate exchange activity of the pancreatic duct is inhibited by DIDS (By similarity). Apical membrane chloride-formate exchange activity in the proximal tubules of the kidney and oxalate secretion in the duodenum are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters).By similarity6 Publications

Kineticsi

  1. KM=0.3 mM for oxalate, PubMed:121192872 Publications
  2. KM=0.314 mM for oxalate, PubMed:152039032 Publications
  3. KM=3.87 mM for formate, PubMed:152039032 Publications

    GO - Molecular functioni

    • anion:anion antiporter activity Source: UniProtKB
    • bicarbonate transmembrane transporter activity Source: UniProtKB
    • chloride channel activity Source: GO_Central
    • chloride transmembrane transporter activity Source: UniProtKB
    • efflux transmembrane transporter activity Source: UniProtKB
    • formate efflux transmembrane transporter activity Source: UniProtKB
    • formate transmembrane transporter activity Source: UniProtKB
    • formate uptake transmembrane transporter activity Source: UniProtKB
    • oxalate transmembrane transporter activity Source: UniProtKB
    • PDZ domain binding Source: UniProtKB
    • secondary active sulfate transmembrane transporter activity Source: InterPro
    • sulfate transmembrane transporter activity Source: UniProtKB

    GO - Biological processi

    • angiotensin-activated signaling pathway Source: UniProtKB
    • bicarbonate transport Source: UniProtKB
    • cellular response to cAMP Source: UniProtKB
    • cellular response to fructose stimulus Source: UniProtKB
    • cellular response to interferon-gamma Source: MGI
    • chloride transport Source: UniProtKB
    • epithelial fluid transport Source: UniProtKB
    • formate transport Source: UniProtKB
    • intestinal absorption Source: UniProtKB
    • intracellular pH elevation Source: UniProtKB
    • mannitol transport Source: UniProtKB
    • oxalate transport Source: UniProtKB
    • oxalic acid secretion Source: UniProtKB
    • positive regulation of dipeptide transmembrane transport Source: UniProtKB
    • protein kinase C signaling Source: UniProtKB
    • regulation of intracellular pH Source: UniProtKB
    • regulation of membrane potential Source: GO_Central
    • sperm capacitation Source: UniProtKB
    • sulfate transport Source: UniProtKB
    • transepithelial chloride transport Source: UniProtKB
    • transepithelial transport Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Chloride channel, Ion channel

    Keywords - Biological processi

    Anion exchange, Antiport, Ion transport, Transport

    Keywords - Ligandi

    Chloride

    Enzyme and pathway databases

    SABIO-RKQ8CIW6.

    Protein family/group databases

    TCDBi2.A.53.2.8. the sulfate permease (sulp) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Solute carrier family 26 member 6
    Alternative name(s):
    Anion exchange transporter
    Chloride-formate exchanger
    Pendrin-L1
    Pendrin-like protein 1
    Putative anion transporter-1
    Short name:
    Pat-1
    Gene namesi
    Name:Slc26a6Imported
    Synonyms:Cfex, Pat1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Unplaced

    Organism-specific databases

    MGIiMGI:2159728. Slc26a6.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 117CytoplasmicSequence analysisAdd BLAST117
    Transmembranei118 – 138HelicalSequence analysisAdd BLAST21
    Topological domaini139 – 187ExtracellularSequence analysisAdd BLAST49
    Transmembranei188 – 208HelicalSequence analysisAdd BLAST21
    Topological domaini209 – 263CytoplasmicSequence analysisAdd BLAST55
    Transmembranei264 – 284HelicalSequence analysisAdd BLAST21
    Topological domaini285 – 292ExtracellularSequence analysis8
    Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
    Topological domaini314 – 340CytoplasmicSequence analysisAdd BLAST27
    Transmembranei341 – 361HelicalSequence analysisAdd BLAST21
    Topological domaini362 – 380ExtracellularSequence analysisAdd BLAST19
    Transmembranei381 – 401HelicalSequence analysisAdd BLAST21
    Topological domaini402 – 417CytoplasmicSequence analysisAdd BLAST16
    Transmembranei418 – 438HelicalSequence analysisAdd BLAST21
    Topological domaini439 – 485ExtracellularSequence analysisAdd BLAST47
    Transmembranei486 – 506HelicalSequence analysisAdd BLAST21
    Topological domaini507 – 758CytoplasmicSequence analysisAdd BLAST252

    GO - Cellular componenti

    • apical plasma membrane Source: UniProtKB
    • basolateral plasma membrane Source: MGI
    • brush border membrane Source: UniProtKB
    • chloride channel complex Source: UniProtKB-KW
    • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
    • endoplasmic reticulum Source: UniProtKB-KW
    • integral component of membrane Source: MGI
    • integral component of plasma membrane Source: MGI
    • intracellular Source: GOC
    • membrane Source: UniProtKB
    • membrane-bounded vesicle Source: UniProtKB
    • plasma membrane Source: UniProtKB
    • sperm midpiece Source: UniProtKB
    • vesicle membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Disruption phenotypei

    Mice show an important decrease in salt absorption in the intestine and failed to develop hypertension on a high-fructose diet. Show a reduction in pancreatic duct fluid and bicarbonate secretion. Show enhanced oxalate absorption in the intestine leading to hyperoxalemia and hyperoxaluria with high incidence of calcium-oxalate stones formation.3 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi575T → A: Does not inhibit formate transport in PMA-induced cells. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004234231 – 758Solute carrier family 26 member 6Add BLAST758

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei603Phosphoserine; by PKCBy similarity1
    Modified residuei751PhosphoserineBy similarity1

    Post-translational modificationi

    Phosphorylated on serine residues by PKC; the phosphorylation disrupts interaction with carbonic anhydrase CA2 and reduces bicarbonate transport activity in a phorbol myristate acetate (PMA)-induced manner.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PeptideAtlasiQ8CIW6.
    PRIDEiQ8CIW6.

    PTM databases

    iPTMnetiQ8CIW6.
    PhosphoSitePlusiQ8CIW6.

    Expressioni

    Tissue specificityi

    Expressed in kidney (at protein level). Highly expressed in stomach, kidney, heart and small intestine, low in the lung, liver, testis, brain, skeletal muscle and colon. Expressed in spermatogenic cells. Isoform 1 is expressed in intestine, kidney, testis, brain, muscle, heart, and stomach.5 Publications

    Inductioni

    Up-regulated by dietary fructose intake (at protein level).1 Publication

    Interactioni

    Subunit structurei

    Interacts (via C-terminal cytoplasmic domain) with CA2; the interaction stimulates chloride-bicarbonate exchange activity. Interacts with SLC9A3R1 (via the PDZ domains). Interacts with SLC9A3R2 (via the PDZ domains) (By similarity). Interacts (via C-terminal domain) with PDZK1 (via C-terminal PDZ domain); the interaction induces chloride and oxalate exchange transport. Interacts with CFTR, SLC26A3 and SLC9A3R1. Interacts with AHCYL1; the interaction increases SLC26A6 activity (PubMed:23542070).By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CftrP263613EBI-6895517,EBI-6115317
    Slc26a3Q9WVC82EBI-6895517,EBI-6895537
    Slc9a3r1P704412EBI-6895517,EBI-1184085

    GO - Molecular functioni

    • PDZ domain binding Source: UniProtKB

    Protein-protein interaction databases

    IntActiQ8CIW6. 3 interactors.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CIW6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini531 – 741STASPROSITE-ProRule annotationAdd BLAST211

    Sequence similaritiesi

    Contains 1 STAS domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOGENOMiHOG000006546.
    HOVERGENiHBG000639.
    KOiK14704.
    TreeFamiTF313784.

    Family and domain databases

    Gene3Di3.30.750.24. 2 hits.
    InterProiIPR018045. S04_transporter_CS.
    IPR011547. SLC26A/SulP_dom.
    IPR001902. SLC26A/SulP_fam.
    IPR030323. SLC26A6.
    IPR002645. STAS_dom.
    [Graphical view]
    PANTHERiPTHR11814. PTHR11814. 2 hits.
    PTHR11814:SF113. PTHR11814:SF113. 2 hits.
    PfamiPF01740. STAS. 1 hit.
    PF00916. Sulfate_transp. 1 hit.
    [Graphical view]
    SUPFAMiSSF52091. SSF52091. 2 hits.
    TIGRFAMsiTIGR00815. sulP. 1 hit.
    PROSITEiPS01130. SLC26A. 1 hit.
    PS50801. STAS. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q8CIW6-1) [UniParc]FASTAAdd to basket
    Also known as: Slc26a6a

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGLPDGSDQG THQTQALLSA AQEMELQRRD YHVERPLLNQ EQLEDLGHWG
    60 70 80 90 100
    PAAKTHQWRT WFRCSRARAH SLLLQHVPVL GWLPRYPVRE WLLGDLLSGL
    110 120 130 140 150
    SVAIMQLPQG LAYALLAGLP PMFGLYSSFY PVFIYFLFGT SRHISVGTFA
    160 170 180 190 200
    VMSVMVGSVT ESLTADKAFV QGLNATADDA RVQVAYTLSF LVGLFQVGLG
    210 220 230 240 250
    LVHFGFVVTY LSEPLVRSYT TAASVQVLVS QLKYVFGIKL SSHSGPLSVI
    260 270 280 290 300
    YTVLEVCAQL PETVPGTVVT AIVAGVALVL VKLLNEKLHR RLPLPIPGEL
    310 320 330 340 350
    LTLIGATGIS YGVKLNDRFK VDVVGNITTG LIPPVAPKTE LFATLVGNAF
    360 370 380 390 400
    AIAVVGFAIA ISLGKIFALR HGYRVDSNQE LVALGLSNLI GGFFQCFPVS
    410 420 430 440 450
    CSMSRSLVQE STGGNTQVAG AVSSLFILLI IVKLGELFRD LPKAVLAAVI
    460 470 480 490 500
    IVNLKGMMKQ FSDICSLWKA NRVDLLIWLV TFVATILLNL DIGLAVSIVF
    510 520 530 540 550
    SLLLVVVRMQ LPHYSVLGQV PDTDIYRDVA EYSGAKEVPG VKVFRSSATL
    560 570 580 590 600
    YFANAELYSD SLKEKCGVDV DRLITQKKKR IKKQEMKLKR MKKAKKSQKQ
    610 620 630 640 650
    DASSKISSVS VNVNTNLEDV KSNDVEGSEA KVHQGEELQD VVSSNQEDAK
    660 670 680 690 700
    APTMTSLKSL GLPQPGFHSL ILDLSTLSFV DTVCIKSLKN IFRDFREIEV
    710 720 730 740 750
    EVYIAACYSP VVAQLEAGHF FDESITKQHV FASVHDAVTF ALSHRKSVPK

    SPVLATKL
    Length:758
    Mass (Da):82,834
    Last modified:September 18, 2013 - v2
    Checksum:i1512CC3A417D037B
    GO
    Isoform 2 (identifier: Q8CIW6-2) [UniParc]FASTAAdd to basket
    Also known as: Slc26a6b

    The sequence of this isoform differs from the canonical sequence as follows:
         1-23: Missing.

    Show »
    Length:735
    Mass (Da):80,496
    Checksum:i391DA011CB54C00A
    GO
    Isoform 3 (identifier: Q8CIW6-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-23: Missing.
         691-758: IFRDFREIEV...PKSPVLATKL → VRDCRQARAP...PALFVAADFP

    Show »
    Length:726
    Mass (Da):79,108
    Checksum:i8390F9A703F8EE94
    GO

    Sequence cautioni

    The sequence AC168054 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence CAAA01111125 differs from that shown. Reason: Erroneous gene model prediction.Curated
    The sequence CAAA01200220 differs from that shown. Reason: Erroneous gene model prediction.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti25E → G in AAK51131 (PubMed:11459928).Curated1
    Sequence conflicti25E → G in BAC55182 (PubMed:15203903).Curated1
    Sequence conflicti572R → P in AAL13129 (PubMed:12217875).Curated1
    Sequence conflicti572R → P in AAN07089 (PubMed:12217875).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0478531 – 23Missing in isoform 2 and isoform 3. 5 PublicationsAdd BLAST23
    Alternative sequenceiVSP_047854691 – 758IFRDF…LATKL → VRDCRQARAPQAFMLILPLA SHLLATPPPNKPSPLSSPTK PCPIAASLRPALFVAADFP in isoform 3. 1 PublicationAdd BLAST68

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY032863 mRNA. Translation: AAK51131.1.
    AF248494 mRNA. Translation: AAN07089.1.
    AY049076 mRNA. Translation: AAL13129.1.
    AB099881 mRNA. Translation: BAC55182.1.
    AK163670 mRNA. Translation: BAE37450.1.
    AK163671 mRNA. Translation: BAE37451.1.
    AC168054 Genomic DNA. No translation available.
    CAAA01111125 Genomic DNA. No translation available.
    CAAA01200220 Genomic DNA. No translation available.
    CH466560 Genomic DNA. Translation: EDL21319.1.
    BC028856 mRNA. Translation: AAH28856.1.
    RefSeqiNP_599252.2. NM_134420.4. [Q8CIW6-2]
    UniGeneiMm.45201.

    Genome annotation databases

    GeneIDi171429.
    KEGGimmu:171429.
    UCSCiuc009rrd.1. mouse. [Q8CIW6-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY032863 mRNA. Translation: AAK51131.1.
    AF248494 mRNA. Translation: AAN07089.1.
    AY049076 mRNA. Translation: AAL13129.1.
    AB099881 mRNA. Translation: BAC55182.1.
    AK163670 mRNA. Translation: BAE37450.1.
    AK163671 mRNA. Translation: BAE37451.1.
    AC168054 Genomic DNA. No translation available.
    CAAA01111125 Genomic DNA. No translation available.
    CAAA01200220 Genomic DNA. No translation available.
    CH466560 Genomic DNA. Translation: EDL21319.1.
    BC028856 mRNA. Translation: AAH28856.1.
    RefSeqiNP_599252.2. NM_134420.4. [Q8CIW6-2]
    UniGeneiMm.45201.

    3D structure databases

    ProteinModelPortaliQ8CIW6.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ8CIW6. 3 interactors.

    Protein family/group databases

    TCDBi2.A.53.2.8. the sulfate permease (sulp) family.

    PTM databases

    iPTMnetiQ8CIW6.
    PhosphoSitePlusiQ8CIW6.

    Proteomic databases

    PeptideAtlasiQ8CIW6.
    PRIDEiQ8CIW6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi171429.
    KEGGimmu:171429.
    UCSCiuc009rrd.1. mouse. [Q8CIW6-1]

    Organism-specific databases

    CTDi65010.
    MGIiMGI:2159728. Slc26a6.

    Phylogenomic databases

    HOGENOMiHOG000006546.
    HOVERGENiHBG000639.
    KOiK14704.
    TreeFamiTF313784.

    Enzyme and pathway databases

    SABIO-RKQ8CIW6.

    Miscellaneous databases

    PROiQ8CIW6.
    SOURCEiSearch...

    Family and domain databases

    Gene3Di3.30.750.24. 2 hits.
    InterProiIPR018045. S04_transporter_CS.
    IPR011547. SLC26A/SulP_dom.
    IPR001902. SLC26A/SulP_fam.
    IPR030323. SLC26A6.
    IPR002645. STAS_dom.
    [Graphical view]
    PANTHERiPTHR11814. PTHR11814. 2 hits.
    PTHR11814:SF113. PTHR11814:SF113. 2 hits.
    PfamiPF01740. STAS. 1 hit.
    PF00916. Sulfate_transp. 1 hit.
    [Graphical view]
    SUPFAMiSSF52091. SSF52091. 2 hits.
    TIGRFAMsiTIGR00815. sulP. 1 hit.
    PROSITEiPS01130. SLC26A. 1 hit.
    PS50801. STAS. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiS26A6_MOUSE
    AccessioniPrimary (citable) accession number: Q8CIW6
    Secondary accession number(s): E9Q4D3
    , Q3TQD3, Q812E2, Q8CJD0, Q8K142, Q923J3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 18, 2013
    Last sequence update: September 18, 2013
    Last modified: November 2, 2016
    This is version 93 of the entry and version 2 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

    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 one 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.