S26A6_MOUSE
ID S26A6_MOUSE Reviewed; 758 AA.
AC Q8CIW6; E9Q4D3; Q3TQD3; Q812E2; Q8CJD0; Q8K142; Q923J3;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Solute carrier family 26 member 6;
DE AltName: Full=Anion exchange transporter;
DE AltName: Full=Chloride-formate exchanger;
DE AltName: Full=Pendrin-L1;
DE AltName: Full=Pendrin-like protein 1;
DE AltName: Full=Putative anion transporter-1;
DE Short=Pat-1;
GN Name=Slc26a6 {ECO:0000312|MGI:MGI:2159728}; Synonyms=Cfex, Pat1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=11459928; DOI=10.1073/pnas.141241098;
RA Knauf F., Yang C.L., Thomson R.B., Mentone S.A., Giebisch G., Aronson P.S.;
RT "Identification of a chloride-formate exchanger expressed on the brush
RT border membrane of renal proximal tubule cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9425-9430(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=12217875; DOI=10.1152/ajprenal.00079.2002;
RA Xie Q., Welch R., Mercado A., Romero M.F., Mount D.B.;
RT "Molecular characterization of the murine Slc26a6 anion exchanger:
RT functional comparison with Slc26a1.";
RL Am. J. Physiol. 283:F826-F838(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=BALB/cJ; TISSUE=Kidney;
RX PubMed=15203903; DOI=10.1080/10611860410001693742;
RA Nozawa T., Sugiura S., Hashino Y., Tsuji A., Tamai I.;
RT "Role of anion exchange transporter PAT1 (SLC26A6) in intestinal absorption
RT of organic anions.";
RL J. Drug. Target. 12:97-104(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11842009; DOI=10.1152/ajpgi.00338.2001;
RA Wang Z., Petrovic S., Mann E., Soleimani M.;
RT "Identification of an apical Cl(-)/HCO3(-) exchanger in the small
RT intestine.";
RL Am. J. Physiol. 282:G573-G579(2002).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12119287; DOI=10.1074/jbc.m202660200;
RA Jiang Z., Grichtchenko I.I., Boron W.F., Aronson P.S.;
RT "Specificity of anion exchange mediated by mouse Slc26a6.";
RL J. Biol. Chem. 277:33963-33967(2002).
RN [10]
RP FUNCTION, INTERACTION WITH PDZK1, AND SUBCELLULAR LOCATION.
RX PubMed=16141316; DOI=10.1073/pnas.0506578102;
RA Thomson R.B., Wang T., Thomson B.R., Tarrats L., Girardi A., Mentone S.,
RA Soleimani M., Kocher O., Aronson P.S.;
RT "Role of PDZK1 in membrane expression of renal brush border ion
RT exchangers.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13331-13336(2005).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17053783; DOI=10.1038/sj.emboj.7601387;
RA Wang Y., Soyombo A.A., Shcheynikov N., Zeng W., Dorwart M., Marino C.R.,
RA Thomas P.J., Muallem S.;
RT "Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3-
RT secretion: relevance to cystic fibrosis.";
RL EMBO J. 25:5049-5057(2006).
RN [12]
RP FUNCTION.
RX PubMed=16606687; DOI=10.1085/jgp.200509392;
RA Shcheynikov N., Wang Y., Park M., Ko S.B., Dorwart M., Naruse S.,
RA Thomas P.J., Muallem S.;
RT "Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and
RT slc26a6.";
RL J. Gen. Physiol. 127:511-524(2006).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16532010; DOI=10.1038/ng1762;
RA Jiang Z., Asplin J.R., Evan A.P., Rajendran V.M., Velazquez H.,
RA Nottoli T.P., Binder H.J., Aronson P.S.;
RT "Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.";
RL Nat. Genet. 38:474-478(2006).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17170027; DOI=10.1152/ajpgi.00354.2006;
RA Simpson J.E., Schweinfest C.W., Shull G.E., Gawenis L.R., Walker N.M.,
RA Boyle K.T., Soleimani M., Clarke L.L.;
RT "PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3-exchanger in
RT the upper villous epithelium of the murine duodenum.";
RL Am. J. Physiol. 292:G1079-G1088(2007).
RN [15]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-575.
RX PubMed=17151144; DOI=10.1152/ajpcell.00447.2006;
RA Hassan H.A., Mentone S., Karniski L.P., Rajendran V.M., Aronson P.S.;
RT "Regulation of anion exchanger Slc26a6 by protein kinase C.";
RL Am. J. Physiol. 292:C1485-C1492(2007).
RN [16]
RP FUNCTION.
RX PubMed=18046080; DOI=10.1159/000111826;
RA Petrovic S., Barone S., Wang Z., McDonough A.A., Amlal H., Soleimani M.;
RT "Slc26a6 (PAT1) deletion downregulates the apical Na+/H+ exchanger in the
RT straight segment of the proximal tubule.";
RL Am. J. Nephrol. 28:330-338(2008).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18496516; DOI=10.1038/ki.2008.184;
RA Singh A.K., Amlal H., Haas P.J., Dringenberg U., Fussell S., Barone S.L.,
RA Engelhardt R., Zuo J., Seidler U., Soleimani M.;
RT "Fructose-induced hypertension: essential role of chloride and fructose
RT absorbing transporters PAT1 and Glut5.";
RL Kidney Int. 74:438-447(2008).
RN [18]
RP FUNCTION.
RX PubMed=20150244; DOI=10.1152/ajpgi.00293.2009;
RA Simpson J.E., Walker N.M., Supuran C.T., Soleimani M., Clarke L.L.;
RT "Putative anion transporter-1 (Pat-1, Slc26a6) contributes to intracellular
RT pH regulation during H+-dipeptide transport in duodenal villous
RT epithelium.";
RL Am. J. Physiol. 298:G683-G691(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP FUNCTION.
RX PubMed=20969732; DOI=10.1111/j.1748-1716.2010.02210.x;
RA Walker N.M., Simpson J.E., Hoover E.E., Brazill J.M., Schweinfest C.W.,
RA Soleimani M., Clarke L.L.;
RT "Functional activity of Pat-1 (Slc26a6) Cl(-)/HCO(3)(-) exchange in the
RT lower villus epithelium of murine duodenum.";
RL Acta Physiol. 201:21-31(2011).
RN [21]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=22021714; DOI=10.1681/asn.2011040433;
RA Knauf F., Ko N., Jiang Z., Robertson W.G., Van Itallie C.M., Anderson J.M.,
RA Aronson P.S.;
RT "Net intestinal transport of oxalate reflects passive absorption and
RT SLC26A6-mediated secretion.";
RL J. Am. Soc. Nephrol. 22:2247-2255(2011).
RN [22]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=22895259; DOI=10.1152/ajpcell.00151.2012;
RA Song Y., Yamamoto A., Steward M.C., Ko S.B., Stewart A.K., Soleimani M.,
RA Liu B.C., Kondo T., Jin C.X., Ishiguro H.;
RT "Deletion of Slc26a6 alters the stoichiometry of apical Cl-/HCO-3 exchange
RT in mouse pancreatic duct.";
RL Am. J. Physiol. 303:C815-C824(2012).
RN [23]
RP FUNCTION, INTERACTION WITH CFTR; SLC26A3 AND SLC9A3R1, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21976599; DOI=10.1095/biolreprod.111.094037;
RA Chavez J.C., Hernandez-Gonzalez E.O., Wertheimer E., Visconti P.E.,
RA Darszon A., Trevino C.L.;
RT "Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the
RT Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm
RT capacitation.";
RL Biol. Reprod. 86:1-14(2012).
RN [24]
RP INTERACTION WITH AHCYL1.
RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047;
RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H.,
RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K.,
RA Muallem S.;
RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
RT epithelial transport in mice.";
RL Gastroenterology 145:232-241(2013).
CC -!- FUNCTION: Apical membrane anion-exchanger with wide epithelial
CC distribution that plays a role as a component of the pH buffering
CC system for maintaining acid-base homeostasis. Acts as a versatile DIDS-
CC sensitive inorganic and organic anion transporter that mediates the
CC uptake of monovalent anions like chloride, bicarbonate, formate and
CC hydroxyl ion and divalent anions like sulfate and oxalate. Functions in
CC multiple exchange modes involving pairs of these anions, which include
CC chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-
CC sulfate and chloride-formate exchange. Apical membrane chloride-
CC bicarbonate exchanger that mediates luminal chloride absorption and
CC bicarbonate secretion by the small intestinal brush border membrane and
CC contributes to intracellular pH regulation in the duodenal upper
CC villous epithelium during proton-coupled peptide absorption, possibly
CC by providing a bicarbonate import pathway. Its association with
CC carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence
CC maximizes the local concentration of bicarbonate at the transporter
CC site. Mediates also intestinal chloride absorption and oxalate
CC secretion, thereby preventing hyperoxaluria and calcium oxalate
CC urolithiasis. Transepithelial oxalate secretion, chloride-formate,
CC chloride-oxalate and chloride-bicarbonate transport activities in the
CC duodenum are inhibited by PKC activation in a calcium-independent
CC manner. The apical membrane chloride-bicarbonate exchanger provides
CC also a major route for fluid and bicarbonate secretion into the
CC proximal tubules of the kidney as well as into the proximal part of the
CC interlobular pancreatic ductal tree, where it mediates electrogenic
CC chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry
CC of 1:2, and hence will dilute and alkalinize protein-rich acinar
CC secretion. Mediates also the transcellular sulfate absorption and
CC oxalate secretion across the apical membrane in the duodenum and the
CC formate ion efflux at the apical brush border of cells in the proximal
CC tubules of kidney. Plays a role in sperm capacitation by increasing
CC intracellular pH. {ECO:0000269|PubMed:11459928,
CC ECO:0000269|PubMed:11842009, ECO:0000269|PubMed:12119287,
CC ECO:0000269|PubMed:12217875, ECO:0000269|PubMed:15203903,
CC ECO:0000269|PubMed:16141316, ECO:0000269|PubMed:16532010,
CC ECO:0000269|PubMed:16606687, ECO:0000269|PubMed:17053783,
CC ECO:0000269|PubMed:17170027, ECO:0000269|PubMed:18046080,
CC ECO:0000269|PubMed:18496516, ECO:0000269|PubMed:20150244,
CC ECO:0000269|PubMed:20969732, ECO:0000269|PubMed:21976599,
CC ECO:0000269|PubMed:22021714, ECO:0000269|PubMed:22895259}.
CC -!- ACTIVITY REGULATION: Apical membrane chloride-bicarbonate exchange
CC activity of the pancreatic duct is inhibited by DIDS (By similarity).
CC Apical membrane chloride-formate exchange activity in the proximal
CC tubules of the kidney and oxalate secretion in the duodenum are
CC inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS
CC - an inhibitor of several anion channels and transporters).
CC {ECO:0000250, ECO:0000269|PubMed:11459928, ECO:0000269|PubMed:12119287,
CC ECO:0000269|PubMed:12217875, ECO:0000269|PubMed:15203903,
CC ECO:0000269|PubMed:22021714, ECO:0000269|PubMed:22895259}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 mM for oxalate {ECO:0000269|PubMed:12119287};
CC KM=0.314 mM for oxalate {ECO:0000269|PubMed:15203903};
CC KM=3.87 mM for formate {ECO:0000269|PubMed:15203903};
CC -!- SUBUNIT: Interacts (via C-terminal cytoplasmic domain) with CA2; the
CC interaction stimulates chloride-bicarbonate exchange activity.
CC Interacts with SLC9A3R1 (via the PDZ domains). Interacts with SLC9A3R2
CC (via the PDZ domains) (By similarity). Interacts (via C-terminal
CC domain) with PDZK1 (via C-terminal PDZ domain); the interaction induces
CC chloride and oxalate exchange transport. Interacts with CFTR, SLC26A3
CC and SLC9A3R1. Interacts with AHCYL1; the interaction increases SLC26A6
CC activity (PubMed:23542070). {ECO:0000250|UniProtKB:Q9BXS9,
CC ECO:0000269|PubMed:16141316, ECO:0000269|PubMed:21976599,
CC ECO:0000269|PubMed:23542070}.
CC -!- INTERACTION:
CC Q8CIW6; P26361: Cftr; NbExp=3; IntAct=EBI-6895517, EBI-6115317;
CC Q8CIW6; Q9WVC8: Slc26a3; NbExp=2; IntAct=EBI-6895517, EBI-6895537;
CC Q8CIW6; P70441: Slc9a3r1; NbExp=2; IntAct=EBI-6895517, EBI-1184085;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC membrane; Multi-pass membrane protein. Apical cell membrane; Multi-pass
CC membrane protein. Cytoplasmic vesicle membrane; Multi-pass membrane
CC protein. Microsome. Note=Colocalized with CA2 at the surface of the
CC cell membrane in order to form a bicarbonate transport metabolon;
CC colocalization is reduced in phorbol myristate acetate (PMA)-induced
CC cells (By similarity). Localized in sperm membranes. Colocalizes with
CC CFTR at the midpiece of sperm tail. Localizes to the apical membrane
CC brush border of epithelial cells in the proximal tubules of kidney, of
CC enterocytes of the small intestine and of gastric parietal cells in the
CC stomach. May be translocated from the cytosolic surface of the cell
CC membrane to the intracellular space by PKC in phorbol myristate acetate
CC (PMA)-induced cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Slc26a6a;
CC IsoId=Q8CIW6-1; Sequence=Displayed;
CC Name=2; Synonyms=Slc26a6b;
CC IsoId=Q8CIW6-2; Sequence=VSP_047853;
CC Name=3;
CC IsoId=Q8CIW6-3; Sequence=VSP_047853, VSP_047854;
CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level). Highly
CC expressed in stomach, kidney, heart and small intestine, low in the
CC lung, liver, testis, brain, skeletal muscle and colon. Expressed in
CC spermatogenic cells. Isoform 1 is expressed in intestine, kidney,
CC testis, brain, muscle, heart, and stomach.
CC {ECO:0000269|PubMed:11459928, ECO:0000269|PubMed:11842009,
CC ECO:0000269|PubMed:12217875, ECO:0000269|PubMed:17170027,
CC ECO:0000269|PubMed:21976599}.
CC -!- INDUCTION: Up-regulated by dietary fructose intake (at protein level).
CC {ECO:0000269|PubMed:18496516}.
CC -!- PTM: Phosphorylated on serine residues by PKC; the phosphorylation
CC disrupts interaction with carbonic anhydrase CA2 and reduces
CC bicarbonate transport activity in a phorbol myristate acetate (PMA)-
CC induced manner. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice show an important decrease in salt
CC absorption in the intestine and failed to develop hypertension on a
CC high-fructose diet. Show a reduction in pancreatic duct fluid and
CC bicarbonate secretion. Show enhanced oxalate absorption in the
CC intestine leading to hyperoxalemia and hyperoxaluria with high
CC incidence of calcium-oxalate stones formation.
CC {ECO:0000269|PubMed:16532010, ECO:0000269|PubMed:17053783,
CC ECO:0000269|PubMed:18496516}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AC168054; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAAA01111125; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAAA01200220; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY032863; AAK51131.1; -; mRNA.
DR EMBL; AF248494; AAN07089.1; -; mRNA.
DR EMBL; AY049076; AAL13129.1; -; mRNA.
DR EMBL; AB099881; BAC55182.1; -; mRNA.
DR EMBL; AK163670; BAE37450.1; -; mRNA.
DR EMBL; AK163671; BAE37451.1; -; mRNA.
DR EMBL; AC168054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01111125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CAAA01200220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466560; EDL21319.1; -; Genomic_DNA.
DR EMBL; BC028856; AAH28856.1; -; mRNA.
DR RefSeq; NP_599252.2; NM_134420.4. [Q8CIW6-2]
DR AlphaFoldDB; Q8CIW6; -.
DR SMR; Q8CIW6; -.
DR IntAct; Q8CIW6; 3.
DR STRING; 10090.ENSMUSP00000095979; -.
DR ChEMBL; CHEMBL4523388; -.
DR TCDB; 2.A.53.2.8; the sulfate permease (sulp) family.
DR iPTMnet; Q8CIW6; -.
DR PhosphoSitePlus; Q8CIW6; -.
DR SwissPalm; Q8CIW6; -.
DR PeptideAtlas; Q8CIW6; -.
DR PRIDE; Q8CIW6; -.
DR ProteomicsDB; 260896; -. [Q8CIW6-1]
DR ProteomicsDB; 260897; -. [Q8CIW6-2]
DR ProteomicsDB; 260898; -. [Q8CIW6-3]
DR Antibodypedia; 30187; 206 antibodies from 26 providers.
DR DNASU; 171429; -.
DR Ensembl; ENSMUST00000188557; ENSMUSP00000140849; ENSMUSG00000023259. [Q8CIW6-1]
DR Ensembl; ENSMUST00000239562; ENSMUSP00000159445; ENSMUSG00000023259. [Q8CIW6-2]
DR GeneID; 171429; -.
DR KEGG; mmu:171429; -.
DR UCSC; uc009rrd.1; mouse. [Q8CIW6-1]
DR CTD; 65010; -.
DR MGI; MGI:2159728; Slc26a6.
DR eggNOG; KOG0236; Eukaryota.
DR GeneTree; ENSGT01050000244807; -.
DR OMA; PNCVLAS; -.
DR OrthoDB; 690428at2759; -.
DR TreeFam; TF313784; -.
DR Reactome; R-MMU-427601; Multifunctional anion exchangers.
DR SABIO-RK; Q8CIW6; -.
DR BioGRID-ORCS; 171429; 1 hit in 22 CRISPR screens.
DR PRO; PR:Q8CIW6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8CIW6; protein.
DR Bgee; ENSMUSG00000023259; Expressed in duodenum and 62 other tissues.
DR ExpressionAtlas; Q8CIW6; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; IDA:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; IDA:UniProtKB.
DR GO; GO:0015301; F:anion:anion antiporter activity; IDA:UniProtKB.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015562; F:efflux transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015660; F:formate efflux transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0015499; F:formate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019531; F:oxalate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
DR GO; GO:0008271; F:secondary active sulfate transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015116; F:sulfate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:UniProtKB.
DR GO; GO:0015701; P:bicarbonate transport; IDA:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0071332; P:cellular response to fructose stimulus; IDA:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:MGI.
DR GO; GO:0006821; P:chloride transport; IDA:UniProtKB.
DR GO; GO:0042045; P:epithelial fluid transport; IMP:UniProtKB.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0015724; P:formate transport; IDA:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; IMP:UniProtKB.
DR GO; GO:0051454; P:intracellular pH elevation; IMP:UniProtKB.
DR GO; GO:0015797; P:mannitol transmembrane transport; IMP:UniProtKB.
DR GO; GO:0019532; P:oxalate transport; IDA:UniProtKB.
DR GO; GO:0046724; P:oxalic acid secretion; IMP:UniProtKB.
DR GO; GO:2001150; P:positive regulation of dipeptide transmembrane transport; IMP:UniProtKB.
DR GO; GO:0070528; P:protein kinase C signaling; IDA:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; IMP:UniProtKB.
DR GO; GO:0048240; P:sperm capacitation; IMP:UniProtKB.
DR GO; GO:0008272; P:sulfate transport; IDA:UniProtKB.
DR GO; GO:0030321; P:transepithelial chloride transport; IDA:UniProtKB.
DR GO; GO:0070633; P:transepithelial transport; IMP:UniProtKB.
DR Gene3D; 3.30.750.24; -; 1.
DR InterPro; IPR018045; S04_transporter_CS.
DR InterPro; IPR011547; SLC26A/SulP_dom.
DR InterPro; IPR001902; SLC26A/SulP_fam.
DR InterPro; IPR030323; SLC26A6.
DR InterPro; IPR002645; STAS_dom.
DR InterPro; IPR036513; STAS_dom_sf.
DR PANTHER; PTHR11814; PTHR11814; 1.
DR PANTHER; PTHR11814:SF113; PTHR11814:SF113; 1.
DR Pfam; PF01740; STAS; 1.
DR Pfam; PF00916; Sulfate_transp; 1.
DR SUPFAM; SSF52091; SSF52091; 1.
DR TIGRFAMs; TIGR00815; sulP; 1.
DR PROSITE; PS01130; SLC26A; 1.
DR PROSITE; PS50801; STAS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Anion exchange; Antiport; Cell membrane; Chloride;
KW Chloride channel; Cytoplasmic vesicle; Endoplasmic reticulum; Ion channel;
KW Ion transport; Membrane; Microsome; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..758
FT /note="Solute carrier family 26 member 6"
FT /id="PRO_0000423423"
FT TOPO_DOM 1..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..187
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..292
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 314..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..380
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 381..401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 402..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..485
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..506
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 507..758
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 531..741
FT /note="STAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00198"
FT REGION 585..608
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 603
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q9BXS9"
FT MOD_RES 751
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXS9"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11459928,
FT ECO:0000303|PubMed:12217875, ECO:0000303|PubMed:15203903,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT /id="VSP_047853"
FT VAR_SEQ 691..758
FT /note="IFRDFREIEVEVYIAACYSPVVAQLEAGHFFDESITKQHVFASVHDAVTFAL
FT SHRKSVPKSPVLATKL -> VRDCRQARAPQAFMLILPLASHLLATPPPNKPSPLSSPT
FT KPCPIAASLRPALFVAADFP (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_047854"
FT MUTAGEN 575
FT /note="T->A: Does not inhibit formate transport in PMA-
FT induced cells."
FT /evidence="ECO:0000269|PubMed:17151144"
FT CONFLICT 25
FT /note="E -> G (in Ref. 1; AAK51131 and 3; BAC55182)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="R -> P (in Ref. 2; AAL13129/AAN07089)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 758 AA; 82834 MW; 1512CC3A417D037B CRC64;
MGLPDGSDQG THQTQALLSA AQEMELQRRD YHVERPLLNQ EQLEDLGHWG PAAKTHQWRT
WFRCSRARAH SLLLQHVPVL GWLPRYPVRE WLLGDLLSGL SVAIMQLPQG LAYALLAGLP
PMFGLYSSFY PVFIYFLFGT SRHISVGTFA VMSVMVGSVT ESLTADKAFV QGLNATADDA
RVQVAYTLSF LVGLFQVGLG LVHFGFVVTY LSEPLVRSYT TAASVQVLVS QLKYVFGIKL
SSHSGPLSVI YTVLEVCAQL PETVPGTVVT AIVAGVALVL VKLLNEKLHR RLPLPIPGEL
LTLIGATGIS YGVKLNDRFK VDVVGNITTG LIPPVAPKTE LFATLVGNAF AIAVVGFAIA
ISLGKIFALR HGYRVDSNQE LVALGLSNLI GGFFQCFPVS CSMSRSLVQE STGGNTQVAG
AVSSLFILLI IVKLGELFRD LPKAVLAAVI IVNLKGMMKQ FSDICSLWKA NRVDLLIWLV
TFVATILLNL DIGLAVSIVF SLLLVVVRMQ LPHYSVLGQV PDTDIYRDVA EYSGAKEVPG
VKVFRSSATL YFANAELYSD SLKEKCGVDV DRLITQKKKR IKKQEMKLKR MKKAKKSQKQ
DASSKISSVS VNVNTNLEDV KSNDVEGSEA KVHQGEELQD VVSSNQEDAK APTMTSLKSL
GLPQPGFHSL ILDLSTLSFV DTVCIKSLKN IFRDFREIEV EVYIAACYSP VVAQLEAGHF
FDESITKQHV FASVHDAVTF ALSHRKSVPK SPVLATKL
