ID   S4A7_MOUSE              Reviewed;        1034 AA.
AC   Q8BTY2; Q3U5H7;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-FEB-2006, sequence version 2.
DT   08-NOV-2023, entry version 142.
DE   RecName: Full=Sodium bicarbonate cotransporter 3;
DE   AltName: Full=Solute carrier family 4 member 7;
GN   Name=Slc4a7; Synonyms=Nbc3;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 1-932 (ISOFORM 1).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Thymus;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 826-1034 (ISOFORM 1).
RC   STRAIN=C57BL/6J; TISSUE=Brain;
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   [3]
RP   INTERACTION WITH CFTR AND NHERF1.
RX   PubMed=12403779; DOI=10.1074/jbc.m201862200;
RA   Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A.,
RA   Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I.;
RT   "The cystic fibrosis transmembrane conductance regulator interacts with and
RT   regulates the activity of the HCO3- salvage transporter human Na+-HCO3-
RT   cotransport isoform 3.";
RL   J. Biol. Chem. 277:50503-50509(2002).
RN   [4]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=12808454; DOI=10.1038/ng1176;
RA   Bok D., Galbraith G., Lopez I., Woodruff M., Nusinowitz S.,
RA   BeltrandelRio H., Huang W., Zhao S., Geske R., Montgomery C.,
RA   van Sligtenhorst I., Friddle C., Platt K., Sparks M.J., Pushkin A.,
RA   Abuladze N., Ishiyama A., Dukkipati R., Liu W., Kurtz I.;
RT   "Blindness and auditory impairment caused by loss of the sodium bicarbonate
RT   cotransporter NBC3.";
RL   Nat. Genet. 34:313-319(2003).
RN   [5]
RP   INTERACTION WITH USH1C, AND TISSUE SPECIFICITY.
RX   PubMed=16301216; DOI=10.1093/hmg/ddi417;
RA   Reiners J., van Wijk E., Maerker T., Zimmermann U., Juergens K.,
RA   te Brinke H., Overlack N., Roepman R., Knipper M., Kremer H., Wolfrum U.;
RT   "Scaffold protein harmonin (USH1C) provides molecular links between Usher
RT   syndrome type 1 and type 2.";
RL   Hum. Mol. Genet. 14:3933-3943(2005).
RN   [6]
RP   FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=16439691; DOI=10.1161/01.res.0000204750.04971.76;
RA   Boedtkjer E., Praetorius J., Aalkjaer C.;
RT   "NBCn1 (slc4a7) mediates the Na+-dependent bicarbonate transport important
RT   for regulation of intracellular pH in mouse vascular smooth muscle cells.";
RL   Circ. Res. 98:515-523(2006).
RN   [7]
RP   REPRESSION BY HYPOXIA.
RX   PubMed=17928512; DOI=10.1152/ajpregu.00497.2007;
RA   Chen L.M., Choi I., Haddad G.G., Boron W.F.;
RT   "Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and
RT   SLC4A10 (NCBE) in mouse brain.";
RL   Am. J. Physiol. 293:R2412-R2420(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-57; SER-238 AND SER-960,
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-263 (ISOFORM 2), AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA   Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA   Thibault P.;
RT   "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL   Immunity 30:143-154(2009).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-960, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA   Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT   "Large scale localization of protein phosphorylation by use of electron
RT   capture dissociation mass spectrometry.";
RL   Mol. Cell. Proteomics 8:904-912(2009).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-654 AND ASN-664.
RX   PubMed=19349973; DOI=10.1038/nbt.1532;
RA   Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA   Schiess R., Aebersold R., Watts J.D.;
RT   "Mass-spectrometric identification and relative quantification of N-linked
RT   cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238; SER-250; SER-271;
RP   SER-275; THR-951 AND SER-960, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT
RP   SER-260 AND SER-263 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
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   [13]
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=22586225; DOI=10.1113/jphysiol.2011.226506;
RA   Chen M., Praetorius J., Zheng W., Xiao F., Riederer B., Singh A.K.,
RA   Stieger N., Wang J., Shull G.E., Aalkjaer C., Seidler U.;
RT   "The electroneutral Na(+):HCO(3)(-) cotransporter NBCn1 is a major pHi
RT   regulator in murine duodenum.";
RL   J. Physiol. (Lond.) 590:3317-3333(2012).
RN   [14]
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=23401617; DOI=10.1113/jphysiol.2012.247874;
RA   Singh A.K., Xia W., Riederer B., Juric M., Li J., Zheng W., Cinar A.,
RA   Xiao F., Bachmann O., Song P., Praetorius J., Aalkjaer C., Seidler U.;
RT   "Essential role of the electroneutral Na+-HCO3- cotransporter NBCn1 in
RT   murine duodenal acid-base balance and colonic mucus layer build-up in
RT   vivo.";
RL   J. Physiol. (Lond.) 591:2189-2204(2013).
RN   [15]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=33321164; DOI=10.1016/j.bbr.2020.113065;
RA   Choi I., Beedholm K., Dam V.S., Bae S.H., Noble D.J., Garraway S.M.,
RA   Aalkjaer C., Boedtkjer E.;
RT   "Sodium bicarbonate cotransporter NBCn1/Slc4a7 affects locomotor activity
RT   and hearing in mice.";
RL   Behav. Brain Res. 401:113065-113065(2021).
CC   -!- FUNCTION: Electroneutral sodium- and bicarbonate-dependent
CC       cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry (PubMed:16439691,
CC       PubMed:22586225, PubMed:23401617). Mediates the sodium-dependent
CC       bicarbonate transport important for pH recovery after acid load as well
CC       as for regulation of steady-state pH in the duodenum and vascular
CC       smooth muscle cells (PubMed:16439691, PubMed:22586225,
CC       PubMed:23401617). Plays a key role in macrophage acidification,
CC       mediating bicarbonate import into the cytoplasm which is crucial for
CC       net acid extrusion and maintenance of cytoplasmic pH during
CC       phagocytosis (By similarity). Provides cellular bicarbonate for de novo
CC       purine and pyrimidine synthesis and is a key mediator of de novo
CC       nucleotide synthesis downstream of mTORC1 signaling in proliferating
CC       cells (By similarity). May be involved in maintaining locomotor
CC       activity, exploratory behavior, and hearing (PubMed:12808454,
CC       PubMed:33321164). {ECO:0000250|UniProtKB:Q9Y6M7,
CC       ECO:0000269|PubMed:12808454, ECO:0000269|PubMed:16439691,
CC       ECO:0000269|PubMed:22586225, ECO:0000269|PubMed:23401617,
CC       ECO:0000269|PubMed:33321164}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=hydrogencarbonate(in) + Na(+)(in) = hydrogencarbonate(out) +
CC         Na(+)(out); Xref=Rhea:RHEA:70267, ChEBI:CHEBI:17544,
CC         ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:16439691,
CC         ECO:0000269|PubMed:22586225, ECO:0000269|PubMed:23401617};
CC   -!- ACTIVITY REGULATION: Activity is inhibited by 4,4'-di-
CC       isothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of
CC       several anion channels and transporters).
CC       {ECO:0000269|PubMed:16439691}.
CC   -!- SUBUNIT: Forms a complex with ATP6V1B1 and NHERF1/EBP50. Interacts in a
CC       pH dependent-manner with CA2/carbonic anhydrase 2 (By similarity).
CC       Interacts with CFTR through NHERF1/EBP50. Interacts with USH1C.
CC       {ECO:0000250|UniProtKB:Q9Y6M7, ECO:0000269|PubMed:12403779,
CC       ECO:0000269|PubMed:16301216}.
CC   -!- INTERACTION:
CC       Q8BTY2; Q9ES64-3: Ush1c; NbExp=2; IntAct=EBI-11621670, EBI-7418919;
CC   -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC       {ECO:0000269|PubMed:22586225, ECO:0000269|PubMed:23401617}; Multi-pass
CC       membrane protein {ECO:0000255}. Apical cell membrane
CC       {ECO:0000250|UniProtKB:Q9R1N3}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell projection, stereocilium
CC       {ECO:0000250|UniProtKB:Q9R1N3}. Cell membrane
CC       {ECO:0000269|PubMed:16439691}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localizes to the stereocilia of cochlear outer hair
CC       cells and to the lateral membrane of cochlear inner hair cells (By
CC       similarity). {ECO:0000250|UniProtKB:Q9R1N3}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8BTY2-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8BTY2-2; Sequence=VSP_017166, VSP_017167, VSP_017168;
CC   -!- TISSUE SPECIFICITY: Expressed in the spiral ligament throughout the
CC       cochlea and in photoreceptors of the outer plexiform layer of the
CC       retina (at protein level). {ECO:0000269|PubMed:12808454,
CC       ECO:0000269|PubMed:16301216}.
CC   -!- INDUCTION: Repressed in the brain by chronic continuous hypoxia (at
CC       protein level). {ECO:0000269|PubMed:17928512}.
CC   -!- DOMAIN: The PDZ-binding motif mediates interaction with the CFTR,
CC       NHERF1/EBP50 complex and probably with USH1C.
CC       {ECO:0000250|UniProtKB:Q9Y6M7}.
CC   -!- DISRUPTION PHENOTYPE: Deafness and blindness due to degeneration of
CC       sensory receptors in internal ear and retina (PubMed:12808454). Mice
CC       show impaired hearing and reduced locomotor activity and
CC       rearing/grooming behaviors (PubMed:33321164). Show defects in the
CC       mucosal protective responses to luminal acid, both in the pH recovery
CC       of enterocytes after luminal acid exposure and in the acid-induced
CC       HCO3(-) secretory defect in the duodenum (PubMed:22586225,
CC       PubMed:23401617). Knockdown in mesenteric small arteries leads to a
CC       dramatic decrease in the Na(+)-dependent base influx and in steady-
CC       state pH (PubMed:16439691). {ECO:0000269|PubMed:12808454,
CC       ECO:0000269|PubMed:16439691, ECO:0000269|PubMed:22586225,
CC       ECO:0000269|PubMed:23401617, ECO:0000269|PubMed:33321164}.
CC   -!- SIMILARITY: Belongs to the anion exchanger (TC 2.A.31) family.
CC       {ECO:0000305}.
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DR   EMBL; AK088400; BAC40330.1; -; mRNA.
DR   EMBL; AK152233; BAE31059.1; -; mRNA.
DR   EMBL; AK153567; BAE32101.1; -; mRNA.
DR   EMBL; CN532915; -; NOT_ANNOTATED_CDS; mRNA.
DR   AlphaFoldDB; Q8BTY2; -.
DR   SMR; Q8BTY2; -.
DR   IntAct; Q8BTY2; 1.
DR   STRING; 10090.ENSMUSP00000058313; -.
DR   ChEMBL; CHEMBL3774291; -.
DR   GlyCosmos; Q8BTY2; 5 sites, No reported glycans.
DR   GlyGen; Q8BTY2; 5 sites.
DR   iPTMnet; Q8BTY2; -.
DR   PhosphoSitePlus; Q8BTY2; -.
DR   SwissPalm; Q8BTY2; -.
DR   EPD; Q8BTY2; -.
DR   jPOST; Q8BTY2; -.
DR   MaxQB; Q8BTY2; -.
DR   PaxDb; 10090-ENSMUSP00000058313; -.
DR   PeptideAtlas; Q8BTY2; -.
DR   ProteomicsDB; 260797; -. [Q8BTY2-1]
DR   ProteomicsDB; 260798; -. [Q8BTY2-2]
DR   Pumba; Q8BTY2; -.
DR   AGR; MGI:2443878; -.
DR   MGI; MGI:2443878; Slc4a7.
DR   eggNOG; KOG1172; Eukaryota.
DR   InParanoid; Q8BTY2; -.
DR   PhylomeDB; Q8BTY2; -.
DR   Reactome; R-MMU-425381; Bicarbonate transporters.
DR   Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR   Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR   Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR   Reactome; R-MMU-9035034; RHOF GTPase cycle.
DR   ChiTaRS; Slc4a7; mouse.
DR   PRO; PR:Q8BTY2; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8BTY2; Protein.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0032420; C:stereocilium; ISO:MGI.
DR   GO; GO:0008509; F:monoatomic anion transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0008510; F:sodium:bicarbonate symporter activity; IMP:UniProtKB.
DR   GO; GO:0005452; F:solute:inorganic anion antiporter activity; IEA:InterPro.
DR   GO; GO:0060117; P:auditory receptor cell development; IMP:MGI.
DR   GO; GO:0015701; P:bicarbonate transport; IBA:GO_Central.
DR   GO; GO:0060219; P:camera-type eye photoreceptor cell differentiation; IMP:MGI.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI.
DR   GO; GO:0021747; P:cochlear nucleus development; IMP:MGI.
DR   GO; GO:0035641; P:locomotory exploration behavior; IMP:UniProtKB.
DR   GO; GO:0090383; P:phagosome acidification; ISO:MGI.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; ISO:MGI.
DR   GO; GO:0006221; P:pyrimidine nucleotide biosynthetic process; ISO:MGI.
DR   GO; GO:0051453; P:regulation of intracellular pH; IMP:UniProtKB.
DR   GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IMP:MGI.
DR   GO; GO:0046666; P:retinal cell programmed cell death; IMP:MGI.
DR   GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR   GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR   GO; GO:0007601; P:visual perception; IMP:MGI.
DR   Gene3D; 1.10.287.570; Helical hairpin bin; 1.
DR   InterPro; IPR013769; Band3_cytoplasmic_dom.
DR   InterPro; IPR011531; HCO3_transpt-like_TM_dom.
DR   InterPro; IPR003020; HCO3_transpt_euk.
DR   InterPro; IPR003024; Na/HCO3_transpt.
DR   InterPro; IPR016152; PTrfase/Anion_transptr.
DR   NCBIfam; TIGR00834; ae; 1.
DR   PANTHER; PTHR11453; ANION EXCHANGE PROTEIN; 1.
DR   PANTHER; PTHR11453:SF105; SODIUM BICARBONATE COTRANSPORTER 3; 1.
DR   Pfam; PF07565; Band_3_cyto; 1.
DR   Pfam; PF00955; HCO3_cotransp; 1.
DR   PRINTS; PR01231; HCO3TRNSPORT.
DR   PRINTS; PR01232; NAHCO3TRSPRT.
DR   SUPFAM; SSF55804; Phoshotransferase/anion transport protein; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cell projection; Disulfide bond;
KW   Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW   Sodium; Sodium transport; Symport; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..1034
FT                   /note="Sodium bicarbonate cotransporter 3"
FT                   /id="PRO_0000079234"
FT   TOPO_DOM        1..476
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        477..497
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        498..505
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        506..526
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        527..563
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        564..584
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        585..593
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        594..614
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        615..685
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        686..706
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        707..729
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        730..750
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        751..776
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        777..797
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        798..812
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        813..833
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        834..876
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        877..897
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        898..1034
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          53..99
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          250..276
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          815..915
FT                   /note="Essential for cell membrane localization and
FT                   transport activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6M7"
FT   REGION          918..920
FT                   /note="CA2-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          926..946
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           1031..1034
FT                   /note="PDZ-binding"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        58..77
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         57
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319"
FT   MOD_RES         60
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6M7"
FT   MOD_RES         89
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R1N3"
FT   MOD_RES         155
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R1N3"
FT   MOD_RES         238
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         250
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         268
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9R1N3"
FT   MOD_RES         271
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         275
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17242355,
FT                   ECO:0007744|PubMed:21183079"
FT   MOD_RES         424
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6M7"
FT   MOD_RES         951
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         960
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19131326,
FT                   ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT   MOD_RES         1033
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6M7"
FT   CARBOHYD        176
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        644
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        654
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973"
FT   CARBOHYD        664
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19349973"
FT   DISULFID        634..636
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   DISULFID        670..682
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y6R1"
FT   VAR_SEQ         243
FT                   /note="G -> GKKHSDPHLLERNG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_017166"
FT   VAR_SEQ         815
FT                   /note="F -> KGAGYHLDLLMVGVMLGVCSIMGLPWFVAATVLSISHVNSLKVESEC
FT                   SAPGEQPKFLGIREQRVTGLMIFILMGLSVFMTSVLKVKPLWQCSTILFTLTFILSCKE
FT                   IKH (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_017167"
FT   VAR_SEQ         816..1034
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_017168"
FT   CONFLICT        430
FT                   /note="G -> D (in Ref. 1; BAC40330)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        717
FT                   /note="G -> R (in Ref. 1; BAC40330)"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         Q8BTY2-2:260
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         Q8BTY2-2:263
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19144319,
FT                   ECO:0007744|PubMed:21183079"
SQ   SEQUENCE   1034 AA;  116514 MW;  92B080274D206097 CRC64;
     MEADGAGEQM RPLLTRGPDE EAVVDLGKTS STVNTKFEKE ELESHRAVYV GVHVPFSKES
     RRRHKHRGHK HHHRRRKDKD SDKEDGRESP SYDTPSQRVQ FILGTEDDDE EHIPHDLFTE
     MDELCYRDGE EYEWKETARW LKFEEDVEDG GDRWSKPYVA TLSLHSLFEL RSCILNGTVM
     LDMRASTLDE IADMVLDNMI ASGQLDDSIR ENVREALLKR HHHQNEKRFT SRIPLVRSFA
     DIGILASPQS APGNLDNSKS GEMKGNGSGG SRENSTVDFS KVDMNFMRKI PTGAEASNVL
     VGEVDFLERP IIAFVRLAPA VLLSGLTEVP VPTRFLFLLL GPAGKAPQYH EIGRSIATLM
     TDEIFHDVAY KAKDRNDLLS GIDEFLDQVT VLPPGEWDPS IRIEPPKSVP SQEKRKIPVF
     PNGSAAMSVG PPKEDDHHAG PELQRTGRLF GGLILDIKRK APFFLSDFKD ALSLQCLASI
     LFLYCACMSP VITFGGLLGE ATEGRISAIE SLFGASLTGI AYSLFAGQPL TILGSTGPVL
     VFEKILFKFC RDYHLSYLSL RTSIGLWTSF LCIVLVATDA SSLVCYITRF TEEAFAALIC
     IIFIYEALEK LFHLGEIYAF NMHNNLDELT SYTCVCAEPS NPSNETLELW KRKNITAYSV
     SWGNLTVSEC KTFHGMFVGS ACGPHGPYVP DVLFWCVVLF FTTFFLSSFL KQFKTKGYFP
     TKVRSTISDF AVFLTIVIMV AIDYLVGIPS PKLHVPEKFE PTDPSRGWII SPLGDNPWWT
     LLIAAVPALL CTILIFMDQQ ITAVIINRKE HKLKFIPMPV LYGVFLYMGV SSLKGIQFFD
     RIKLFGMPAK HQPDLIYLRY VPLWKVHVFT VVQLTCLVLL WVIKASAAAV VFPMMVLALV
     FVRKLMDLCF TKRELSWLDD LMPESKKKKE DDKKKKEKEE AERMLQDDED TVHLPFERGS
     LLQIPVKTLK YSIDPSVVNI SDEMAKTAQW KALSMNTENA KVTRPNTSPE KPVSVTINFE
     DEPSKKYMDA ETSL
//