ID   SC5A1_MOUSE             Reviewed;         665 AA.
AC   Q8C3K6;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 135.
DE   RecName: Full=Sodium/glucose cotransporter 1;
DE            Short=Na(+)/glucose cotransporter 1;
DE   AltName: Full=High affinity sodium-glucose cotransporter;
DE   AltName: Full=Solute carrier family 5 member 1;
GN   Name=Slc5a1;
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].
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-585 AND THR-588, AND
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   [3]
RP   FUNCTION, TRANSPORTER ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=22124465; DOI=10.2337/db11-1029;
RA   Gorboulev V., Schuermann A., Vallon V., Kipp H., Jaschke A., Klessen D.,
RA   Friedrich A., Scherneck S., Rieg T., Cunard R., Veyhl-Wichmann M.,
RA   Srinivasan A., Balen D., Breljak D., Rexhepaj R., Parker H.E.,
RA   Gribble F.M., Reimann F., Lang F., Wiese S., Sabolic I., Sendtner M.,
RA   Koepsell H.;
RT   "Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose
RT   absorption and glucose-dependent incretin secretion.";
RL   Diabetes 61:187-196(2012).
RN   [4]
RP   FUNCTION, TRANSPORTER ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=28974690; DOI=10.1038/s41598-017-11674-3;
RA   Salker M.S., Singh Y., Zeng N., Chen H., Zhang S., Umbach A.T., Fakhri H.,
RA   Kohlhofer U., Quintanilla-Martinez L., Durairaj R.R.P., Barros F.S.V.,
RA   Vrljicak P., Ott S., Brucker S.Y., Wallwiener D., Vrhovac Madunic I.,
RA   Breljak D., Sabolic I., Koepsell H., Brosens J.J., Lang F.;
RT   "Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to
RT   Embryo Survival and Fetal Growth in Pregnancy.";
RL   Sci. Rep. 7:12612-12612(2017).
CC   -!- FUNCTION: Electrogenic Na(+)-coupled sugar simporter that actively
CC       transports D-glucose or D-galactose at the plasma membrane, with a
CC       Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by
CC       a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+)
CC       pump (PubMed:22124465, PubMed:28974690). Has a primary role in the
CC       transport of dietary monosaccharides from enterocytes to blood.
CC       Responsible for the absorption of D-glucose or D-galactose across the
CC       apical brush-border membrane of enterocytes, whereas basolateral exit
CC       is provided by GLUT2. Additionally, functions as a D-glucose sensor in
CC       enteroendocrine cells, triggering the secretion of the incretins GCG
CC       and GIP that control food intake and energy homeostasis
CC       (PubMed:22124465). Together with SGLT2, functions in reabsorption of D-
CC       glucose from glomerular filtrate, playing a nonredundant role in the S3
CC       segment of the proximal tubules (PubMed:22124465). Transports D-glucose
CC       into endometrial epithelial cells, controlling glycogen synthesis and
CC       nutritional support for the embryo as well as the decidual
CC       transformation of endometrium prior to conception (PubMed:28974690).
CC       Acts as a water channel enabling passive water transport in response to
CC       the osmotic gradient created upon sugar and Na(+) uptake. Has high
CC       water conductivity comparable to aquaporins and therefore is expected
CC       to play an important role in transepithelial water permeability,
CC       especially in the small intestine. {ECO:0000250|UniProtKB:P13866,
CC       ECO:0000269|PubMed:22124465, ECO:0000269|PubMed:28974690}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose(out) + 2 Na(+)(out) = D-glucose(in) + 2 Na(+)(in);
CC         Xref=Rhea:RHEA:70495, ChEBI:CHEBI:4167, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000269|PubMed:22124465, ECO:0000269|PubMed:28974690};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70496;
CC         Evidence={ECO:0000305|PubMed:22124465, ECO:0000305|PubMed:28974690};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-galactose(out) + 2 Na(+)(out) = D-galactose(in) + 2
CC         Na(+)(in); Xref=Rhea:RHEA:70499, ChEBI:CHEBI:4139, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000250|UniProtKB:P13866};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70500;
CC         Evidence={ECO:0000250|UniProtKB:P13866};
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:22124465, ECO:0000269|PubMed:28974690}; Multi-pass
CC       membrane protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in enterocytes and enteroendocrine cells
CC       of small intestine (at protein level) (PubMed:22124465). Expressed in
CC       S3 segments of renal proximal tubules (at protein level)
CC       (PubMed:22124465). Expressed in endometrial glandular and epithelial
CC       cells (at protein level) (PubMed:28974690).
CC       {ECO:0000269|PubMed:22124465, ECO:0000269|PubMed:28974690}.
CC   -!- DOMAIN: The cholesterol-binding site is formed by transmembrane helices
CC       TM1, TM7 and TM13. {ECO:0000250|UniProtKB:P13866}.
CC   -!- PTM: N-glycosylation is not necessary for the cotransporter function.
CC       {ECO:0000250|UniProtKB:P13866}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice had significantly lower embryo
CC       implantation rate associated with lower litter size (PubMed:28974690).
CC       On a standard diet, they developed symptoms of the glucose and
CC       galactose malabsorption and died within 2 days after weaning, a
CC       phenotype reminiscent of GGM syndrome in humans (PubMed:22124465).
CC       Weaned mice survived and were fertile when maintained on a glucose and
CC       galactose free diet (PubMed:22124465). {ECO:0000269|PubMed:22124465,
CC       ECO:0000269|PubMed:28974690}.
CC   -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC       family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AK085602; BAC39483.1; -; mRNA.
DR   CCDS; CCDS19199.1; -.
DR   RefSeq; NP_062784.3; NM_019810.4.
DR   AlphaFoldDB; Q8C3K6; -.
DR   SMR; Q8C3K6; -.
DR   IntAct; Q8C3K6; 1.
DR   STRING; 10090.ENSMUSP00000011178; -.
DR   DrugCentral; Q8C3K6; -.
DR   GuidetoPHARMACOLOGY; 915; -.
DR   GlyCosmos; Q8C3K6; 1 site, No reported glycans.
DR   GlyGen; Q8C3K6; 1 site.
DR   iPTMnet; Q8C3K6; -.
DR   PhosphoSitePlus; Q8C3K6; -.
DR   jPOST; Q8C3K6; -.
DR   MaxQB; Q8C3K6; -.
DR   PaxDb; 10090-ENSMUSP00000011178; -.
DR   PeptideAtlas; Q8C3K6; -.
DR   ProteomicsDB; 255345; -.
DR   DNASU; 20537; -.
DR   GeneID; 20537; -.
DR   KEGG; mmu:20537; -.
DR   AGR; MGI:107678; -.
DR   CTD; 6523; -.
DR   MGI; MGI:107678; Slc5a1.
DR   eggNOG; KOG2349; Eukaryota.
DR   InParanoid; Q8C3K6; -.
DR   OrthoDB; 74094at2759; -.
DR   PhylomeDB; Q8C3K6; -.
DR   Reactome; R-MMU-189200; Cellular hexose transport.
DR   Reactome; R-MMU-8981373; Intestinal hexose absorption.
DR   BioGRID-ORCS; 20537; 2 hits in 77 CRISPR screens.
DR   ChiTaRS; Slc5a1; mouse.
DR   PRO; PR:Q8C3K6; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8C3K6; Protein.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005903; C:brush border; IDA:MGI.
DR   GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR   GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR   GO; GO:0005769; C:early endosome; ISO:MGI.
DR   GO; GO:0043229; C:intracellular organelle; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0015151; F:alpha-glucoside transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0055056; F:D-glucose transmembrane transporter activity; ISO:MGI.
DR   GO; GO:0015371; F:galactose:sodium symporter activity; ISS:UniProtKB.
DR   GO; GO:0005355; F:glucose transmembrane transporter activity; IMP:MGI.
DR   GO; GO:0005412; F:glucose:sodium symporter activity; IDA:UniProtKB.
DR   GO; GO:0005372; F:water transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0000017; P:alpha-glucoside transport; ISO:MGI.
DR   GO; GO:0098708; P:glucose import across plasma membrane; ISO:MGI.
DR   GO; GO:1904659; P:glucose transmembrane transport; IMP:MGI.
DR   GO; GO:0050892; P:intestinal absorption; IDA:MGI.
DR   GO; GO:0001951; P:intestinal D-glucose absorption; IMP:UniProtKB.
DR   GO; GO:0001656; P:metanephros development; IMP:MGI.
DR   GO; GO:0035623; P:renal glucose absorption; IMP:UniProtKB.
DR   GO; GO:0010035; P:response to inorganic substance; ISO:MGI.
DR   GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
DR   GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR   GO; GO:0035377; P:transepithelial water transport; ISO:MGI.
DR   GO; GO:0150104; P:transport across blood-brain barrier; ISO:MGI.
DR   Gene3D; 1.20.1730.10; Sodium/glucose cotransporter; 1.
DR   InterPro; IPR038377; Na/Glc_symporter_sf.
DR   InterPro; IPR001734; Na/solute_symporter.
DR   InterPro; IPR018212; Na/solute_symporter_CS.
DR   NCBIfam; TIGR00813; sss; 1.
DR   PANTHER; PTHR11819:SF151; SODIUM_GLUCOSE COTRANSPORTER 1; 1.
DR   PANTHER; PTHR11819; SOLUTE CARRIER FAMILY 5; 1.
DR   Pfam; PF00474; SSF; 1.
DR   PROSITE; PS00456; NA_SOLUT_SYMP_1; 1.
DR   PROSITE; PS00457; NA_SOLUT_SYMP_2; 1.
DR   PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Ion transport; Membrane;
KW   Phosphoprotein; Reference proteome; Sodium; Sodium transport;
KW   Sugar transport; Symport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..665
FT                   /note="Sodium/glucose cotransporter 1"
FT                   /id="PRO_0000105367"
FT   TOPO_DOM        1..28
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        29..49
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        50..64
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        65..85
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        86..105
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        106..126
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        127..142
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        143..163
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        164..178
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        179..201
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        202..208
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        209..229
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        230..277
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        278..298
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        299..313
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        314..334
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        335..380
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        381..401
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        402..423
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        424..444
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        445..455
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        456..476
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        477..484
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        485..505
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        506..526
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        527..563
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        564..644
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        645..665
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         457
FT                   /ligand="D-glucose"
FT                   /ligand_id="ChEBI:CHEBI:4167"
FT                   /evidence="ECO:0000250"
FT   SITE            43
FT                   /note="Implicated in sodium coupling"
FT                   /evidence="ECO:0000250"
FT   SITE            300
FT                   /note="Implicated in sodium coupling"
FT                   /evidence="ECO:0000250"
FT   SITE            460
FT                   /note="Involved in sugar-binding/transport and inhibitor
FT                   binding"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         585
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         588
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   CARBOHYD        248
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        255..611
FT                   /evidence="ECO:0000250"
FT   DISULFID        255..511
FT                   /evidence="ECO:0000250|UniProtKB:P13866"
FT   DISULFID        345..351
FT                   /evidence="ECO:0000250|UniProtKB:P13866"
FT   DISULFID        355..361
FT                   /evidence="ECO:0000250|UniProtKB:P13866"
FT   DISULFID        517..522
FT                   /evidence="ECO:0000250|UniProtKB:P13866"
SQ   SEQUENCE   665 AA;  73449 MW;  70905E30408BE378 CRC64;
     MDSSTLSPAV TATDAPIPSY ERIRNAADIS VIVIYFVVVM AVGLWAMFST NRGTVGGFFL
     AGRSMVWWPI GASLFASNIG SGHFVGLAGT GAAAGIAMGG FEWNALVLVV VLGWIFVPIY
     IKAGVVTMPE YLRKRFGGKR IQIYLSVLSL LLYIFTKISA DIFSGAIFIN LALGLDIYLA
     IFILLAITAL YTITGGLAAV IYTDTLQTAI MLVGSFILTG FAFNEVGGYE AFMDKYMKAI
     PTKVSNGNFT AKEECYTPRA DSFHIFRDPI TGDMPWPGLI FGLAILALWY WCTDQVIVQR
     CLSAKNMSHV KADCTLCGYL KLLPMFLMVM PGMISRILYT EKIACVLPEE CQKYCGTPVG
     CTNIAYPTLV VELMPNGLRG LMLSVMMASL MSSLTSIFNS ASTLFTMDIY TKIRKKASEK
     ELMIAGRLFI LVLIGISIAW VPIVQSAQSG QLFDYIQSIT SYLGPPIAAV FLLAIFCKRV
     NEQGAFWGLI LGFLIGISRM ITEFAYGTGS CMEPSNCPKI ICGVHYLYFA IILFVISVIT
     ILIISFLTKP IPDVHLYRWC WSLRNSKEER IDLDAGEEED IPEDSKDTIE IDTEAPQKKK
     GCFRRAYDLF CGLDQDKGPK MTKEEEEAMK MKMTDTSEKP LWRTVVNING IILLAVAVFC
     HAYFA
//