SC5A1_MOUSE
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 03-AUG-2022, entry version 129.
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}.
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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 GlyGen; Q8C3K6; 1 site.
DR iPTMnet; Q8C3K6; -.
DR PhosphoSitePlus; Q8C3K6; -.
DR jPOST; Q8C3K6; -.
DR MaxQB; Q8C3K6; -.
DR PaxDb; Q8C3K6; -.
DR PeptideAtlas; Q8C3K6; -.
DR PRIDE; Q8C3K6; -.
DR ProteomicsDB; 255345; -.
DR DNASU; 20537; -.
DR GeneID; 20537; -.
DR KEGG; mmu:20537; -.
DR CTD; 6523; -.
DR MGI; MGI:107678; Slc5a1.
DR eggNOG; KOG2349; Eukaryota.
DR InParanoid; Q8C3K6; -.
DR OrthoDB; 243316at2759; -.
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 72 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:0016021; C:integral component of membrane; IBA:GO_Central.
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:0032409; P:regulation of transporter activity; IDA: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; -; 1.
DR InterPro; IPR038377; Na/Glc_symporter_sf.
DR InterPro; IPR001734; Na/solute_symporter.
DR InterPro; IPR018212; Na/solute_symporter_CS.
DR Pfam; PF00474; SSF; 1.
DR TIGRFAMs; TIGR00813; sss; 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
