SC5A1_RABIT
ID SC5A1_RABIT Reviewed; 662 AA.
AC P11170;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 125.
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; Synonyms=SGLT1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white;
RX PubMed=2446136; DOI=10.1038/330379a0;
RA Hediger M.A., Coady M.J., Ikeda T.S., Wright E.M.;
RT "Expression cloning and cDNA sequencing of the Na+/glucose co-
RT transporter.";
RL Nature 330:379-381(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Kidney cortex;
RX PubMed=2025641; DOI=10.1016/0167-4781(91)90093-2;
RA Morrison A.I., Panayotova-Heiermann M., Feigl G., Schoelermann B.,
RA Kinne R.K.H.;
RT "Sequence comparison of the sodium-D-glucose cotransport systems in rabbit
RT renal and intestinal epithelia.";
RL Biochim. Biophys. Acta 1089:121-123(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 178-662, AND TISSUE SPECIFICITY.
RX PubMed=2221040; DOI=10.1152/ajpcell.1990.259.4.c605;
RA Coady M.J., Pajor A.M., Wright E.M.;
RT "Sequence homologies among intestinal and renal Na+/glucose
RT cotransporters.";
RL Am. J. Physiol. 259:C605-C610(1990).
RN [4]
RP TOPOLOGY, AND DISULFIDE BOND.
RX PubMed=17616521; DOI=10.1074/jbc.m704190200;
RA Puntheeranurak T., Kasch M., Xia X., Hinterdorfer P., Kinne R.K.;
RT "Three surface subdomains form the vestibule of the Na+/glucose
RT cotransporter SGLT1.";
RL J. Biol. Chem. 282:25222-25230(2007).
RN [5]
RP TOPOLOGY, SUBSTRATE-BINDING SITE, AND MUTAGENESIS OF GLN-457 AND THR-460.
RX PubMed=20692230; DOI=10.1016/j.bbamem.2010.07.028;
RA Tyagi N.K., Puntheeranurak T., Raja M., Kumar A., Wimmer B.,
RA Neundlinger I., Gruber H., Hinterdorfer P., Kinne R.K.;
RT "A biophysical glance at the outer surface of the membrane transporter
RT SGLT1.";
RL Biochim. Biophys. Acta 1808:1-18(2011).
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 (By similarity). Has a primary role in the transport of dietary
CC monosaccharides from enterocytes to blood. Responsible for the
CC absorption of D-glucose or D-galactose across the apical brush-border
CC membrane of enterocytes, whereas basolateral exit is provided by GLUT2.
CC Additionally, functions as a D-glucose sensor in enteroendocrine cells,
CC triggering the secretion of the incretins GCG and GIP that control food
CC intake and energy homeostasis (By similarity). Together with SGLT2,
CC functions in reabsorption of D-glucose from glomerular filtrate,
CC playing a nonredundant role in the S3 segment of the proximal tubules
CC (By similarity). Transports D-glucose into endometrial epithelial
CC cells, controlling glycogen synthesis and nutritional support for the
CC embryo as well as the decidual transformation of endometrium prior to
CC conception (By similarity). Acts as a water channel enabling passive
CC water transport in response to the osmotic gradient created upon sugar
CC and Na(+) uptake. Has high water conductivity comparable to aquaporins
CC and therefore is expected to play an important role in transepithelial
CC water permeability, especially in the small intestine.
CC {ECO:0000250|UniProtKB:P13866, ECO:0000250|UniProtKB:Q8C3K6}.
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:0000250|UniProtKB:P13866};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70496;
CC Evidence={ECO:0000250|UniProtKB:P13866};
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:0000250|UniProtKB:Q8C3K6}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Found predominantly in intestine, renal cortex and
CC in outer renal medulla. {ECO:0000269|PubMed:2221040}.
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 -!- DISEASE: Note=Mutation of Asp-28 is implicated in glucose/galactose
CC malabsorption.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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DR EMBL; X06419; CAA29727.1; -; mRNA.
DR EMBL; X55355; CAA39040.1; -; mRNA.
DR PIR; S00515; A37226.
DR RefSeq; NP_001095162.1; NM_001101692.1.
DR AlphaFoldDB; P11170; -.
DR SMR; P11170; -.
DR STRING; 9986.ENSOCUP00000015091; -.
DR PRIDE; P11170; -.
DR GeneID; 100009262; -.
DR KEGG; ocu:100009262; -.
DR CTD; 6523; -.
DR eggNOG; KOG2349; Eukaryota.
DR InParanoid; P11170; -.
DR OrthoDB; 243316at2759; -.
DR PRO; PR:P11170; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015151; F:alpha-glucoside transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015150; F:fucose transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005354; F:galactose transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015371; F:galactose:sodium symporter activity; ISS:UniProtKB.
DR GO; GO:0005412; F:glucose:sodium symporter activity; IDA:ARUK-UCL.
DR GO; GO:0005367; F:myo-inositol:sodium symporter activity; IDA:ARUK-UCL.
DR GO; GO:0015146; F:pentose transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005372; F:water transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0000017; P:alpha-glucoside transport; IDA:ARUK-UCL.
DR GO; GO:0015756; P:fucose transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0015757; P:galactose transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:1904659; P:glucose transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0001951; P:intestinal D-glucose absorption; ISS:UniProtKB.
DR GO; GO:0015798; P:myo-inositol transport; IDA:ARUK-UCL.
DR GO; GO:0015750; P:pentose transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0035623; P:renal glucose absorption; ISS:UniProtKB.
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 Reference proteome; Sodium; Sodium transport; Sugar transport; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..662
FT /note="Sodium/glucose cotransporter 1"
FT /id="PRO_0000105369"
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..641
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 642..662
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 457
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000305"
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 CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 255..608
FT /evidence="ECO:0000269|PubMed:17616521"
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"
FT MUTAGEN 457
FT /note="Q->W: Drasticly decreased affinity for glucose and
FT phlorizin."
FT /evidence="ECO:0000269|PubMed:20692230"
FT MUTAGEN 460
FT /note="T->W: Decreased affinity for glucose and phlorizin."
FT /evidence="ECO:0000269|PubMed:20692230"
SQ SEQUENCE 662 AA; 73079 MW; 03F55A0309CBBE01 CRC64;
MDSSTLSPLT TSTAAPLESY ERIRNAADIS VIVIYFLVVM AVGLWAMFST NRGTVGGFFL
AGRSMVWWPI GASLFASNIG SGHFVGLAGT GAASGIATGG FEWNALIMVV VLGWVFVPIY
IRAGVVTMPE YLQKRFGGKR IQIYLSILSL LLYIFTKISA DIFSGAIFIQ LTLGLDIYVA
IIILLVITGL YTITGGLAAV IYTDTLQTAI MMVGSVILTG FAFHEVGGYE AFTEKYMRAI
PSQISYGNTS IPQKCYTPRE DAFHIFRDAI TGDIPWPGLV FGMSILTLWY WCTDQVIVQR
CLSAKNLSHV KAGCILCGYL KVMPMFLIVM MGMVSRILYT DKVACVVPSE CERYCGTRVG
CTNIAFPTLV VELMPNGLRG LMLSVMMASL MSSLTSIFNS ASTLFTMDIY TKIRKKASEK
ELMIAGRLFM LFLIGISIAW VPIVQSAQSG QLFDYIQSIT SYLGPPIAAV FLLAIFWKRV
NEPGAFWGLV LGFLIGISRM ITEFAYGTGS CMEPSNCPTI ICGVHYLYFA IILFVISIIT
VVVVSLFTKP IPDVHLYRLC WSLRNSKEER IDLDAGEEDI QEAPEEATDT EVPKKKKGFF
RRAYDLFCGL DQDKGPKMTK EEEAAMKLKL TDTSEHPLWR TVVNINGVIL LAVAVFCYAY
FA
