ID   SC5A2_MOUSE             Reviewed;         670 AA.
AC   Q923I7;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Sodium/glucose cotransporter 2;
DE            Short=Na(+)/glucose cotransporter 2;
DE   AltName: Full=Low affinity sodium-glucose cotransporter;
DE   AltName: Full=Solute carrier family 5 member 2;
GN   Name=Slc5a2;
GN   Synonyms=Sglt2 {ECO:0000303|PubMed:11749115,
GN   ECO:0000303|PubMed:15489334};
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].
RC   STRAIN=C57BL/6J;
RX   PubMed=11749115; DOI=10.1006/taap.2001.9321;
RA   Tabatabai N.M., Blumenthal S.S., Lewand D.L., Petering D.H.;
RT   "Differential regulation of mouse kidney sodium-dependent transporters mRNA
RT   by cadmium.";
RL   Toxicol. Appl. Pharmacol. 177:163-173(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
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   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   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=20616166; DOI=10.1681/asn.2010030246;
RA   Vallon V., Platt K.A., Cunard R., Schroth J., Whaley J., Thomson S.C.,
RA   Koepsell H., Rieg T.;
RT   "SGLT2 mediates glucose reabsorption in the early proximal tubule.";
RL   J. Am. Soc. Nephrol. 22:104-112(2011).
CC   -!- FUNCTION: Electrogenic Na(+)-coupled sugar simporter that actively
CC       transports D-glucose at the plasma membrane, with a Na(+) to sugar
CC       coupling ratio of 1:1. Transporter activity is driven by a
CC       transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump
CC       (By similarity). Has a primary role in D-glucose reabsorption from
CC       glomerular filtrate across the brush border of the early proximal
CC       tubules of the kidney (PubMed:20616166). {ECO:0000250|UniProtKB:P31639,
CC       ECO:0000269|PubMed:20616166}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=D-glucose(out) + Na(+)(out) = D-glucose(in) + Na(+)(in);
CC         Xref=Rhea:RHEA:70571, ChEBI:CHEBI:4167, ChEBI:CHEBI:29101;
CC         Evidence={ECO:0000250|UniProtKB:P31639};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70572;
CC         Evidence={ECO:0000250|UniProtKB:P31639};
CC   -!- SUBUNIT: Forms a heterodimer with PDZK1IP1; this interaction enhances
CC       the transporter activity over a hundred-fold.
CC       {ECO:0000250|UniProtKB:P31639}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:20616166}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in epithelial cells of early proximal
CC       tubules (at protein level). {ECO:0000269|PubMed:20616166}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice develop glucosuria associated with
CC       increased food and fluid intake. {ECO:0000269|PubMed:20616166}.
CC   -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC       family. {ECO:0000305}.
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DR   EMBL; AY033886; AAK61606.1; -; mRNA.
DR   EMBL; BC022226; AAH22226.1; -; mRNA.
DR   CCDS; CCDS21894.1; -.
DR   RefSeq; NP_573517.1; NM_133254.3.
DR   AlphaFoldDB; Q923I7; -.
DR   SMR; Q923I7; -.
DR   STRING; 10090.ENSMUSP00000112597; -.
DR   BindingDB; Q923I7; -.
DR   ChEMBL; CHEMBL1075302; -.
DR   DrugCentral; Q923I7; -.
DR   GuidetoPHARMACOLOGY; 916; -.
DR   GlyCosmos; Q923I7; 1 site, No reported glycans.
DR   GlyGen; Q923I7; 1 site.
DR   iPTMnet; Q923I7; -.
DR   PhosphoSitePlus; Q923I7; -.
DR   jPOST; Q923I7; -.
DR   MaxQB; Q923I7; -.
DR   PaxDb; 10090-ENSMUSP00000112597; -.
DR   ProteomicsDB; 255346; -.
DR   Antibodypedia; 27902; 238 antibodies from 32 providers.
DR   DNASU; 246787; -.
DR   Ensembl; ENSMUST00000118169.8; ENSMUSP00000112597.2; ENSMUSG00000030781.14.
DR   GeneID; 246787; -.
DR   KEGG; mmu:246787; -.
DR   UCSC; uc009jyu.1; mouse.
DR   AGR; MGI:2181411; -.
DR   CTD; 6524; -.
DR   MGI; MGI:2181411; Slc5a2.
DR   VEuPathDB; HostDB:ENSMUSG00000030781; -.
DR   eggNOG; KOG2349; Eukaryota.
DR   GeneTree; ENSGT00940000160533; -.
DR   HOGENOM; CLU_018808_9_2_1; -.
DR   InParanoid; Q923I7; -.
DR   OMA; TTIGWDT; -.
DR   OrthoDB; 74094at2759; -.
DR   PhylomeDB; Q923I7; -.
DR   TreeFam; TF352855; -.
DR   Reactome; R-MMU-189200; Cellular hexose transport.
DR   BioGRID-ORCS; 246787; 1 hit in 77 CRISPR screens.
DR   PRO; PR:Q923I7; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q923I7; Protein.
DR   Bgee; ENSMUSG00000030781; Expressed in right kidney and 237 other cell types or tissues.
DR   ExpressionAtlas; Q923I7; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0031526; C:brush border membrane; 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:0005412; F:glucose:sodium symporter 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; ISO:MGI.
DR   GO; GO:0035811; P:negative regulation of urine volume; ISO:MGI.
DR   GO; GO:0035623; P:renal glucose absorption; IMP:UniProtKB.
DR   GO; GO:0036359; P:renal potassium excretion; 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   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:SF145; SODIUM_GLUCOSE COTRANSPORTER 2; 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.
DR   Genevisible; Q923I7; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Glycoprotein; Ion transport; Membrane; Reference proteome;
KW   Sodium; Sodium transport; Sugar transport; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..670
FT                   /note="Sodium/glucose cotransporter 2"
FT                   /id="PRO_0000105373"
FT   TOPO_DOM        1..23
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        24..42
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        43..59
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        60..80
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        81..100
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        101..121
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        122..166
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        167..187
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        188..203
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        204..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        225..268
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        269..289
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        290..312
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        313..332
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        333..421
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        422..441
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        442..453
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        454..474
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        475..524
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        525..545
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        546..648
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        649..669
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        248
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   670 AA;  73008 MW;  66BD6E48889E15DF CRC64;
     MEQHVEAGSE LGEQKVLIDN PADILVIAAY FLLVIGVGLW SMFRTNRGTV GGYFLAGRSM
     VWWPVGASLF ASNIGSGHFV GLAGTGAASG LAVAGFEWNA LFVVLLLGWL FVPVYLTAGV
     ITMPQYLRKR FGGHRIRLYL SVLSLFLYIF TKISVDMFSG AVFIQQALGW NIYASVIALL
     GITMIYTVTG GLAALMYTDT VQTFVILAGA FILTGYAFHE VGGYSGLFDK YLGAMTSLTV
     SKDPSVGNIS STCYQPRPDS YHLLRDPVTG DLPWPALLLG LTIVSGWYWC SDQVIVQRCL
     AGKNLTHIKA GCILCGYLKL MPMFLMVMPG MISRILYPDE VACVVPEVCK RVCGTEVGCS
     NIAYPRLVVK LMPNGLRGLM LAVMLAALMS SLASIFNSSS TLFTMDIYTR LRPRAGDKEL
     LLVGRLWVVF IVAVSVAWLP VVQAAQGGQL FDYIQSVSSY LAPPVSAVFV LALFVPRVNE
     KGAFWGLVGG LLMGLARLIP EFFFGSGSCV RPSACPALFC RVHYLYFAII LFICSGILTL
     GISLCTAPIP QKHLHRLVFS LRHSKEERED LDADELEGPA PAPVQNGGQE CAMEMEEVQS
     PAPGLLRRCL LWFCGMSKSG SGSPPPTTEE VAATTRRLED ISEDPRWARV VNLNALLMMT
     VAVFLWGFYA
//