SC5A2_MOUSE
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 03-AUG-2022, entry version 145.
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, 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 GlyGen; Q923I7; 1 site.
DR iPTMnet; Q923I7; -.
DR PhosphoSitePlus; Q923I7; -.
DR jPOST; Q923I7; -.
DR MaxQB; Q923I7; -.
DR PaxDb; Q923I7; -.
DR PRIDE; Q923I7; -.
DR ProteomicsDB; 255346; -.
DR Antibodypedia; 27902; 216 antibodies from 32 providers.
DR DNASU; 246787; -.
DR Ensembl; ENSMUST00000118169; ENSMUSP00000112597; ENSMUSG00000030781.
DR GeneID; 246787; -.
DR KEGG; mmu:246787; -.
DR UCSC; uc009jyu.1; mouse.
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; LEYWMAV; -.
DR OrthoDB; 243316at2759; -.
DR PhylomeDB; Q923I7; -.
DR TreeFam; TF352855; -.
DR Reactome; R-MMU-189200; Cellular hexose transport.
DR BioGRID-ORCS; 246787; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q923I7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q923I7; protein.
DR Bgee; ENSMUSG00000030781; Expressed in right kidney and 235 other tissues.
DR ExpressionAtlas; Q923I7; baseline and differential.
DR Genevisible; Q923I7; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of 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; -; 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; 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
