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Sodium/glucose cotransporter 2 (Na( )/glucose cotransporter 2) (Low affinity sodium-glucose cotransporter) (Solute carrier family 5 member 2)

 SC5A2_HUMAN             Reviewed;         672 AA.
P31639; A2RRD2;
01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
01-JUL-1993, sequence version 1.
25-APR-2018, entry version 163.
RecName: Full=Sodium/glucose cotransporter 2;
Short=Na(+)/glucose cotransporter 2;
AltName: Full=Low affinity sodium-glucose cotransporter;
AltName: Full=Solute carrier family 5 member 2;
Name=SLC5A2; Synonyms=SGLT2 {ECO:0000303|PubMed:14614622};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Kidney;
PubMed=1415574;
Wells R.G., Pajor A.M., Kanai Y., Turk E., Wright E.M., Hediger M.A.;
"Cloning of a human kidney cDNA with similarity to the sodium-glucose
cotransporter.";
Am. J. Physiol. 263:F459-F465(1992).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15616553; DOI=10.1038/nature03187;
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
Rubin E.M., Pennacchio L.A.;
"The sequence and analysis of duplication-rich human chromosome 16.";
Nature 432:988-994(2004).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
VARIANT GLYS SER-654.
PubMed=14614622; DOI=10.1007/s00439-003-1054-x;
Calado J., Soto K., Clemente C., Correia P., Rueff J.;
"Novel compound heterozygous mutations in SLC5A2 are responsible for
autosomal recessive renal glucosuria.";
Hum. Genet. 114:314-316(2004).
-!- FUNCTION: Sodium-dependent glucose transporter. Has a Na(+) to
glucose coupling ratio of 1:1.
-!- FUNCTION: Efficient substrate transport in mammalian kidney is
provided by the concerted action of a low affinity high capacity
and a high affinity low capacity Na(+)/glucose cotransporter
arranged in series along kidney proximal tubules.
-!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P31639-1; Sequence=Displayed;
Name=2;
IsoId=P31639-2; Sequence=VSP_056333, VSP_056334;
Note=No experimental confirmation available.;
-!- DISEASE: Renal glucosuria (GLYS) [MIM:233100]: A disorder
characterized by persistent isolated glucosuria, normal fasting
serum glucose concentration, decreased renal tubular resorption of
glucose from the urine, and absence of any other signs of tubular
dysfunction. {ECO:0000269|PubMed:14614622}. Note=The disease is
caused by mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC
2.A.21) family. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; M95549; AAA36608.1; -; mRNA.
EMBL; AC026471; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC131542; AAI31543.1; -; mRNA.
CCDS; CCDS10714.1; -. [P31639-1]
PIR; A56765; A56765.
RefSeq; NP_003032.1; NM_003041.3. [P31639-1]
UniGene; Hs.709195; -.
ProteinModelPortal; P31639; -.
BioGrid; 112415; 1.
STRING; 9606.ENSP00000327943; -.
BindingDB; P31639; -.
ChEMBL; CHEMBL3884; -.
DrugBank; DB08907; Canagliflozin.
DrugBank; DB06292; Dapagliflozin.
DrugBank; DB09038; Empagliflozin.
GuidetoPHARMACOLOGY; 916; -.
TCDB; 2.A.21.3.16; the solute:sodium symporter (sss) family.
CarbonylDB; P31639; -.
iPTMnet; P31639; -.
PhosphoSitePlus; P31639; -.
BioMuta; SLC5A2; -.
DMDM; 400337; -.
PaxDb; P31639; -.
PeptideAtlas; P31639; -.
PRIDE; P31639; -.
Ensembl; ENST00000330498; ENSP00000327943; ENSG00000140675. [P31639-1]
Ensembl; ENST00000419665; ENSP00000410601; ENSG00000140675. [P31639-2]
GeneID; 6524; -.
KEGG; hsa:6524; -.
UCSC; uc002ecf.5; human. [P31639-1]
CTD; 6524; -.
DisGeNET; 6524; -.
EuPathDB; HostDB:ENSG00000140675.12; -.
GeneCards; SLC5A2; -.
HGNC; HGNC:11037; SLC5A2.
HPA; HPA041603; -.
MalaCards; SLC5A2; -.
MIM; 182381; gene.
MIM; 233100; phenotype.
neXtProt; NX_P31639; -.
OpenTargets; ENSG00000140675; -.
Orphanet; 69076; Renal glucosuria.
PharmGKB; PA35902; -.
eggNOG; ENOG410IP49; Eukaryota.
eggNOG; COG4146; LUCA.
GeneTree; ENSGT00760000118955; -.
HOGENOM; HOG000025422; -.
HOVERGEN; HBG052859; -.
InParanoid; P31639; -.
KO; K14382; -.
OMA; GWYWCSD; -.
OrthoDB; EOG091G077U; -.
PhylomeDB; P31639; -.
TreeFam; TF352855; -.
Reactome; R-HSA-189200; Cellular hexose transport.
Reactome; R-HSA-5658208; Defective SLC5A2 causes renal glucosuria (GLYS1).
SIGNOR; P31639; -.
ChiTaRS; SLC5A2; human.
GeneWiki; SLC5A2; -.
GenomeRNAi; 6524; -.
PRO; PR:P31639; -.
Proteomes; UP000005640; Chromosome 16.
Bgee; ENSG00000140675; -.
CleanEx; HS_SLC5A2; -.
ExpressionAtlas; P31639; baseline and differential.
Genevisible; P31639; HS.
GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0005412; F:glucose:sodium symporter activity; EXP:Reactome.
GO; GO:0005362; F:low-affinity glucose:sodium symporter activity; TAS:ProtInc.
GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
GO; GO:0008645; P:hexose transmembrane transport; TAS:Reactome.
Gene3D; 1.20.1730.10; -; 1.
InterPro; IPR038377; Na/Glc_symporter_sf.
InterPro; IPR001734; Na/solute_symporter.
InterPro; IPR018212; Na/solute_symporter_CS.
Pfam; PF00474; SSF; 1.
TIGRFAMs; TIGR00813; sss; 1.
PROSITE; PS00456; NA_SOLUT_SYMP_1; 1.
PROSITE; PS00457; NA_SOLUT_SYMP_2; 1.
PROSITE; PS50283; NA_SOLUT_SYMP_3; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Disease mutation;
Glycoprotein; Ion transport; Membrane; Reference proteome; Sodium;
Sodium transport; Sugar transport; Symport; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 672 Sodium/glucose cotransporter 2.
/FTId=PRO_0000105372.
TOPO_DOM 1 25 Cytoplasmic. {ECO:0000255}.
TRANSMEM 26 44 Helical. {ECO:0000255}.
TOPO_DOM 45 61 Extracellular. {ECO:0000255}.
TRANSMEM 62 82 Helical. {ECO:0000255}.
TOPO_DOM 83 102 Cytoplasmic. {ECO:0000255}.
TRANSMEM 103 123 Helical. {ECO:0000255}.
TOPO_DOM 124 168 Extracellular. {ECO:0000255}.
TRANSMEM 169 188 Helical. {ECO:0000255}.
TOPO_DOM 189 205 Cytoplasmic. {ECO:0000255}.
TRANSMEM 206 226 Helical. {ECO:0000255}.
TOPO_DOM 227 270 Extracellular. {ECO:0000255}.
TRANSMEM 271 291 Helical. {ECO:0000255}.
TOPO_DOM 292 314 Cytoplasmic. {ECO:0000255}.
TRANSMEM 315 334 Helical. {ECO:0000255}.
TOPO_DOM 335 423 Extracellular. {ECO:0000255}.
TRANSMEM 424 443 Helical. {ECO:0000255}.
TOPO_DOM 444 455 Cytoplasmic. {ECO:0000255}.
TRANSMEM 456 476 Helical. {ECO:0000255}.
TOPO_DOM 477 526 Extracellular. {ECO:0000255}.
TRANSMEM 527 547 Helical. {ECO:0000255}.
TOPO_DOM 548 650 Cytoplasmic. {ECO:0000255}.
TRANSMEM 651 671 Helical. {ECO:0000255}.
SITE 40 40 Implicated in sodium coupling.
{ECO:0000250}.
SITE 300 300 Implicated in sodium coupling.
{ECO:0000250}.
CARBOHYD 250 250 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 399 399 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
VAR_SEQ 378 458 LRGLMLAVMLAALMSSLASIFNSSSTLFTMDIYTRLRPRAG
DRELLLVGRLWVVFIVVVSVAWLPVVQAAQGGQLFDYIQA
-> RLLGTHRGPADGPGTPDSRVLLRLGQLCAALGVPSFPL
RRALPLLRHCAVLLLWPPHPHGLPVHRAHPQKAPPPPGLQS
PA (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_056333.
VAR_SEQ 459 672 Missing (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_056334.
VARIANT 654 654 N -> S (in GLYS; dbSNP:rs61742739).
{ECO:0000269|PubMed:14614622}.
/FTId=VAR_019310.
SEQUENCE 672 AA; 72897 MW; 233C65F1601B0337 CRC64;
MEEHTEAGSA PEMGAQKALI DNPADILVIA AYFLLVIGVG LWSMCRTNRG TVGGYFLAGR
SMVWWPVGAS LFASNIGSGH FVGLAGTGAA SGLAVAGFEW NALFVVLLLG WLFAPVYLTA
GVITMPQYLR KRFGGRRIRL YLSVLSLFLY IFTKISVDMF SGAVFIQQAL GWNIYASVIA
LLGITMIYTV TGGLAALMYT DTVQTFVILG GACILMGYAF HEVGGYSGLF DKYLGAATSL
TVSEDPAVGN ISSFCYRPRP DSYHLLRHPV TGDLPWPALL LGLTIVSGWY WCSDQVIVQR
CLAGKSLTHI KAGCILCGYL KLTPMFLMVM PGMISRILYP DEVACVVPEV CRRVCGTEVG
CSNIAYPRLV VKLMPNGLRG LMLAVMLAAL MSSLASIFNS SSTLFTMDIY TRLRPRAGDR
ELLLVGRLWV VFIVVVSVAW LPVVQAAQGG QLFDYIQAVS SYLAPPVSAV FVLALFVPRV
NEQGAFWGLI GGLLMGLARL IPEFSFGSGS CVQPSACPAF LCGVHYLYFA IVLFFCSGLL
TLTVSLCTAP IPRKHLHRLV FSLRHSKEER EDLDADEQQG SSLPVQNGCP ESAMEMNEPQ
APAPSLFRQC LLWFCGMSRG GVGSPPPLTQ EEAAAAARRL EDISEDPSWA RVVNLNALLM
MAVAVFLWGF YA


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