ID   SC5A1_HUMAN             Reviewed;         664 AA.
AC   P13866;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1990, sequence version 1.
DT   10-JUN-2008, entry version 90.
DE   Sodium/glucose cotransporter 1 (Na(+)/glucose cotransporter 1) (High
DE   affinity sodium-glucose cotransporter) (Solute carrier family 5 member
DE   1).
GN   Name=SLC5A1; Synonyms=NAGT, SGLT1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=89345544; PubMed=2490366;
RA   Hediger M.A., Turk E., Wright E.M.;
RT   "Homology of the human intestinal Na+/glucose and Escherichia coli
RT   Na+/proline cotransporters.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:5748-5752(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GGM GLY-28.
RX   MEDLINE=94253082; PubMed=8195156;
RA   Turk E., Martin M.G., Wright E.M.;
RT   "Structure of the human Na+/glucose cotransporter gene SGLT1.";
RL   J. Biol. Chem. 269:15204-15209(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:RESEARCH84.1-RESEARCH84.11(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=20057165; PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA   Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA   Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA   Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA   Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA   Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA   Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA   Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA   Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA   Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA   Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA   Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA   Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA   Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA   Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA   Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA   Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA   Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA   Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA   Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA   Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA   Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA   Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA   Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA   Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA   Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA   Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA   Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA   Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA   Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA   Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA   Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA   O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA   Khan A.S., Lane L., Tilahun Y., Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [5]
RP   TOPOLOGY, MUTAGENESIS OF ASN-248, AND GLYCOSYLATION AT ASN-248.
RX   MEDLINE=96147162; PubMed=8567640; DOI=10.1074/jbc.271.4.1925;
RA   Turk E., Kerner C.J., Lostao M.P., Wright E.M.;
RT   "Membrane topology of the human Na+/glucose cotransporter SGLT1.";
RL   J. Biol. Chem. 271:1925-1934(1996).
RN   [6]
RP   VARIANT GGM ASN-28.
RX   MEDLINE=91179516; PubMed=2008213; DOI=10.1038/350354a0;
RA   Turk E., Zabel B., Mundlos S., Dyer J., Wright E.M.;
RT   "Glucose/galactose malabsorption caused by a defect in the Na+/glucose
RT   cotransporter.";
RL   Nature 350:354-356(1991).
RN   [7]
RP   VARIANTS GGM ARG-318 AND VAL-468.
RX   MEDLINE=99156772; PubMed=10036327; DOI=10.1016/S0925-4439(98)00109-4;
RA   Lam J.T., Martin M.G., Turk E., Hirayama B.A., Bosshard N.U.,
RA   Steinmann B., Wright E.M.;
RT   "Missense mutations in SGLT1 cause glucose-galactose malabsorption by
RT   trafficking defects.";
RL   Biochim. Biophys. Acta 1453:297-303(1999).
RN   [8]
RP   VARIANT GGM TRP-135.
RX   MEDLINE=21299072; PubMed=11406349; DOI=10.1016/S0925-4439(01)00043-6;
RA   Kasahara M., Maeda M., Hayashi S., Mori Y., Abe T.;
RT   "A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in
RT   a patient with congenital glucose-galactose malabsorption: normal
RT   trafficking but inactivation of the mutant protein.";
RL   Biochim. Biophys. Acta 1536:141-147(2001).
CC   -!- FUNCTION: Actively transports glucose into cells by Na(+)
CC       cotransport with a Na(+) to glucose coupling ratio of 2:1.
CC       Efficient substrate transport in mammalian kidney is provided by
CC       the concerted action of a low affinity high capacity and a high
CC       affinity low capacity Na(+)/glucose cotransporter arranged in
CC       series along kidney proximal tubules.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed mainly in intestine and kidney.
CC   -!- PTM: N-glycosylation is not necessary for the cotransporter
CC       function.
CC   -!- DISEASE: Defects in SLC5A1 are the cause of congenital
CC       glucose/galactose malabsorption (GGM) [MIM:606824]. GGM is an
CC       intestinal monosaccharide transporter deficiency. It is an
CC       autosomal recessive disorder manifesting itself within the first
CC       weeks of life. It is characterized by severe diarrhea and
CC       dehydration which are usually fatal unless glucose and galactose
CC       are eliminated from the diet.
CC   -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF)
CC       (TC 2.A.21) family.
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DR   EMBL; M24847; AAA60320.1; -; mRNA.
DR   EMBL; L29339; AAB59448.1; -; Genomic_DNA.
DR   EMBL; L29328; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29330; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29329; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29331; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29332; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29333; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29334; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29335; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29336; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29337; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; L29338; AAB59448.1; JOINED; Genomic_DNA.
DR   EMBL; CR456579; CAG30465.1; -; mRNA.
DR   EMBL; AL022321; CAI19810.1; -; Genomic_DNA.
DR   EMBL; Z74021; CAI19810.1; JOINED; Genomic_DNA.
DR   EMBL; Z80998; CAI19810.1; JOINED; Genomic_DNA.
DR   EMBL; Z83839; CAI19810.1; JOINED; Genomic_DNA.
DR   EMBL; Z83849; CAI19810.1; JOINED; Genomic_DNA.
DR   EMBL; Z74021; CAI18756.1; -; Genomic_DNA.
DR   EMBL; AL022321; CAI18756.1; JOINED; Genomic_DNA.
DR   EMBL; Z80998; CAI18756.1; JOINED; Genomic_DNA.
DR   EMBL; Z83839; CAI18756.1; JOINED; Genomic_DNA.
DR   EMBL; Z83849; CAI18756.1; JOINED; Genomic_DNA.
DR   EMBL; Z80998; CAI18759.1; -; Genomic_DNA.
DR   EMBL; AL022321; CAI18759.1; JOINED; Genomic_DNA.
DR   EMBL; Z74021; CAI18759.1; JOINED; Genomic_DNA.
DR   EMBL; Z83839; CAI18759.1; JOINED; Genomic_DNA.
DR   EMBL; Z83849; CAI18759.1; JOINED; Genomic_DNA.
DR   EMBL; Z83839; CAB06087.1; -; Genomic_DNA.
DR   EMBL; AL022321; CAB06087.1; JOINED; Genomic_DNA.
DR   EMBL; Z74021; CAB06087.1; JOINED; Genomic_DNA.
DR   EMBL; Z80998; CAB06087.1; JOINED; Genomic_DNA.
DR   EMBL; Z83849; CAB06087.1; JOINED; Genomic_DNA.
DR   EMBL; Z83849; CAI23589.1; -; Genomic_DNA.
DR   EMBL; AL022321; CAI23589.1; JOINED; Genomic_DNA.
DR   EMBL; Z74021; CAI23589.1; JOINED; Genomic_DNA.
DR   EMBL; Z80998; CAI23589.1; JOINED; Genomic_DNA.
DR   EMBL; Z83839; CAI23589.1; JOINED; Genomic_DNA.
DR   PIR; A33545; A33545.
DR   RefSeq; NP_000334.1; -.
DR   UniGene; Hs.1964; -.
DR   Ensembl; ENSG00000100170; Homo sapiens.
DR   GeneID; 6523; -.
DR   KEGG; hsa:6523; -.
DR   H-InvDB; HIX0026944; -.
DR   H-InvDB; HIX0029229; -.
DR   H-InvDB; HIX0041191; -.
DR   HGNC; HGNC:11036; SLC5A1.
DR   MIM; 182380; gene.
DR   MIM; 606824; phenotype.
DR   Orphanet; 35710; Glucose-galactose malabsorption.
DR   PharmGKB; PA308; -.
DR   HOGENOM; P13866; -.
DR   HOVERGEN; P13866; -.
DR   LinkHub; P13866; -.
DR   ArrayExpress; P13866; -.
DR   CleanEx; HS_SLC5A1; -.
DR   GermOnline; ENSG00000100170; Homo sapiens.
DR   GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR   GO; GO:0005412; F:glucose:sodium symporter activity; IDA:MGI.
DR   GO; GO:0015758; P:glucose transport; IMP:MGI.
DR   InterPro; IPR001734; Na/solut_symport.
DR   PANTHER; PTHR11819; Na/solut_symport; 1.
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   Disease mutation; Glycoprotein; Ion transport; Membrane; Polymorphism;
KW   Sodium; Sodium transport; Sugar transport; Symport; Transmembrane;
KW   Transport.
FT   CHAIN         1    664       Sodium/glucose cotransporter 1.
FT                                /FTId=PRO_0000105366.
FT   TOPO_DOM      1     28       Extracellular (Potential).
FT   TRANSMEM     29     49       Potential.
FT   TOPO_DOM     50     64       Cytoplasmic (Potential).
FT   TRANSMEM     65     85       Potential.
FT   TOPO_DOM     86    105       Extracellular (Potential).
FT   TRANSMEM    106    126       Potential.
FT   TOPO_DOM    127    142       Cytoplasmic (Potential).
FT   TRANSMEM    143    163       Potential.
FT   TOPO_DOM    164    178       Extracellular (Potential).
FT   TRANSMEM    179    201       Potential.
FT   TOPO_DOM    202    208       Cytoplasmic (Potential).
FT   TRANSMEM    209    229       Potential.
FT   TOPO_DOM    230    277       Extracellular (Potential).
FT   TRANSMEM    278    298       Potential.
FT   TOPO_DOM    299    313       Cytoplasmic (Potential).
FT   TRANSMEM    314    334       Potential.
FT   TOPO_DOM    335    380       Extracellular (Potential).
FT   TRANSMEM    381    401       Potential.
FT   TOPO_DOM    402    423       Cytoplasmic (Potential).
FT   TRANSMEM    424    444       Potential.
FT   TOPO_DOM    445    455       Extracellular (Potential).
FT   TRANSMEM    456    476       Potential.
FT   TOPO_DOM    477    484       Cytoplasmic (Potential).
FT   TRANSMEM    485    505       Potential.
FT   TOPO_DOM    506    526       Extracellular (Potential).
FT   TRANSMEM    527    547       Potential.
FT   TOPO_DOM    548    643       Cytoplasmic (Potential).
FT   TRANSMEM    644    664       Potential.
FT   SITE         43     43       Implicated in sodium coupling (By
FT                                similarity).
FT   SITE        300    300       Implicated in sodium coupling (By
FT                                similarity).
FT   CARBOHYD    248    248       N-linked (GlcNAc...).
FT   VARIANT      28     28       D -> G (in GGM).
FT                                /FTId=VAR_013630.
FT   VARIANT      28     28       D -> N (in GGM).
FT                                /FTId=VAR_007168.
FT   VARIANT      51     51       N -> S (in dbSNP:rs17683011).
FT                                /FTId=VAR_029147.
FT   VARIANT     135    135       R -> W (in GGM; loss of activity).
FT                                /FTId=VAR_021502.
FT   VARIANT     318    318       G -> R (in GGM).
FT                                /FTId=VAR_021503.
FT   VARIANT     411    411       A -> T (in dbSNP:rs17683430).
FT                                /FTId=VAR_029148.
FT   VARIANT     468    468       A -> V (in GGM).
FT                                /FTId=VAR_021504.
FT   MUTAGEN     248    248       N->Q: Loss of N-glycosylation.
SQ   SEQUENCE   664 AA;  73498 MW;  2B403376595EAB74 CRC64;
     MDSSTWSPKT TAVTRPVETH ELIRNAADIS IIVIYFVVVM AVGLWAMFST NRGTVGGFFL
     AGRSMVWWPI GASLFASNIG SGHFVGLAGT GAASGIAIGG FEWNALVLVV VLGWLFVPIY
     IKAGVVTMPE YLRKRFGGQR IQVYLSLLSL LLYIFTKISA DIFSGAIFIN LALGLNLYLA
     IFLLLAITAL YTITGGLAAV IYTDTLQTVI MLVGSLILTG FAFHEVGGYD AFMEKYMKAI
     PTIVSDGNTT FQEKCYTPRA DSFHIFRDPL TGDLPWPGFI FGMSILTLWY WCTDQVIVQR
     CLSAKNMSHV KGGCILCGYL KLMPMFIMVM PGMISRILYT EKIACVVPSE CEKYCGTKVG
     CTNIAYPTLV VELMPNGLRG LMLSVMLASL MSSLTSIFNS ASTLFTMDIY AKVRKRASEK
     ELMIAGRLFI LVLIGISIAW VPIVQSAQSG QLFDYIQSIT SYLGPPIAAV FLLAIFWKRV
     NEPGAFWGLI LGLLIGISRM ITEFAYGTGS CMEPSNCPTI ICGVHYLYFA IILFAISFIT
     IVVISLLTKP IPDVHLYRLC WSLRNSKEER IDLDAEEENI QEGPKETIEI ETQVPEKKKG
     IFRRAYDLFC GLEQHGAPKM TEEEEKAMKM KMTDTSEKPL WRTVLNVNGI ILVTVAVFCH
     AYFA
//
