SC5A1_HUMAN
ID SC5A1_HUMAN Reviewed; 664 AA.
AC P13866; B2R7E2; B7Z4Q9; B7ZA69;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Sodium/glucose cotransporter 1;
DE Short=Na(+)/glucose cotransporter 1 {ECO:0000303|PubMed:8563765};
DE AltName: Full=High affinity sodium-glucose cotransporter;
DE AltName: Full=Solute carrier family 5 member 1;
GN Name=SLC5A1 {ECO:0000303|PubMed:28974690, ECO:0000312|HGNC:HGNC:11036};
GN Synonyms=NAGT, SGLT1 {ECO:0000303|PubMed:8563765};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=2490366; DOI=10.1073/pnas.86.15.5748;
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 PubMed=8195156; DOI=10.1016/s0021-9258(17)36592-4;
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] (ISOFORM 1).
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:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Heart, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., 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., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., 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., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TOPOLOGY, MUTAGENESIS OF ASN-248, AND GLYCOSYLATION AT ASN-248.
RX 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 [8]
RP FUNCTION.
RX PubMed=14695256; DOI=10.1016/s0006-3495(04)74090-4;
RA Gagnon M.P., Bissonnette P., Deslandes L.M., Wallendorff B., Lapointe J.Y.;
RT "Glucose accumulation can account for the initial water flux triggered by
RT Na+/glucose cotransport.";
RL Biophys. J. 86:125-133(2004).
RN [9]
RP FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=20980548; DOI=10.1152/ajpcell.00388.2010;
RA Hummel C.S., Lu C., Loo D.D., Hirayama B.A., Voss A.A., Wright E.M.;
RT "Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and
RT SGLT2.";
RL Am. J. Physiol. 300:C14-C21(2011).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-292.
RX PubMed=26945065; DOI=10.1074/jbc.m115.706986;
RA Erokhova L., Horner A., Ollinger N., Siligan C., Pohl P.;
RT "The Sodium Glucose Cotransporter SGLT1 Is an Extremely Efficient
RT Facilitator of Passive Water Transport.";
RL J. Biol. Chem. 291:9712-9720(2016).
RN [11]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=28974690; DOI=10.1038/s41598-017-11674-3;
RA Salker M.S., Singh Y., Zeng N., Chen H., Zhang S., Umbach A.T., Fakhri H.,
RA Kohlhofer U., Quintanilla-Martinez L., Durairaj R.R.P., Barros F.S.V.,
RA Vrljicak P., Ott S., Brucker S.Y., Wallwiener D., Vrhovac Madunic I.,
RA Breljak D., Sabolic I., Koepsell H., Brosens J.J., Lang F.;
RT "Loss of Endometrial Sodium Glucose Cotransporter SGLT1 is Detrimental to
RT Embryo Survival and Fetal Growth in Pregnancy.";
RL Sci. Rep. 7:12612-12612(2017).
RN [12]
RP FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF HIS-83; THR-287; TYR-290 AND LYS-321.
RX PubMed=35077764; DOI=10.1016/j.jmb.2022.167464;
RA Kamitori K., Shirota M., Fujiwara Y.;
RT "Structural basis of the selective sugar transport in sodium-glucose
RT cotransporters.";
RL J. Mol. Biol. 434:167464-167464(2022).
RN [13]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.15 ANGSTROMS) IN COMPLEX WITH
RP CHOLESTEROL, DISULFIDE BOND, FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY
RP REGULATION, DOMAIN, AND MUTAGENESIS OF TRP-67; SER-77; HIS-83; ASP-204;
RP THR-287; TRP-291; ASN-363; SER-396; GLN-451; LEU-452; ASP-454; GLN-457;
RP THR-460; TRP-641; HIS-660 AND ALA-661.
RX PubMed=34880492; DOI=10.1038/s41586-021-04211-w;
RA Han L., Qu Q., Aydin D., Panova O., Robertson M.J., Xu Y., Dror R.O.,
RA Skiniotis G., Feng L.;
RT "Structure and mechanism of the SGLT family of glucose transporters.";
RL Nature 601:274-279(2022).
RN [14]
RP VARIANT GGM ASN-28.
RX 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 [15]
RP VARIANTS GGM ASN-28; GLY-28; SER-51; TRP-135; PRO-159; THR-166;
RP 191-TYR--ALA-664 DEL; 254-LYS--ALA-664 DEL; LEU-276; TYR-292; ARG-295;
RP SER-300; VAL-304; SER-369; 379-ARG--ALA-664 DEL; GLN-379; VAL-388; SER-405;
RP THR-411; ARG-426; ASN-470; HIS-499 AND GLN-615, FUNCTION, AND TRANSPORTER
RP ACTIVITY.
RX PubMed=8563765; DOI=10.1038/ng0296-216;
RA Martin M.G., Turk E., Lostao M.P., Kerner C., Wright E.M.;
RT "Defects in Na+/glucose cotransporter (SGLT1) trafficking and function
RT cause glucose-galactose malabsorption.";
RL Nat. Genet. 12:216-220(1996).
RN [16]
RP VARIANTS GGM ARG-318 AND VAL-468.
RX 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., Steinmann B.,
RA 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 [17]
RP VARIANT GGM TRP-135.
RX 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 a
RT patient with congenital glucose-galactose malabsorption: normal trafficking
RT but inactivation of the mutant protein.";
RL Biochim. Biophys. Acta 1536:141-147(2001).
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 (PubMed:20980548, PubMed:35077764, PubMed:8563765,
CC PubMed:34880492). 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 (PubMed:8563765) (By similarity).
CC Together with SGLT2, functions in reabsorption of D-glucose from
CC glomerular filtrate, playing a nonredundant role in the S3 segment of
CC the proximal tubules (By similarity). Transports D-glucose into
CC endometrial epithelial cells, controlling glycogen synthesis and
CC nutritional support for the embryo as well as the decidual
CC transformation of endometrium prior to conception (PubMed:28974690).
CC Acts as a water channel enabling passive water transport across the
CC plasma membrane in response to the osmotic gradient created upon sugar
CC and Na(+) uptake. Has high water conductivity, comparable to
CC aquaporins, and therefore is expected to play an important role in
CC transepithelial water permeability, especially in the small intestine.
CC {ECO:0000250|UniProtKB:Q8C3K6, ECO:0000269|PubMed:14695256,
CC ECO:0000269|PubMed:20980548, ECO:0000269|PubMed:26945065,
CC ECO:0000269|PubMed:28974690, ECO:0000269|PubMed:34880492,
CC ECO:0000269|PubMed:35077764, ECO:0000269|PubMed:8563765}.
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:0000269|PubMed:35077764};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70496;
CC Evidence={ECO:0000305|PubMed:20980548, ECO:0000305|PubMed:34880492,
CC ECO:0000305|PubMed:35077764, ECO:0000305|PubMed:8563765};
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:0000269|PubMed:34880492, ECO:0000269|PubMed:35077764};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70500;
CC Evidence={ECO:0000305|PubMed:20980548, ECO:0000305|PubMed:34880492,
CC ECO:0000305|PubMed:35077764};
CC -!- ACTIVITY REGULATION: Inhibited by phlorizin (PubMed:20980548,
CC PubMed:34880492). Possibly modulated by cholesterol binding
CC (PubMed:34880492). {ECO:0000269|PubMed:20980548,
CC ECO:0000269|PubMed:34880492}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.74 mM for D-glucose {ECO:0000269|PubMed:35077764};
CC KM=3.12 mM for D-galactose {ECO:0000269|PubMed:35077764};
CC -!- INTERACTION:
CC P13866; P00533: EGFR; NbExp=3; IntAct=EBI-1772443, EBI-297353;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:26945065}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13866-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13866-2; Sequence=VSP_044782;
CC -!- TISSUE SPECIFICITY: Expressed in intestine (PubMed:2490366). Expressed
CC in endometrial cells (PubMed:28974690). {ECO:0000269|PubMed:2490366,
CC ECO:0000269|PubMed:28974690}.
CC -!- INDUCTION: Up-regulated upon transition of the endometrium from the
CC non-receptive early secretory phase to the receptive mid-secretory
CC phase of the cycle. {ECO:0000269|PubMed:28974690}.
CC -!- DOMAIN: The cholesterol-binding site is formed by transmembrane helices
CC TM1, TM7 and TM13. {ECO:0000269|PubMed:34880492}.
CC -!- PTM: N-glycosylation is not necessary for the cotransporter function.
CC {ECO:0000269|PubMed:8567640}.
CC -!- DISEASE: Congenital glucose/galactose malabsorption (GGM) [MIM:606824]:
CC Intestinal monosaccharide transporter deficiency. It is an autosomal
CC recessive disorder manifesting itself within the first weeks of life.
CC It is characterized by severe diarrhea and dehydration which are
CC usually fatal unless glucose and galactose are eliminated from the
CC diet. {ECO:0000269|PubMed:10036327, ECO:0000269|PubMed:11406349,
CC ECO:0000269|PubMed:2008213, ECO:0000269|PubMed:8195156,
CC ECO:0000269|PubMed:8563765}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21)
CC family. {ECO:0000305}.
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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; AK297665; BAH12645.1; -; mRNA.
DR EMBL; AK312948; BAG35789.1; -; mRNA.
DR EMBL; AK316184; BAH14555.1; -; mRNA.
DR EMBL; AL022321; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z74021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z80998; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z83849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60006.1; -; Genomic_DNA.
DR CCDS; CCDS13902.1; -. [P13866-1]
DR CCDS; CCDS58805.1; -. [P13866-2]
DR PIR; A33545; A33545.
DR RefSeq; NP_000334.1; NM_000343.3. [P13866-1]
DR RefSeq; NP_001243243.1; NM_001256314.1. [P13866-2]
DR AlphaFoldDB; P13866; -.
DR SMR; P13866; -.
DR BioGRID; 112414; 28.
DR IntAct; P13866; 1.
DR STRING; 9606.ENSP00000266088; -.
DR BindingDB; P13866; -.
DR ChEMBL; CHEMBL4979; -.
DR DrugBank; DB00766; Clavulanic acid.
DR DrugBank; DB01914; D-glucose.
DR DrugBank; DB09341; Dextrose, unspecified form.
DR DrugCentral; P13866; -.
DR GuidetoPHARMACOLOGY; 915; -.
DR TCDB; 2.A.21.3.1; the solute:sodium symporter (sss) family.
DR GlyGen; P13866; 4 sites, 5 O-linked glycans (3 sites).
DR iPTMnet; P13866; -.
DR PhosphoSitePlus; P13866; -.
DR BioMuta; SLC5A1; -.
DR DMDM; 127803; -.
DR EPD; P13866; -.
DR jPOST; P13866; -.
DR MassIVE; P13866; -.
DR MaxQB; P13866; -.
DR PaxDb; P13866; -.
DR PeptideAtlas; P13866; -.
DR PRIDE; P13866; -.
DR ProteomicsDB; 52997; -. [P13866-1]
DR ProteomicsDB; 6623; -.
DR Antibodypedia; 25191; 370 antibodies from 35 providers.
DR DNASU; 6523; -.
DR Ensembl; ENST00000266088.9; ENSP00000266088.4; ENSG00000100170.10. [P13866-1]
DR Ensembl; ENST00000543737.2; ENSP00000444898.1; ENSG00000100170.10. [P13866-2]
DR GeneID; 6523; -.
DR KEGG; hsa:6523; -.
DR MANE-Select; ENST00000266088.9; ENSP00000266088.4; NM_000343.4; NP_000334.1.
DR UCSC; uc003amc.4; human. [P13866-1]
DR CTD; 6523; -.
DR DisGeNET; 6523; -.
DR GeneCards; SLC5A1; -.
DR HGNC; HGNC:11036; SLC5A1.
DR HPA; ENSG00000100170; Tissue enriched (intestine).
DR MalaCards; SLC5A1; -.
DR MIM; 182380; gene.
DR MIM; 606824; phenotype.
DR neXtProt; NX_P13866; -.
DR OpenTargets; ENSG00000100170; -.
DR Orphanet; 35710; Glucose-galactose malabsorption.
DR PharmGKB; PA308; -.
DR VEuPathDB; HostDB:ENSG00000100170; -.
DR eggNOG; KOG2349; Eukaryota.
DR GeneTree; ENSGT00940000155844; -.
DR HOGENOM; CLU_018808_9_2_1; -.
DR InParanoid; P13866; -.
DR OMA; AYMTMVT; -.
DR OrthoDB; 243316at2759; -.
DR PhylomeDB; P13866; -.
DR TreeFam; TF352855; -.
DR PathwayCommons; P13866; -.
DR Reactome; R-HSA-189200; Cellular hexose transport.
DR Reactome; R-HSA-5656364; Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM).
DR Reactome; R-HSA-8981373; Intestinal hexose absorption.
DR SignaLink; P13866; -.
DR SIGNOR; P13866; -.
DR BioGRID-ORCS; 6523; 12 hits in 1060 CRISPR screens.
DR ChiTaRS; SLC5A1; human.
DR GeneWiki; SLC5A1; -.
DR GenomeRNAi; 6523; -.
DR Pharos; P13866; Tclin.
DR PRO; PR:P13866; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P13866; protein.
DR Bgee; ENSG00000100170; Expressed in jejunal mucosa and 114 other tissues.
DR Genevisible; P13866; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0031526; C:brush border membrane; ISS:ARUK-UCL.
DR GO; GO:0005769; C:early endosome; IDA:ARUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043229; C:intracellular organelle; ISS:ARUK-UCL.
DR GO; GO:0097708; C:intracellular vesicle; TAS:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0015151; F:alpha-glucoside transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0055056; F:D-glucose transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015150; F:fucose transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005354; F:galactose transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015371; F:galactose:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0005355; F:glucose transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0005412; F:glucose:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0005367; F:myo-inositol:sodium symporter activity; ISS:ARUK-UCL.
DR GO; GO:0015146; F:pentose transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005372; F:water transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0000017; P:alpha-glucoside transport; IDA:ARUK-UCL.
DR GO; GO:0015756; P:fucose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0015757; P:galactose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0098708; P:glucose import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:1904659; P:glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:0001951; P:intestinal D-glucose absorption; ISS:UniProtKB.
DR GO; GO:0106001; P:intestinal hexose absorption; TAS:Reactome.
DR GO; GO:0015798; P:myo-inositol transport; ISS:ARUK-UCL.
DR GO; GO:0015750; P:pentose transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0035623; P:renal glucose absorption; ISS:UniProtKB.
DR GO; GO:0010035; P:response to inorganic substance; IDA:ARUK-UCL.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0006814; P:sodium ion transport; IBA:GO_Central.
DR GO; GO:0035377; P:transepithelial water transport; IDA:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; IGI:ARUK-UCL.
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 Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sodium; Sodium transport; Sugar transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..664
FT /note="Sodium/glucose cotransporter 1"
FT /id="PRO_0000105366"
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..643
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 644..664
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 457
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000250"
FT MOD_RES 587
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8C3K6"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8567640"
FT DISULFID 255..511
FT /evidence="ECO:0000269|PubMed:34880492"
FT DISULFID 345..351
FT /evidence="ECO:0000269|PubMed:34880492"
FT DISULFID 355..361
FT /evidence="ECO:0000269|PubMed:34880492"
FT DISULFID 517..522
FT /evidence="ECO:0000269|PubMed:34880492"
FT VAR_SEQ 1..127
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044782"
FT VARIANT 28
FT /note="D -> G (in GGM; dbSNP:rs121912669)"
FT /evidence="ECO:0000269|PubMed:8195156,
FT ECO:0000269|PubMed:8563765"
FT /id="VAR_013630"
FT VARIANT 28
FT /note="D -> N (in GGM; dbSNP:rs121912668)"
FT /evidence="ECO:0000269|PubMed:2008213,
FT ECO:0000269|PubMed:8563765"
FT /id="VAR_007168"
FT VARIANT 51
FT /note="N -> S (in GGM; slightly decreased activity;
FT dbSNP:rs17683011)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_029147"
FT VARIANT 135
FT /note="R -> W (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:11406349,
FT ECO:0000269|PubMed:8563765"
FT /id="VAR_021502"
FT VARIANT 159
FT /note="S -> P (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086053"
FT VARIANT 166
FT /note="A -> T (in GGM; about 90% reduction in activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086054"
FT VARIANT 191..664
FT /note="Missing (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086055"
FT VARIANT 254..664
FT /note="Missing (in GGM)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086056"
FT VARIANT 276
FT /note="W -> L (in GGM; about 95% reduction in activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086057"
FT VARIANT 292
FT /note="C -> Y (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086058"
FT VARIANT 295
FT /note="Q -> R (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086059"
FT VARIANT 300
FT /note="R -> S (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086060"
FT VARIANT 304
FT /note="A -> V (in GGM; impairs trafficking to the plasma
FT membrane)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086061"
FT VARIANT 318
FT /note="G -> R (in GGM; dbSNP:rs371505974)"
FT /evidence="ECO:0000269|PubMed:10036327"
FT /id="VAR_021503"
FT VARIANT 369
FT /note="L -> S (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086062"
FT VARIANT 379..664
FT /note="Missing (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086063"
FT VARIANT 379
FT /note="R -> Q (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086064"
FT VARIANT 388
FT /note="A -> V (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086065"
FT VARIANT 405
FT /note="F -> S (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086066"
FT VARIANT 411
FT /note="A -> T (in GGM; slightly decreased activity;
FT dbSNP:rs17683430)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_029148"
FT VARIANT 426
FT /note="G -> R (in GGM; loss of activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086067"
FT VARIANT 468
FT /note="A -> V (in GGM; dbSNP:rs200406921)"
FT /evidence="ECO:0000269|PubMed:10036327"
FT /id="VAR_021504"
FT VARIANT 470
FT /note="V -> N (in GGM; requires 2 nucleotide substitutions;
FT about 90% reduction in activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086068"
FT VARIANT 499
FT /note="R -> H (in GGM; impairs trafficking to the plasma
FT membrane; decreases the sugar affinity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086069"
FT VARIANT 615
FT /note="H -> Q (in GGM; slightly decreased activity)"
FT /evidence="ECO:0000269|PubMed:8563765"
FT /id="VAR_086070"
FT MUTAGEN 67
FT /note="W->A: Strong reduction in D-glucose transporter
FT activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 77
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 83
FT /note="H->L: Acquires D-mannose, D-fructose and L-sorbose
FT transporter activity; when associated with A-287 and C-
FT 290."
FT /evidence="ECO:0000269|PubMed:35077764"
FT MUTAGEN 83
FT /note="H->Q: Loss of D-glucose transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 204
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 248
FT /note="N->Q: Loss of N-glycosylation."
FT /evidence="ECO:0000269|PubMed:8567640"
FT MUTAGEN 287
FT /note="T->A: Acquires D-mannose, D-fructose and L-sorbose
FT transporter activity; when associated with L-83 and C-290."
FT /evidence="ECO:0000269|PubMed:35077764"
FT MUTAGEN 287
FT /note="T->N: Loss of D-glucose transporter activity. Has
FT strict selectivity for D-galactose."
FT /evidence="ECO:0000269|PubMed:34880492,
FT ECO:0000269|PubMed:35077764"
FT MUTAGEN 287
FT /note="T->S,A: Has normal D-glucose and D-galactose
FT transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492,
FT ECO:0000269|PubMed:35077764"
FT MUTAGEN 290
FT /note="Y->C: Loss of D-galactose transporter activity. Has
FT strict selectivity for D-glucose. Acquires D-mannose, D-
FT fructose and L-sorbose transporter activity; when
FT associated with A-287 and L-83."
FT /evidence="ECO:0000269|PubMed:35077764"
FT MUTAGEN 291
FT /note="W->A: Loss of D-glucose transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 292
FT /note="C->A: Has no effect on water permeability."
FT /evidence="ECO:0000269|PubMed:26945065"
FT MUTAGEN 321
FT /note="K->Q: Acquires D-mannose and D-allose transporter
FT activity comparable to glucose and galactose."
FT /evidence="ECO:0000269|PubMed:35077764"
FT MUTAGEN 363
FT /note="N->A: Loss of water permeation."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 396
FT /note="S->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 451
FT /note="Q->A: Strong reduction in water permeation."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 452
FT /note="L->A: Loss of water permeation."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 454
FT /note="D->A: Has no effect on water permeation."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 457
FT /note="Q->A: Loss of D-glucose transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 457
FT /note="Q->C: Strong reduction in D-glucose transporter
FT activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 460
FT /note="T->A: Loss of D-glucose transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 641
FT /note="W->A: Slightly reduced D-glucose transporter
FT activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT MUTAGEN 660..661
FT /note="HA->WG: Loss of D-glucose transporter activity."
FT /evidence="ECO:0000269|PubMed:34880492"
FT CONFLICT 631
FT /note="K -> R (in Ref. 4; BAH14555)"
FT /evidence="ECO:0000305"
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
