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P13866 (SC5A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/glucose cotransporter 1

Short name=Na(+)/glucose cotransporter 1
Alternative name(s):
High affinity sodium-glucose cotransporter
Solute carrier family 5 member 1
Gene names
Name:SLC5A1
Synonyms:NAGT, SGLT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length664 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Actively transports glucose into cells by Na+ cotransport with a Na+ to glucose coupling ratio of 2:1. 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.

Tissue specificity

Expressed mainly in intestine and kidney.

Post-translational modification

N-glycosylation is not necessary for the cotransporter function.

Involvement in disease

Congenital glucose/galactose malabsorption (GGM) [MIM:606824]: Intestinal monosaccharide transporter deficiency. It is an autosomal recessive disorder manifesting itself within the first weeks of life. It is characterized by severe diarrhea and dehydration which are usually fatal unless glucose and galactose are eliminated from the diet.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family. [View classification]

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EGFRP005333EBI-1772443,EBI-297353

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P13866-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P13866-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 664664Sodium/glucose cotransporter 1
PRO_0000105366

Regions

Topological domain1 – 2828Extracellular Potential
Transmembrane29 – 4921Helical; Potential
Topological domain50 – 6415Cytoplasmic Potential
Transmembrane65 – 8521Helical; Potential
Topological domain86 – 10520Extracellular Potential
Transmembrane106 – 12621Helical; Potential
Topological domain127 – 14216Cytoplasmic Potential
Transmembrane143 – 16321Helical; Potential
Topological domain164 – 17815Extracellular Potential
Transmembrane179 – 20123Helical; Potential
Topological domain202 – 2087Cytoplasmic Potential
Transmembrane209 – 22921Helical; Potential
Topological domain230 – 27748Extracellular Potential
Transmembrane278 – 29821Helical; Potential
Topological domain299 – 31315Cytoplasmic Potential
Transmembrane314 – 33421Helical; Potential
Topological domain335 – 38046Extracellular Potential
Transmembrane381 – 40121Helical; Potential
Topological domain402 – 42322Cytoplasmic Potential
Transmembrane424 – 44421Helical; Potential
Topological domain445 – 45511Extracellular Potential
Transmembrane456 – 47621Helical; Potential
Topological domain477 – 4848Cytoplasmic Potential
Transmembrane485 – 50521Helical; Potential
Topological domain506 – 52621Extracellular Potential
Intramembrane527 – 56337Helical; Potential
Topological domain564 – 64380Extracellular Potential
Transmembrane644 – 66421Helical; Potential

Sites

Binding site4571Glucose By similarity
Site431Implicated in sodium coupling By similarity
Site3001Implicated in sodium coupling By similarity
Site4601Involved in sugar-binding/transport and inhibitor binding By similarity

Amino acid modifications

Glycosylation2481N-linked (GlcNAc...) Ref.7
Disulfide bond255 ↔ 610 By similarity

Natural variations

Alternative sequence1 – 127127Missing in isoform 2.
VSP_044782
Natural variant281D → G in GGM. Ref.2
VAR_013630
Natural variant281D → N in GGM. Ref.8
VAR_007168
Natural variant511N → S.
Corresponds to variant rs17683011 [ dbSNP | Ensembl ].
VAR_029147
Natural variant1351R → W in GGM; loss of activity. Ref.10
VAR_021502
Natural variant3181G → R in GGM. Ref.9
VAR_021503
Natural variant4111A → T.
Corresponds to variant rs17683430 [ dbSNP | Ensembl ].
VAR_029148
Natural variant4681A → V in GGM. Ref.9
VAR_021504

Experimental info

Mutagenesis2481N → Q: Loss of N-glycosylation. Ref.7
Sequence conflict6311K → R in BAH14555. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1990. Version 1.
Checksum: 2B403376595EAB74

FASTA66473,498
        10         20         30         40         50         60 
MDSSTWSPKT TAVTRPVETH ELIRNAADIS IIVIYFVVVM AVGLWAMFST NRGTVGGFFL 

        70         80         90        100        110        120 
AGRSMVWWPI GASLFASNIG SGHFVGLAGT GAASGIAIGG FEWNALVLVV VLGWLFVPIY 

       130        140        150        160        170        180 
IKAGVVTMPE YLRKRFGGQR IQVYLSLLSL LLYIFTKISA DIFSGAIFIN LALGLNLYLA 

       190        200        210        220        230        240 
IFLLLAITAL YTITGGLAAV IYTDTLQTVI MLVGSLILTG FAFHEVGGYD AFMEKYMKAI 

       250        260        270        280        290        300 
PTIVSDGNTT FQEKCYTPRA DSFHIFRDPL TGDLPWPGFI FGMSILTLWY WCTDQVIVQR 

       310        320        330        340        350        360 
CLSAKNMSHV KGGCILCGYL KLMPMFIMVM PGMISRILYT EKIACVVPSE CEKYCGTKVG 

       370        380        390        400        410        420 
CTNIAYPTLV VELMPNGLRG LMLSVMLASL MSSLTSIFNS ASTLFTMDIY AKVRKRASEK 

       430        440        450        460        470        480 
ELMIAGRLFI LVLIGISIAW VPIVQSAQSG QLFDYIQSIT SYLGPPIAAV FLLAIFWKRV 

       490        500        510        520        530        540 
NEPGAFWGLI LGLLIGISRM ITEFAYGTGS CMEPSNCPTI ICGVHYLYFA IILFAISFIT 

       550        560        570        580        590        600 
IVVISLLTKP IPDVHLYRLC WSLRNSKEER IDLDAEEENI QEGPKETIEI ETQVPEKKKG 

       610        620        630        640        650        660 
IFRRAYDLFC GLEQHGAPKM TEEEEKAMKM KMTDTSEKPL WRTVLNVNGI ILVTVAVFCH 


AYFA 

« Hide

Isoform 2 [UniParc].

Checksum: F7B5A898E54C9476
Show »

FASTA53760,097

References

« Hide 'large scale' references
[1]"Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters."
Hediger M.A., Turk E., Wright E.M.
Proc. Natl. Acad. Sci. U.S.A. 86:5748-5752(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structure of the human Na+/glucose cotransporter gene SGLT1."
Turk E., Martin M.G., Wright E.M.
J. Biol. Chem. 269:15204-15209(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GGM GLY-28.
[3]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Heart and Trachea.
[5]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Membrane topology of the human Na+/glucose cotransporter SGLT1."
Turk E., Kerner C.J., Lostao M.P., Wright E.M.
J. Biol. Chem. 271:1925-1934(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: TOPOLOGY, MUTAGENESIS OF ASN-248, GLYCOSYLATION AT ASN-248.
[8]"Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter."
Turk E., Zabel B., Mundlos S., Dyer J., Wright E.M.
Nature 350:354-356(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GGM ASN-28.
[9]"Missense mutations in SGLT1 cause glucose-galactose malabsorption by trafficking defects."
Lam J.T., Martin M.G., Turk E., Hirayama B.A., Bosshard N.U., Steinmann B., Wright E.M.
Biochim. Biophys. Acta 1453:297-303(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GGM ARG-318 AND VAL-468.
[10]"A missense mutation in the Na(+)/glucose cotransporter gene SGLT1 in a patient with congenital glucose-galactose malabsorption: normal trafficking but inactivation of the mutant protein."
Kasahara M., Maeda M., Hayashi S., Mori Y., Abe T.
Biochim. Biophys. Acta 1536:141-147(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GGM TRP-135.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M24847 mRNA. Translation: AAA60320.1.
L29339 expand/collapse EMBL AC list , L29328, L29330, L29329, L29331, L29332, L29333, L29334, L29335, L29336, L29337, L29338 Genomic DNA. Translation: AAB59448.1.
CR456579 mRNA. Translation: CAG30465.1.
AK297665 mRNA. Translation: BAH12645.1.
AK312948 mRNA. Translation: BAG35789.1.
AK316184 mRNA. Translation: BAH14555.1.
AL022321 expand/collapse EMBL AC list , Z74021, Z80998, Z83839, Z83849 Genomic DNA. Translation: CAI19810.1.
Z74021 expand/collapse EMBL AC list , AL022321, Z80998, Z83839, Z83849 Genomic DNA. Translation: CAI18756.1.
Z80998 expand/collapse EMBL AC list , AL022321, Z74021, Z83839, Z83849 Genomic DNA. Translation: CAI18759.1.
Z83839 expand/collapse EMBL AC list , AL022321, Z74021, Z80998, Z83849 Genomic DNA. Translation: CAB06087.1.
Z83849 expand/collapse EMBL AC list , AL022321, Z74021, Z80998, Z83839 Genomic DNA. Translation: CAI23589.1.
CH471095 Genomic DNA. Translation: EAW60006.1.
PIRA33545.
RefSeqNP_000334.1. NM_000343.3.
NP_001243243.1. NM_001256314.1.
UniGeneHs.1964.

3D structure databases

ProteinModelPortalP13866.
SMRP13866. Positions 26-553.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112414. 2 interactions.
IntActP13866. 1 interaction.
STRING9606.ENSP00000266088.

Chemistry

BindingDBP13866.
ChEMBLCHEMBL4979.
GuidetoPHARMACOLOGY915.

Protein family/group databases

TCDB2.A.21.3.1. the solute:sodium symporter (sss) family.

PTM databases

PhosphoSiteP13866.

Polymorphism databases

DMDM127803.

Proteomic databases

PaxDbP13866.
PRIDEP13866.

Protocols and materials databases

DNASU6523.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266088; ENSP00000266088; ENSG00000100170. [P13866-1]
ENST00000543737; ENSP00000444898; ENSG00000100170. [P13866-2]
GeneID6523.
KEGGhsa:6523.
UCSCuc003amc.3. human. [P13866-1]

Organism-specific databases

CTD6523.
GeneCardsGC22P032439.
HGNCHGNC:11036. SLC5A1.
HPACAB015467.
HPA051805.
MIM182380. gene.
606824. phenotype.
neXtProtNX_P13866.
Orphanet35710. Glucose-galactose malabsorption.
PharmGKBPA308.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4146.
HOVERGENHBG052859.
InParanoidP13866.
KOK14158.
OMAEMVKMGR.
OrthoDBEOG77126J.
PhylomeDBP13866.
TreeFamTF352855.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP13866.
BgeeP13866.
CleanExHS_SLC5A1.
GenevestigatorP13866.

Family and domain databases

InterProIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
IPR019900. Na/solute_symporter_subgr.
[Graphical view]
PANTHERPTHR11819. PTHR11819. 1 hit.
PfamPF00474. SSF. 1 hit.
[Graphical view]
TIGRFAMsTIGR00813. sss. 1 hit.
PROSITEPS00456. NA_SOLUT_SYMP_1. 1 hit.
PS00457. NA_SOLUT_SYMP_2. 1 hit.
PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSLC5A1.
GenomeRNAi6523.
NextBio25375.
PROP13866.
SOURCESearch...

Entry information

Entry nameSC5A1_HUMAN
AccessionPrimary (citable) accession number: P13866
Secondary accession number(s): B2R7E2, B7Z4Q9, B7ZA69
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: April 16, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM