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Protein

Sodium/glucose cotransporter 1

Gene

SLC5A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei43Implicated in sodium couplingBy similarity1
Sitei300Implicated in sodium couplingBy similarity1
Binding sitei457GlucoseBy similarity1
Sitei460Involved in sugar-binding/transport and inhibitor bindingBy similarity1

GO - Molecular functioni

  • glucose:sodium symporter activity Source: UniProtKB

GO - Biological processi

  • glucose transmembrane transport Source: UniProtKB
  • intestinal hexose absorption Source: Reactome
  • sodium ion transport Source: GO_Central

Keywordsi

Biological processIon transport, Sodium transport, Sugar transport, Symport, Transport
LigandSodium

Enzyme and pathway databases

ReactomeiR-HSA-189200 Cellular hexose transport
R-HSA-5656364 Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM)
R-HSA-8981373 Intestinal hexose absorption
SIGNORiP13866

Protein family/group databases

TCDBi2.A.21.3.1 the solute:sodium symporter (sss) family

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SLC5A1
Synonyms:NAGT, SGLT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100170.9
HGNCiHGNC:11036 SLC5A1
MIMi182380 gene
neXtProtiNX_P13866

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 28ExtracellularSequence analysisAdd BLAST28
Transmembranei29 – 49HelicalSequence analysisAdd BLAST21
Topological domaini50 – 64CytoplasmicSequence analysisAdd BLAST15
Transmembranei65 – 85HelicalSequence analysisAdd BLAST21
Topological domaini86 – 105ExtracellularSequence analysisAdd BLAST20
Transmembranei106 – 126HelicalSequence analysisAdd BLAST21
Topological domaini127 – 142CytoplasmicSequence analysisAdd BLAST16
Transmembranei143 – 163HelicalSequence analysisAdd BLAST21
Topological domaini164 – 178ExtracellularSequence analysisAdd BLAST15
Transmembranei179 – 201HelicalSequence analysisAdd BLAST23
Topological domaini202 – 208CytoplasmicSequence analysis7
Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
Topological domaini230 – 277ExtracellularSequence analysisAdd BLAST48
Transmembranei278 – 298HelicalSequence analysisAdd BLAST21
Topological domaini299 – 313CytoplasmicSequence analysisAdd BLAST15
Transmembranei314 – 334HelicalSequence analysisAdd BLAST21
Topological domaini335 – 380ExtracellularSequence analysisAdd BLAST46
Transmembranei381 – 401HelicalSequence analysisAdd BLAST21
Topological domaini402 – 423CytoplasmicSequence analysisAdd BLAST22
Transmembranei424 – 444HelicalSequence analysisAdd BLAST21
Topological domaini445 – 455ExtracellularSequence analysisAdd BLAST11
Transmembranei456 – 476HelicalSequence analysisAdd BLAST21
Topological domaini477 – 484CytoplasmicSequence analysis8
Transmembranei485 – 505HelicalSequence analysisAdd BLAST21
Topological domaini506 – 526ExtracellularSequence analysisAdd BLAST21
Intramembranei527 – 563HelicalSequence analysisAdd BLAST37
Topological domaini564 – 643ExtracellularSequence analysisAdd BLAST80
Transmembranei644 – 664HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital glucose/galactose malabsorption (GGM)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionIntestinal 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.
See also OMIM:606824
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01363028D → G in GGM. 1 PublicationCorresponds to variant dbSNP:rs121912669EnsemblClinVar.1
Natural variantiVAR_00716828D → N in GGM. 1 PublicationCorresponds to variant dbSNP:rs121912668EnsemblClinVar.1
Natural variantiVAR_021502135R → W in GGM; loss of activity. 1 Publication1
Natural variantiVAR_021503318G → R in GGM. 1 PublicationCorresponds to variant dbSNP:rs371505974Ensembl.1
Natural variantiVAR_021504468A → V in GGM. 1 PublicationCorresponds to variant dbSNP:rs200406921Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi248N → Q: Loss of N-glycosylation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6523
MalaCardsiSLC5A1
MIMi606824 phenotype
OpenTargetsiENSG00000100170
Orphaneti35710 Glucose-galactose malabsorption
PharmGKBiPA308

Chemistry databases

ChEMBLiCHEMBL4979
DrugBankiDB08907 Canagliflozin
GuidetoPHARMACOLOGYi915

Polymorphism and mutation databases

BioMutaiSLC5A1
DMDMi127803

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001053661 – 664Sodium/glucose cotransporter 1Add BLAST664

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi248N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi255 ↔ 610By similarity
Modified residuei587PhosphothreonineBy similarity1

Post-translational modificationi

N-glycosylation is not necessary for the cotransporter function.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP13866
MaxQBiP13866
PaxDbiP13866
PeptideAtlasiP13866
PRIDEiP13866
ProteomicsDBi52997

PTM databases

iPTMnetiP13866
PhosphoSitePlusiP13866

Expressioni

Tissue specificityi

Expressed mainly in intestine and kidney.

Gene expression databases

BgeeiENSG00000100170 Expressed in 111 organ(s), highest expression level in duodenum
CleanExiHS_SLC5A1
GenevisibleiP13866 HS

Organism-specific databases

HPAiCAB015467
HPA051805
HPA055106

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005333EBI-1772443,EBI-297353

Protein-protein interaction databases

BioGridi112414, 2 interactors
IntActiP13866, 1 interactor
STRINGi9606.ENSP00000266088

Chemistry databases

BindingDBiP13866

Structurei

3D structure databases

ProteinModelPortaliP13866
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IP49 Eukaryota
COG4146 LUCA
GeneTreeiENSGT00760000118955
HOVERGENiHBG052859
InParanoidiP13866
KOiK14158
OMAiCWTDLIQ
OrthoDBiEOG091G077U
PhylomeDBiP13866
TreeFamiTF352855

Family and domain databases

Gene3Di1.20.1730.10, 1 hit
InterProiView protein in InterPro
IPR038377 Na/Glc_symporter_sf
IPR001734 Na/solute_symporter
IPR018212 Na/solute_symporter_CS
PfamiView protein in Pfam
PF00474 SSF, 1 hit
TIGRFAMsiTIGR00813 sss, 1 hit
PROSITEiView protein in PROSITE
PS00456 NA_SOLUT_SYMP_1, 1 hit
PS00457 NA_SOLUT_SYMP_2, 1 hit
PS50283 NA_SOLUT_SYMP_3, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P13866-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDSSTWSPKT TAVTRPVETH ELIRNAADIS IIVIYFVVVM AVGLWAMFST
60 70 80 90 100
NRGTVGGFFL AGRSMVWWPI GASLFASNIG SGHFVGLAGT GAASGIAIGG
110 120 130 140 150
FEWNALVLVV VLGWLFVPIY IKAGVVTMPE YLRKRFGGQR IQVYLSLLSL
160 170 180 190 200
LLYIFTKISA DIFSGAIFIN LALGLNLYLA IFLLLAITAL YTITGGLAAV
210 220 230 240 250
IYTDTLQTVI MLVGSLILTG FAFHEVGGYD AFMEKYMKAI PTIVSDGNTT
260 270 280 290 300
FQEKCYTPRA DSFHIFRDPL TGDLPWPGFI FGMSILTLWY WCTDQVIVQR
310 320 330 340 350
CLSAKNMSHV KGGCILCGYL KLMPMFIMVM PGMISRILYT EKIACVVPSE
360 370 380 390 400
CEKYCGTKVG CTNIAYPTLV VELMPNGLRG LMLSVMLASL MSSLTSIFNS
410 420 430 440 450
ASTLFTMDIY AKVRKRASEK ELMIAGRLFI LVLIGISIAW VPIVQSAQSG
460 470 480 490 500
QLFDYIQSIT SYLGPPIAAV FLLAIFWKRV NEPGAFWGLI LGLLIGISRM
510 520 530 540 550
ITEFAYGTGS CMEPSNCPTI ICGVHYLYFA IILFAISFIT IVVISLLTKP
560 570 580 590 600
IPDVHLYRLC WSLRNSKEER IDLDAEEENI QEGPKETIEI ETQVPEKKKG
610 620 630 640 650
IFRRAYDLFC GLEQHGAPKM TEEEEKAMKM KMTDTSEKPL WRTVLNVNGI
660
ILVTVAVFCH AYFA
Length:664
Mass (Da):73,498
Last modified:January 1, 1990 - v1
Checksum:i2B403376595EAB74
GO
Isoform 2 (identifier: P13866-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-127: Missing.

Note: No experimental confirmation available.
Show »
Length:537
Mass (Da):60,097
Checksum:iF7B5A898E54C9476
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti631K → R in BAH14555 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01363028D → G in GGM. 1 PublicationCorresponds to variant dbSNP:rs121912669EnsemblClinVar.1
Natural variantiVAR_00716828D → N in GGM. 1 PublicationCorresponds to variant dbSNP:rs121912668EnsemblClinVar.1
Natural variantiVAR_02914751N → S. Corresponds to variant dbSNP:rs17683011EnsemblClinVar.1
Natural variantiVAR_021502135R → W in GGM; loss of activity. 1 Publication1
Natural variantiVAR_021503318G → R in GGM. 1 PublicationCorresponds to variant dbSNP:rs371505974Ensembl.1
Natural variantiVAR_029148411A → T. Corresponds to variant dbSNP:rs17683430EnsemblClinVar.1
Natural variantiVAR_021504468A → V in GGM. 1 PublicationCorresponds to variant dbSNP:rs200406921Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0447821 – 127Missing in isoform 2. 1 PublicationAdd BLAST127

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24847 mRNA Translation: AAA60320.1
L29339
, 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 Genomic DNA No translation available.
Z74021 Genomic DNA No translation available.
Z80998 Genomic DNA No translation available.
Z83839 Genomic DNA No translation available.
Z83849 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60006.1
CCDSiCCDS13902.1 [P13866-1]
CCDS58805.1 [P13866-2]
PIRiA33545
RefSeqiNP_000334.1, NM_000343.3 [P13866-1]
NP_001243243.1, NM_001256314.1 [P13866-2]
UniGeneiHs.1964

Genome annotation databases

EnsembliENST00000266088; ENSP00000266088; ENSG00000100170 [P13866-1]
ENST00000543737; ENSP00000444898; ENSG00000100170 [P13866-2]
GeneIDi6523
KEGGihsa:6523
UCSCiuc003amc.4 human [P13866-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24847 mRNA Translation: AAA60320.1
L29339
, 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 Genomic DNA No translation available.
Z74021 Genomic DNA No translation available.
Z80998 Genomic DNA No translation available.
Z83839 Genomic DNA No translation available.
Z83849 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60006.1
CCDSiCCDS13902.1 [P13866-1]
CCDS58805.1 [P13866-2]
PIRiA33545
RefSeqiNP_000334.1, NM_000343.3 [P13866-1]
NP_001243243.1, NM_001256314.1 [P13866-2]
UniGeneiHs.1964

3D structure databases

ProteinModelPortaliP13866
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112414, 2 interactors
IntActiP13866, 1 interactor
STRINGi9606.ENSP00000266088

Chemistry databases

BindingDBiP13866
ChEMBLiCHEMBL4979
DrugBankiDB08907 Canagliflozin
GuidetoPHARMACOLOGYi915

Protein family/group databases

TCDBi2.A.21.3.1 the solute:sodium symporter (sss) family

PTM databases

iPTMnetiP13866
PhosphoSitePlusiP13866

Polymorphism and mutation databases

BioMutaiSLC5A1
DMDMi127803

Proteomic databases

EPDiP13866
MaxQBiP13866
PaxDbiP13866
PeptideAtlasiP13866
PRIDEiP13866
ProteomicsDBi52997

Protocols and materials databases

DNASUi6523
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266088; ENSP00000266088; ENSG00000100170 [P13866-1]
ENST00000543737; ENSP00000444898; ENSG00000100170 [P13866-2]
GeneIDi6523
KEGGihsa:6523
UCSCiuc003amc.4 human [P13866-1]

Organism-specific databases

CTDi6523
DisGeNETi6523
EuPathDBiHostDB:ENSG00000100170.9
GeneCardsiSLC5A1
HGNCiHGNC:11036 SLC5A1
HPAiCAB015467
HPA051805
HPA055106
MalaCardsiSLC5A1
MIMi182380 gene
606824 phenotype
neXtProtiNX_P13866
OpenTargetsiENSG00000100170
Orphaneti35710 Glucose-galactose malabsorption
PharmGKBiPA308
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IP49 Eukaryota
COG4146 LUCA
GeneTreeiENSGT00760000118955
HOVERGENiHBG052859
InParanoidiP13866
KOiK14158
OMAiCWTDLIQ
OrthoDBiEOG091G077U
PhylomeDBiP13866
TreeFamiTF352855

Enzyme and pathway databases

ReactomeiR-HSA-189200 Cellular hexose transport
R-HSA-5656364 Defective SLC5A1 causes congenital glucose/galactose malabsorption (GGM)
R-HSA-8981373 Intestinal hexose absorption
SIGNORiP13866

Miscellaneous databases

ChiTaRSiSLC5A1 human
GeneWikiiSLC5A1
GenomeRNAii6523
PROiPR:P13866
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100170 Expressed in 111 organ(s), highest expression level in duodenum
CleanExiHS_SLC5A1
GenevisibleiP13866 HS

Family and domain databases

Gene3Di1.20.1730.10, 1 hit
InterProiView protein in InterPro
IPR038377 Na/Glc_symporter_sf
IPR001734 Na/solute_symporter
IPR018212 Na/solute_symporter_CS
PfamiView protein in Pfam
PF00474 SSF, 1 hit
TIGRFAMsiTIGR00813 sss, 1 hit
PROSITEiView protein in PROSITE
PS00456 NA_SOLUT_SYMP_1, 1 hit
PS00457 NA_SOLUT_SYMP_2, 1 hit
PS50283 NA_SOLUT_SYMP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSC5A1_HUMAN
AccessioniPrimary (citable) accession number: P13866
Secondary accession number(s): B2R7E2, B7Z4Q9, B7ZA69
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: November 7, 2018
This is version 190 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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