UniProtKB - P31639 (SC5A2_HUMAN)
Sodium/glucose cotransporter 2
SLC5A2
Functioni
Electrogenic Na+-coupled sugar simporter that actively transports D-glucose at the plasma membrane, with a Na+ to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na+ electrochemical gradient set by the Na+/K+ pump (PubMed:20980548, PubMed:28592437, PubMed:34880493).
Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).
By similarity3 PublicationsCatalytic activityi
- This reaction proceeds in the forward3 Publications direction.
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 40 | Implicated in sodium couplingBy similarity | 1 | |
Sitei | 300 | Implicated in sodium couplingBy similarity | 1 |
GO - Molecular functioni
- alpha-glucoside transmembrane transporter activity Source: ARUK-UCL
- D-glucose transmembrane transporter activity Source: ARUK-UCL
- glucose:sodium symporter activity Source: ARUK-UCL
- low-affinity glucose:sodium symporter activity Source: ProtInc
GO - Biological processi
- alpha-glucoside transport Source: ARUK-UCL
- carbohydrate metabolic process Source: ProtInc
- glucose import across plasma membrane Source: ARUK-UCL
- hexose transmembrane transport Source: Reactome
- sodium ion import across plasma membrane Source: ARUK-UCL
- sodium ion transport Source: GO_Central
Keywordsi
Biological process | Ion transport, Sodium transport, Sugar transport, Symport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | P31639 |
Reactomei | R-HSA-189200, Cellular hexose transport R-HSA-5658208, Defective SLC5A2 causes renal glucosuria (GLYS1) |
SABIO-RKi | P31639 |
SignaLinki | P31639 |
SIGNORi | P31639 |
Protein family/group databases
TCDBi | 2.A.1.7.26, the major facilitator superfamily (mfs) 2.A.21.3.16, the solute:sodium symporter (sss) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium/glucose cotransporter 2Short name: Na(+)/glucose cotransporter 2 Alternative name(s): Low affinity sodium-glucose cotransporter Solute carrier family 5 member 2 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11037, SLC5A2 |
MIMi | 182381, gene |
neXtProti | NX_P31639 |
VEuPathDBi | HostDB:ENSG00000140675 |
Subcellular locationi
Plasma membrane
- Apical cell membrane By similarity; Multi-pass membrane protein Sequence analysis
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- plasma membrane Source: ARUK-UCL
Other locations
- integral component of membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 25 | CytoplasmicSequence analysisAdd BLAST | 25 | |
Transmembranei | 26 – 44 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 45 – 61 | ExtracellularSequence analysisAdd BLAST | 17 | |
Transmembranei | 62 – 82 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 83 – 102 | CytoplasmicSequence analysisAdd BLAST | 20 | |
Transmembranei | 103 – 123 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 124 – 168 | ExtracellularSequence analysisAdd BLAST | 45 | |
Transmembranei | 169 – 188 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 189 – 205 | CytoplasmicSequence analysisAdd BLAST | 17 | |
Transmembranei | 206 – 226 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 227 – 270 | ExtracellularSequence analysisAdd BLAST | 44 | |
Transmembranei | 271 – 291 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 292 – 314 | CytoplasmicSequence analysisAdd BLAST | 23 | |
Transmembranei | 315 – 334 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 335 – 423 | ExtracellularSequence analysisAdd BLAST | 89 | |
Transmembranei | 424 – 443 | HelicalSequence analysisAdd BLAST | 20 | |
Topological domaini | 444 – 455 | CytoplasmicSequence analysisAdd BLAST | 12 | |
Transmembranei | 456 – 476 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 477 – 526 | ExtracellularSequence analysisAdd BLAST | 50 | |
Transmembranei | 527 – 547 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 548 – 650 | CytoplasmicSequence analysisAdd BLAST | 103 | |
Transmembranei | 651 – 671 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Renal glucosuria (GLYS)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019310 | 654 | N → S in GLYS. 1 PublicationCorresponds to variant dbSNP:rs61742739EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 95 | V → A: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition. 1 Publication | 1 | |
Mutagenesisi | 98 | F → A: Slightly decreases D-glucose transporter activity. Abolishes the binding to inhibitor, empagliflozin. 1 Publication | 1 | |
Mutagenesisi | 157 | V → A: Decreases D-glucose transporter activity. 1 Publication | 1 | |
Mutagenesisi | 283 | L → M: Strong reduction in D-glucose transporter activity. Confers partial resistance to empagliflozin inhibition. 1 Publication | 1 | |
Mutagenesisi | 453 | F → A: Slightly decreases D-glucose transporter activity. Greatly reduces the binding to inhibitor, empagliflozin. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 6524 |
MalaCardsi | SLC5A2 |
MIMi | 233100, phenotype |
OpenTargetsi | ENSG00000140675 |
Orphaneti | 69076, Familial renal glucosuria |
PharmGKBi | PA35902 |
Miscellaneous databases
Pharosi | P31639, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3884 |
DrugBanki | DB08907, Canagliflozin DB01914, D-glucose DB06292, Dapagliflozin DB09038, Empagliflozin DB11827, Ertugliflozin |
DrugCentrali | P31639 |
GuidetoPHARMACOLOGYi | 916 |
Genetic variation databases
BioMutai | SLC5A2 |
DMDMi | 400337 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000105372 | 1 – 672 | Sodium/glucose cotransporter 2Add BLAST | 672 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 250 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 399 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | P31639 |
MassIVEi | P31639 |
PaxDbi | P31639 |
PeptideAtlasi | P31639 |
PRIDEi | P31639 |
ProteomicsDBi | 461 54795 [P31639-1] |
PTM databases
CarbonylDBi | P31639 |
GlyGeni | P31639, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | P31639 |
PhosphoSitePlusi | P31639 |
Expressioni
Gene expression databases
Bgeei | ENSG00000140675, Expressed in adult mammalian kidney and 142 other tissues |
ExpressionAtlasi | P31639, baseline and differential |
Genevisiblei | P31639, HS |
Organism-specific databases
HPAi | ENSG00000140675, Tissue enriched (kidney) |
Interactioni
Subunit structurei
Forms a heterodimer with PDZK1IP1; this interaction enhances the transporter activity over a hundred-fold.
1 PublicationProtein-protein interaction databases
BioGRIDi | 112415, 13 interactors |
IntActi | P31639, 4 interactors |
MINTi | P31639 |
STRINGi | 9606.ENSP00000327943 |
Chemistry databases
BindingDBi | P31639 |
Miscellaneous databases
RNActi | P31639, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2349, Eukaryota |
GeneTreei | ENSGT00940000160533 |
HOGENOMi | CLU_018808_9_0_1 |
InParanoidi | P31639 |
OMAi | LEYWMAV |
PhylomeDBi | P31639 |
TreeFami | TF352855 |
Family and domain databases
Gene3Di | 1.20.1730.10, 1 hit |
InterProi | View protein in InterPro IPR038377, Na/Glc_symporter_sf IPR001734, Na/solute_symporter IPR018212, Na/solute_symporter_CS |
Pfami | View protein in Pfam PF00474, SSF, 1 hit |
TIGRFAMsi | TIGR00813, sss, 1 hit |
PROSITEi | View protein in PROSITE PS00456, NA_SOLUT_SYMP_1, 1 hit PS00457, NA_SOLUT_SYMP_2, 1 hit PS50283, NA_SOLUT_SYMP_3, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MEEHTEAGSA PEMGAQKALI DNPADILVIA AYFLLVIGVG LWSMCRTNRG
60 70 80 90 100
TVGGYFLAGR SMVWWPVGAS LFASNIGSGH FVGLAGTGAA SGLAVAGFEW
110 120 130 140 150
NALFVVLLLG WLFAPVYLTA GVITMPQYLR KRFGGRRIRL YLSVLSLFLY
160 170 180 190 200
IFTKISVDMF SGAVFIQQAL GWNIYASVIA LLGITMIYTV TGGLAALMYT
210 220 230 240 250
DTVQTFVILG GACILMGYAF HEVGGYSGLF DKYLGAATSL TVSEDPAVGN
260 270 280 290 300
ISSFCYRPRP DSYHLLRHPV TGDLPWPALL LGLTIVSGWY WCSDQVIVQR
310 320 330 340 350
CLAGKSLTHI KAGCILCGYL KLTPMFLMVM PGMISRILYP DEVACVVPEV
360 370 380 390 400
CRRVCGTEVG CSNIAYPRLV VKLMPNGLRG LMLAVMLAAL MSSLASIFNS
410 420 430 440 450
SSTLFTMDIY TRLRPRAGDR ELLLVGRLWV VFIVVVSVAW LPVVQAAQGG
460 470 480 490 500
QLFDYIQAVS SYLAPPVSAV FVLALFVPRV NEQGAFWGLI GGLLMGLARL
510 520 530 540 550
IPEFSFGSGS CVQPSACPAF LCGVHYLYFA IVLFFCSGLL TLTVSLCTAP
560 570 580 590 600
IPRKHLHRLV FSLRHSKEER EDLDADEQQG SSLPVQNGCP ESAMEMNEPQ
610 620 630 640 650
APAPSLFRQC LLWFCGMSRG GVGSPPPLTQ EEAAAAARRL EDISEDPSWA
660 670
RVVNLNALLM MAVAVFLWGF YA
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH3BP44 | H3BP44_HUMAN | Sodium/glucose cotransporter 2 | SLC5A2 | 148 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019310 | 654 | N → S in GLYS. 1 PublicationCorresponds to variant dbSNP:rs61742739EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056333 | 378 – 458 | LRGLM…DYIQA → RLLGTHRGPADGPGTPDSRV LLRLGQLCAALGVPSFPLRR ALPLLRHCAVLLLWPPHPHG LPVHRAHPQKAPPPPGLQSP A in isoform 2. 1 PublicationAdd BLAST | 81 | |
Alternative sequenceiVSP_056334 | 459 – 672 | Missing in isoform 2. 1 PublicationAdd BLAST | 214 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M95549 mRNA Translation: AAA36608.1 AC026471 Genomic DNA No translation available. BC131542 mRNA Translation: AAI31543.1 |
CCDSi | CCDS10714.1 [P31639-1] |
PIRi | A56765 |
RefSeqi | NP_003032.1, NM_003041.3 [P31639-1] |
Genome annotation databases
Ensembli | ENST00000330498.4; ENSP00000327943.3; ENSG00000140675.13 ENST00000419665.6; ENSP00000410601.2; ENSG00000140675.13 [P31639-2] |
GeneIDi | 6524 |
KEGGi | hsa:6524 |
MANE-Selecti | ENST00000330498.4; ENSP00000327943.3; NM_003041.4; NP_003032.1 |
UCSCi | uc002ecf.5, human [P31639-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M95549 mRNA Translation: AAA36608.1 AC026471 Genomic DNA No translation available. BC131542 mRNA Translation: AAI31543.1 |
CCDSi | CCDS10714.1 [P31639-1] |
PIRi | A56765 |
RefSeqi | NP_003032.1, NM_003041.3 [P31639-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
7VSI | electron microscopy | 2.95 | A | 1-672 | [»] | |
AlphaFoldDBi | P31639 | |||||
SMRi | P31639 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112415, 13 interactors |
IntActi | P31639, 4 interactors |
MINTi | P31639 |
STRINGi | 9606.ENSP00000327943 |
Chemistry databases
BindingDBi | P31639 |
ChEMBLi | CHEMBL3884 |
DrugBanki | DB08907, Canagliflozin DB01914, D-glucose DB06292, Dapagliflozin DB09038, Empagliflozin DB11827, Ertugliflozin |
DrugCentrali | P31639 |
GuidetoPHARMACOLOGYi | 916 |
Protein family/group databases
TCDBi | 2.A.1.7.26, the major facilitator superfamily (mfs) 2.A.21.3.16, the solute:sodium symporter (sss) family |
PTM databases
CarbonylDBi | P31639 |
GlyGeni | P31639, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | P31639 |
PhosphoSitePlusi | P31639 |
Genetic variation databases
BioMutai | SLC5A2 |
DMDMi | 400337 |
Proteomic databases
jPOSTi | P31639 |
MassIVEi | P31639 |
PaxDbi | P31639 |
PeptideAtlasi | P31639 |
PRIDEi | P31639 |
ProteomicsDBi | 461 54795 [P31639-1] |
Protocols and materials databases
Antibodypediai | 27902, 211 antibodies from 32 providers |
DNASUi | 6524 |
Genome annotation databases
Ensembli | ENST00000330498.4; ENSP00000327943.3; ENSG00000140675.13 ENST00000419665.6; ENSP00000410601.2; ENSG00000140675.13 [P31639-2] |
GeneIDi | 6524 |
KEGGi | hsa:6524 |
MANE-Selecti | ENST00000330498.4; ENSP00000327943.3; NM_003041.4; NP_003032.1 |
UCSCi | uc002ecf.5, human [P31639-1] |
Organism-specific databases
CTDi | 6524 |
DisGeNETi | 6524 |
GeneCardsi | SLC5A2 |
HGNCi | HGNC:11037, SLC5A2 |
HPAi | ENSG00000140675, Tissue enriched (kidney) |
MalaCardsi | SLC5A2 |
MIMi | 182381, gene 233100, phenotype |
neXtProti | NX_P31639 |
OpenTargetsi | ENSG00000140675 |
Orphaneti | 69076, Familial renal glucosuria |
PharmGKBi | PA35902 |
VEuPathDBi | HostDB:ENSG00000140675 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2349, Eukaryota |
GeneTreei | ENSGT00940000160533 |
HOGENOMi | CLU_018808_9_0_1 |
InParanoidi | P31639 |
OMAi | LEYWMAV |
PhylomeDBi | P31639 |
TreeFami | TF352855 |
Enzyme and pathway databases
PathwayCommonsi | P31639 |
Reactomei | R-HSA-189200, Cellular hexose transport R-HSA-5658208, Defective SLC5A2 causes renal glucosuria (GLYS1) |
SABIO-RKi | P31639 |
SignaLinki | P31639 |
SIGNORi | P31639 |
Miscellaneous databases
BioGRID-ORCSi | 6524, 6 hits in 1058 CRISPR screens |
ChiTaRSi | SLC5A2, human |
GeneWikii | SLC5A2 |
GenomeRNAii | 6524 |
Pharosi | P31639, Tclin |
PROi | PR:P31639 |
RNActi | P31639, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000140675, Expressed in adult mammalian kidney and 142 other tissues |
ExpressionAtlasi | P31639, baseline and differential |
Genevisiblei | P31639, HS |
Family and domain databases
Gene3Di | 1.20.1730.10, 1 hit |
InterProi | View protein in InterPro IPR038377, Na/Glc_symporter_sf IPR001734, Na/solute_symporter IPR018212, Na/solute_symporter_CS |
Pfami | View protein in Pfam PF00474, SSF, 1 hit |
TIGRFAMsi | TIGR00813, sss, 1 hit |
PROSITEi | View protein in PROSITE PS00456, NA_SOLUT_SYMP_1, 1 hit PS00457, NA_SOLUT_SYMP_2, 1 hit PS50283, NA_SOLUT_SYMP_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SC5A2_HUMAN | |
Accessioni | P31639Primary (citable) accession number: P31639 Secondary accession number(s): A2RRD2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1993 |
Last sequence update: | July 1, 1993 | |
Last modified: | May 25, 2022 | |
This is version 188 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families