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Protein

Sodium/glucose cotransporter 2

Gene

SLC5A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sodium-dependent glucose transporter. Has a Na+ to glucose coupling ratio of 1:1.
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
Sitei40Implicated in sodium couplingBy similarity1
Sitei300Implicated in sodium couplingBy similarity1

GO - Molecular functioni

  • glucose:sodium symporter activity Source: Reactome
  • low-affinity glucose:sodium symporter activity Source: ProtInc

GO - Biological processi

  • carbohydrate metabolic process Source: ProtInc
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ion transport, Sodium transport, Sugar transport, Symport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140675-MONOMER.
ReactomeiR-HSA-189200. Hexose transport.
R-HSA-428808. Na+-dependent glucose transporters.
R-HSA-429593. Inositol transporters.
SIGNORiP31639.

Protein family/group databases

TCDBi2.A.21.3.16. the solute:sodium symporter (sss) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/glucose cotransporter 2
Short name:
Na(+)/glucose cotransporter 2
Alternative name(s):
Low affinity sodium-glucose cotransporter
Solute carrier family 5 member 2
Gene namesi
Name:SLC5A2
Synonyms:SGLT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11037. SLC5A2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 25CytoplasmicSequence analysisAdd BLAST25
Transmembranei26 – 44HelicalSequence analysisAdd BLAST19
Topological domaini45 – 61ExtracellularSequence analysisAdd BLAST17
Transmembranei62 – 82HelicalSequence analysisAdd BLAST21
Topological domaini83 – 102CytoplasmicSequence analysisAdd BLAST20
Transmembranei103 – 123HelicalSequence analysisAdd BLAST21
Topological domaini124 – 168ExtracellularSequence analysisAdd BLAST45
Transmembranei169 – 188HelicalSequence analysisAdd BLAST20
Topological domaini189 – 205CytoplasmicSequence analysisAdd BLAST17
Transmembranei206 – 226HelicalSequence analysisAdd BLAST21
Topological domaini227 – 270ExtracellularSequence analysisAdd BLAST44
Transmembranei271 – 291HelicalSequence analysisAdd BLAST21
Topological domaini292 – 314CytoplasmicSequence analysisAdd BLAST23
Transmembranei315 – 334HelicalSequence analysisAdd BLAST20
Topological domaini335 – 423ExtracellularSequence analysisAdd BLAST89
Transmembranei424 – 443HelicalSequence analysisAdd BLAST20
Topological domaini444 – 455CytoplasmicSequence analysisAdd BLAST12
Transmembranei456 – 476HelicalSequence analysisAdd BLAST21
Topological domaini477 – 526ExtracellularSequence analysisAdd BLAST50
Transmembranei527 – 547HelicalSequence analysisAdd BLAST21
Topological domaini548 – 650CytoplasmicSequence analysisAdd BLAST103
Transmembranei651 – 671HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: ProtInc
  • integral component of plasma membrane Source: GO_Central
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Renal glucosuria (GLYS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by persistent isolated glucosuria, normal fasting serum glucose concentration, decreased renal tubular resorption of glucose from the urine, and absence of any other signs of tubular dysfunction.
See also OMIM:233100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019310654N → S in GLYS. 1 PublicationCorresponds to variant rs61742739dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6524.
MalaCardsiSLC5A2.
MIMi233100. phenotype.
OpenTargetsiENSG00000140675.
Orphaneti69076. Renal glucosuria.
PharmGKBiPA35902.

Chemistry databases

ChEMBLiCHEMBL3884.
DrugBankiDB08907. Canagliflozin.
DB06292. Dapagliflozin.
DB09038. Empagliflozin.
GuidetoPHARMACOLOGYi916.

Polymorphism and mutation databases

BioMutaiSLC5A2.
DMDMi400337.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001053721 – 672Sodium/glucose cotransporter 2Add BLAST672

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi250N-linked (GlcNAc...)Sequence analysis1
Glycosylationi399N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP31639.
PeptideAtlasiP31639.
PRIDEiP31639.

PTM databases

iPTMnetiP31639.
PhosphoSitePlusiP31639.

Expressioni

Gene expression databases

BgeeiENSG00000140675.
CleanExiHS_SLC5A2.
ExpressionAtlasiP31639. baseline and differential.
GenevisibleiP31639. HS.

Organism-specific databases

HPAiHPA041603.

Interactioni

Protein-protein interaction databases

BioGridi112415. 1 interactor.
STRINGi9606.ENSP00000327943.

Chemistry databases

BindingDBiP31639.

Structurei

3D structure databases

ProteinModelPortaliP31639.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IP49. Eukaryota.
COG4146. LUCA.
GeneTreeiENSGT00760000118955.
HOGENOMiHOG000025422.
HOVERGENiHBG052859.
InParanoidiP31639.
KOiK14382.
OMAiCTAPIPR.
OrthoDBiEOG091G077U.
PhylomeDBiP31639.
TreeFamiTF352855.

Family and domain databases

InterProiIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
[Graphical view]
PANTHERiPTHR11819. PTHR11819. 2 hits.
PfamiPF00474. SSF. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00813. sss. 1 hit.
PROSITEiPS00456. NA_SOLUT_SYMP_1. 1 hit.
PS00457. NA_SOLUT_SYMP_2. 1 hit.
PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P31639-1) [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
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
Length:672
Mass (Da):72,897
Last modified:July 1, 1993 - v1
Checksum:i233C65F1601B0337
GO
Isoform 2 (identifier: P31639-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     378-458: LRGLMLAVML...GGQLFDYIQA → RLLGTHRGPA...PPPPGLQSPA
     459-672: Missing.

Note: No experimental confirmation available.
Show »
Length:458
Mass (Da):49,357
Checksum:iB8FE8FA645AA481A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019310654N → S in GLYS. 1 PublicationCorresponds to variant rs61742739dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056333378 – 458LRGLM…DYIQA → RLLGTHRGPADGPGTPDSRV LLRLGQLCAALGVPSFPLRR ALPLLRHCAVLLLWPPHPHG LPVHRAHPQKAPPPPGLQSP A in isoform 2. 1 PublicationAdd BLAST81
Alternative sequenceiVSP_056334459 – 672Missing in isoform 2. 1 PublicationAdd BLAST214

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.
CCDSiCCDS10714.1. [P31639-1]
PIRiA56765.
RefSeqiNP_003032.1. NM_003041.3. [P31639-1]
UniGeneiHs.709195.

Genome annotation databases

EnsembliENST00000330498; ENSP00000327943; ENSG00000140675. [P31639-1]
ENST00000419665; ENSP00000410601; ENSG00000140675. [P31639-2]
GeneIDi6524.
KEGGihsa:6524.
UCSCiuc002ecf.5. human. [P31639-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS10714.1. [P31639-1]
PIRiA56765.
RefSeqiNP_003032.1. NM_003041.3. [P31639-1]
UniGeneiHs.709195.

3D structure databases

ProteinModelPortaliP31639.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112415. 1 interactor.
STRINGi9606.ENSP00000327943.

Chemistry databases

BindingDBiP31639.
ChEMBLiCHEMBL3884.
DrugBankiDB08907. Canagliflozin.
DB06292. Dapagliflozin.
DB09038. Empagliflozin.
GuidetoPHARMACOLOGYi916.

Protein family/group databases

TCDBi2.A.21.3.16. the solute:sodium symporter (sss) family.

PTM databases

iPTMnetiP31639.
PhosphoSitePlusiP31639.

Polymorphism and mutation databases

BioMutaiSLC5A2.
DMDMi400337.

Proteomic databases

PaxDbiP31639.
PeptideAtlasiP31639.
PRIDEiP31639.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330498; ENSP00000327943; ENSG00000140675. [P31639-1]
ENST00000419665; ENSP00000410601; ENSG00000140675. [P31639-2]
GeneIDi6524.
KEGGihsa:6524.
UCSCiuc002ecf.5. human. [P31639-1]

Organism-specific databases

CTDi6524.
DisGeNETi6524.
GeneCardsiSLC5A2.
HGNCiHGNC:11037. SLC5A2.
HPAiHPA041603.
MalaCardsiSLC5A2.
MIMi182381. gene.
233100. phenotype.
neXtProtiNX_P31639.
OpenTargetsiENSG00000140675.
Orphaneti69076. Renal glucosuria.
PharmGKBiPA35902.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IP49. Eukaryota.
COG4146. LUCA.
GeneTreeiENSGT00760000118955.
HOGENOMiHOG000025422.
HOVERGENiHBG052859.
InParanoidiP31639.
KOiK14382.
OMAiCTAPIPR.
OrthoDBiEOG091G077U.
PhylomeDBiP31639.
TreeFamiTF352855.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140675-MONOMER.
ReactomeiR-HSA-189200. Hexose transport.
R-HSA-428808. Na+-dependent glucose transporters.
R-HSA-429593. Inositol transporters.
SIGNORiP31639.

Miscellaneous databases

ChiTaRSiSLC5A2. human.
GeneWikiiSLC5A2.
GenomeRNAii6524.
PROiP31639.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140675.
CleanExiHS_SLC5A2.
ExpressionAtlasiP31639. baseline and differential.
GenevisibleiP31639. HS.

Family and domain databases

InterProiIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
[Graphical view]
PANTHERiPTHR11819. PTHR11819. 2 hits.
PfamiPF00474. SSF. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00813. sss. 1 hit.
PROSITEiPS00456. NA_SOLUT_SYMP_1. 1 hit.
PS00457. NA_SOLUT_SYMP_2. 1 hit.
PS50283. NA_SOLUT_SYMP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSC5A2_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 153 of the entry and version 1 of the sequence. [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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.