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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei40 – 401Implicated in sodium couplingBy similarity
Sitei300 – 3001Implicated in sodium couplingBy similarity

GO - Molecular functioni

  1. low-affinity glucose:sodium symporter activity Source: ProtInc

GO - Biological processi

  1. carbohydrate metabolic process Source: ProtInc
  2. glucose transport Source: GOC
  3. transmembrane transport Source: Reactome
  4. transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

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

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiREACT_19165. Na+-dependent glucose transporters.
REACT_19188. Inositol transporters.
REACT_268444. Orphan transporters.
REACT_9441. Hexose transport.

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
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11037. SLC5A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2525CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei26 – 4419HelicalSequence AnalysisAdd
BLAST
Topological domaini45 – 6117ExtracellularSequence AnalysisAdd
BLAST
Transmembranei62 – 8221HelicalSequence AnalysisAdd
BLAST
Topological domaini83 – 10220CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei103 – 12321HelicalSequence AnalysisAdd
BLAST
Topological domaini124 – 16845ExtracellularSequence AnalysisAdd
BLAST
Transmembranei169 – 18820HelicalSequence AnalysisAdd
BLAST
Topological domaini189 – 20517CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei206 – 22621HelicalSequence AnalysisAdd
BLAST
Topological domaini227 – 27044ExtracellularSequence AnalysisAdd
BLAST
Transmembranei271 – 29121HelicalSequence AnalysisAdd
BLAST
Topological domaini292 – 31423CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei315 – 33420HelicalSequence AnalysisAdd
BLAST
Topological domaini335 – 42389ExtracellularSequence AnalysisAdd
BLAST
Transmembranei424 – 44320HelicalSequence AnalysisAdd
BLAST
Topological domaini444 – 45512CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei456 – 47621HelicalSequence AnalysisAdd
BLAST
Topological domaini477 – 52650ExtracellularSequence AnalysisAdd
BLAST
Transmembranei527 – 54721HelicalSequence AnalysisAdd
BLAST
Topological domaini548 – 650103CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei651 – 67121HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProtKB
  2. integral component of membrane Source: ProtInc
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Renal glucosuria (GLYS1)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAutosomal recessive disorder characterized by a normal fasting serum glucose concentration and persistent isolated glucosuria, with a normal glucose tolerance test.

See also OMIM:233100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti654 – 6541N → S in GLYS1. 1 Publication
Corresponds to variant rs61742739 [ dbSNP | Ensembl ].
VAR_019310

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi233100. phenotype.
Orphaneti69076. Renal glucosuria.
PharmGKBiPA35902.

Chemistry

DrugBankiDB08907. Canagliflozin.
DB06292. Dapagliflozin.

Polymorphism and mutation databases

BioMutaiSLC5A2.
DMDMi400337.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 672672Sodium/glucose cotransporter 2PRO_0000105372Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi250 – 2501N-linked (GlcNAc...)Sequence Analysis
Glycosylationi399 – 3991N-linked (GlcNAc...)Sequence Analysis
Modified residuei592 – 5921PhosphoserineBy similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP31639.
PRIDEiP31639.

PTM databases

PhosphoSiteiP31639.

Expressioni

Gene expression databases

BgeeiP31639.
CleanExiHS_SLC5A2.
ExpressionAtlasiP31639. baseline and differential.
GenevestigatoriP31639.

Organism-specific databases

HPAiHPA041603.

Interactioni

Protein-protein interaction databases

BioGridi112415. 1 interaction.
STRINGi9606.ENSP00000327943.

Structurei

3D structure databases

ProteinModelPortaliP31639.
SMRiP31639. Positions 25-497.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG4146.
GeneTreeiENSGT00760000118955.
HOGENOMiHOG000025422.
HOVERGENiHBG052859.
InParanoidiP31639.
KOiK14382.
OMAiILMLGMH.
OrthoDBiEOG77126J.
PhylomeDBiP31639.
TreeFamiTF352855.

Family and domain databases

InterProiIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
IPR019900. Na/solute_symporter_subgr.
[Graphical view]
PANTHERiPTHR11819. PTHR11819. 1 hit.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti654 – 6541N → S in GLYS1. 1 Publication
Corresponds to variant rs61742739 [ dbSNP | Ensembl ].
VAR_019310

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei378 – 45881LRGLM…DYIQA → RLLGTHRGPADGPGTPDSRV LLRLGQLCAALGVPSFPLRR ALPLLRHCAVLLLWPPHPHG LPVHRAHPQKAPPPPGLQSP A in isoform 2. 1 PublicationVSP_056333Add
BLAST
Alternative sequencei459 – 672214Missing in isoform 2. 1 PublicationVSP_056334Add
BLAST

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.4. human. [P31639-1]

Polymorphism and mutation databases

BioMutaiSLC5A2.

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.
SMRiP31639. Positions 25-497.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112415. 1 interaction.
STRINGi9606.ENSP00000327943.

Chemistry

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

Protein family/group databases

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

PTM databases

PhosphoSiteiP31639.

Polymorphism and mutation databases

BioMutaiSLC5A2.
DMDMi400337.

Proteomic databases

PaxDbiP31639.
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.4. human. [P31639-1]

Organism-specific databases

CTDi6524.
GeneCardsiGC16P031494.
HGNCiHGNC:11037. SLC5A2.
HPAiHPA041603.
MIMi182381. gene.
233100. phenotype.
neXtProtiNX_P31639.
Orphaneti69076. Renal glucosuria.
PharmGKBiPA35902.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG4146.
GeneTreeiENSGT00760000118955.
HOGENOMiHOG000025422.
HOVERGENiHBG052859.
InParanoidiP31639.
KOiK14382.
OMAiILMLGMH.
OrthoDBiEOG77126J.
PhylomeDBiP31639.
TreeFamiTF352855.

Enzyme and pathway databases

ReactomeiREACT_19165. Na+-dependent glucose transporters.
REACT_19188. Inositol transporters.
REACT_268444. Orphan transporters.
REACT_9441. Hexose transport.

Miscellaneous databases

ChiTaRSiSLC5A2. human.
GeneWikiiSLC5A2.
GenomeRNAii6524.
NextBioi25379.
PROiP31639.
SOURCEiSearch...

Gene expression databases

BgeeiP31639.
CleanExiHS_SLC5A2.
ExpressionAtlasiP31639. baseline and differential.
GenevestigatoriP31639.

Family and domain databases

InterProiIPR001734. Na/solute_symporter.
IPR018212. Na/solute_symporter_CS.
IPR019900. Na/solute_symporter_subgr.
[Graphical view]
PANTHERiPTHR11819. PTHR11819. 1 hit.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter."
    Wells R.G., Pajor A.M., Kanai Y., Turk E., Wright E.M., Hediger M.A.
    Am. J. Physiol. 263:F459-F465(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Kidney.
  2. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  4. "Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria."
    Calado J., Soto K., Clemente C., Correia P., Rueff J.
    Hum. Genet. 114:314-316(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLYS1 SER-654.

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: April 29, 2015
This is version 138 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

External Data

Dasty 3

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 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.