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Protein

Solute carrier family 2, facilitated glucose transporter member 4

Gene

SLC2A4

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

Functioni

Insulin-regulated facilitative glucose transporter.

Miscellaneous

Insulin-stimulated phosphorylation of TBC1D4 is required for GLUT4 translocation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei333MonosaccharideBy similarity1
Binding sitei404MonosaccharideBy similarity1

GO - Molecular functioni

  • D-glucose transmembrane transporter activity Source: Reactome
  • glucose transmembrane transporter activity Source: ProtInc

GO - Biological processi

  • amylopectin biosynthetic process Source: Ensembl
  • brown fat cell differentiation Source: Ensembl
  • carbohydrate metabolic process Source: ProtInc
  • cellular response to hypoxia Source: Ensembl
  • cellular response to insulin stimulus Source: UniProtKB
  • cellular response to osmotic stress Source: Ensembl
  • cellular response to tumor necrosis factor Source: Ensembl
  • glucose homeostasis Source: BHF-UCL
  • glucose import Source: BHF-UCL
  • glucose import in response to insulin stimulus Source: Ensembl
  • glucose transmembrane transport Source: UniProtKB
  • response to ethanol Source: Ensembl

Keywordsi

Biological processSugar transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-1445148 Translocation of GLUT4 to the plasma membrane
R-HSA-189200 Cellular hexose transport
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
SIGNORiP14672

Protein family/group databases

TCDBi2.A.1.1.80 the major facilitator superfamily (mfs)

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 2, facilitated glucose transporter member 4
Alternative name(s):
Glucose transporter type 4, insulin-responsive
Short name:
GLUT-4
Gene namesi
Name:SLC2A4
Synonyms:GLUT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000181856.14
HGNCiHGNC:11009 SLC2A4
MIMi138190 gene
neXtProtiNX_P14672

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 – 24CytoplasmicSequence analysisAdd BLAST24
Transmembranei25 – 45Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini46 – 81ExtracellularSequence analysisAdd BLAST36
Transmembranei82 – 102Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini103 – 111CytoplasmicSequence analysis9
Transmembranei112 – 132Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini133 – 142ExtracellularSequence analysis10
Transmembranei143 – 163Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini164 – 171CytoplasmicSequence analysis8
Transmembranei172 – 192Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini193 – 201ExtracellularSequence analysis9
Transmembranei202 – 222Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini223 – 287CytoplasmicSequence analysisAdd BLAST65
Transmembranei288 – 308Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini309 – 323ExtracellularSequence analysisAdd BLAST15
Transmembranei324 – 344Helical; Name=8Sequence analysisAdd BLAST21
Topological domaini345 – 353CytoplasmicSequence analysis9
Transmembranei354 – 374Helical; Name=9Sequence analysisAdd BLAST21
Topological domaini375 – 384ExtracellularSequence analysis10
Transmembranei385 – 405Helical; Name=10Sequence analysisAdd BLAST21
Topological domaini406 – 417CytoplasmicSequence analysisAdd BLAST12
Transmembranei418 – 438Helical; Name=11Sequence analysisAdd BLAST21
Topological domaini439 – 445ExtracellularSequence analysis7
Transmembranei446 – 466Helical; Name=12Sequence analysisAdd BLAST21
Topological domaini467 – 509CytoplasmicSequence analysisAdd BLAST43

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Diabetes mellitus, non-insulin-dependent (NIDDM)3 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:125853
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007170383V → I in NIDDM. 3 PublicationsCorresponds to variant dbSNP:rs121434581EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi489 – 490LL → AA: Changes subcellular location mainly to the plasma membrane. 1 Publication2

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi6517
MalaCardsiSLC2A4
MIMi125853 phenotype
OpenTargetsiENSG00000181856
PharmGKBiPA35879

Chemistry databases

ChEMBLiCHEMBL5874
DrugBankiDB09502 Fludeoxyglucose F-18

Polymorphism and mutation databases

BioMutaiSLC2A4
DMDMi121761

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000503631 – 509Solute carrier family 2, facilitated glucose transporter member 4Add BLAST509

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Glycosylationi57N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei274Phosphoserine; by SGK11 Publication1
Modified residuei486PhosphothreonineBy similarity1
Modified residuei488PhosphoserineBy similarity1

Post-translational modificationi

Sumoylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP14672
PaxDbiP14672
PeptideAtlasiP14672
PRIDEiP14672
ProteomicsDBi53073

PTM databases

iPTMnetiP14672
PhosphoSitePlusiP14672
SwissPalmiP14672

Expressioni

Tissue specificityi

Skeletal and cardiac muscles; brown and white fat.

Gene expression databases

BgeeiENSG00000181856
CleanExiHS_SLC2A4
ExpressionAtlasiP14672 baseline and differential
GenevisibleiP14672 HS

Organism-specific databases

HPAiCAB016544

Interactioni

Subunit structurei

Interacts with NDUFA9 (By similarity). Binds to DAXX. Interacts via its N-terminus with SRFBP1.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CREB3O43889-23EBI-367146,EBI-625022

Protein-protein interaction databases

BioGridi112408, 39 interactors
CORUMiP14672
IntActiP14672, 3 interactors
MINTiP14672
STRINGi9606.ENSP00000320935

Structurei

3D structure databases

ProteinModelPortaliP14672
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni7 – 13SRFBP1-binding7
Regioni298 – 304Monosaccharide bindingBy similarity7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi489 – 490Dileucine internalization motif2

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0569 Eukaryota
COG0477 LUCA
GeneTreeiENSGT00760000119022
HOGENOMiHOG000202871
HOVERGENiHBG014816
InParanoidiP14672
KOiK07191
OMAiNVYVVFF
OrthoDBiEOG091G0A9K
PhylomeDBiP14672
TreeFamiTF313762

Family and domain databases

CDDicd06174 MFS, 1 hit
InterProiView protein in InterPro
IPR002441 Glc_transpt_4
IPR020846 MFS_dom
IPR005828 MFS_sugar_transport-like
IPR036259 MFS_trans_sf
IPR003663 Sugar/inositol_transpt
IPR005829 Sugar_transporter_CS
PfamiView protein in Pfam
PF00083 Sugar_tr, 1 hit
PRINTSiPR01193 GLUCTRSPORT4
PR00171 SUGRTRNSPORT
SUPFAMiSSF103473 SSF103473, 1 hit
TIGRFAMsiTIGR00879 SP, 1 hit
PROSITEiView protein in PROSITE
PS50850 MFS, 1 hit
PS00216 SUGAR_TRANSPORT_1, 1 hit
PS00217 SUGAR_TRANSPORT_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P14672-1) [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
MPSGFQQIGS EDGEPPQQRV TGTLVLAVFS AVLGSLQFGY NIGVINAPQK
60 70 80 90 100
VIEQSYNETW LGRQGPEGPS SIPPGTLTTL WALSVAIFSV GGMISSFLIG
110 120 130 140 150
IISQWLGRKR AMLVNNVLAV LGGSLMGLAN AAASYEMLIL GRFLIGAYSG
160 170 180 190 200
LTSGLVPMYV GEIAPTHLRG ALGTLNQLAI VIGILIAQVL GLESLLGTAS
210 220 230 240 250
LWPLLLGLTV LPALLQLVLL PFCPESPRYL YIIQNLEGPA RKSLKRLTGW
260 270 280 290 300
ADVSGVLAEL KDEKRKLERE RPLSLLQLLG SRTHRQPLII AVVLQLSQQL
310 320 330 340 350
SGINAVFYYS TSIFETAGVG QPAYATIGAG VVNTVFTLVS VLLVERAGRR
360 370 380 390 400
TLHLLGLAGM CGCAILMTVA LLLLERVPAM SYVSIVAIFG FVAFFEIGPG
410 420 430 440 450
PIPWFIVAEL FSQGPRPAAM AVAGFSNWTS NFIIGMGFQY VAEAMGPYVF
460 470 480 490 500
LLFAVLLLGF FIFTFLRVPE TRGRTFDQIS AAFHRTPSLL EQEVKPSTEL

EYLGPDEND
Length:509
Mass (Da):54,787
Last modified:April 1, 1990 - v1
Checksum:i8E20CD97562C1EBF
GO
Isoform 2 (identifier: P14672-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     342-415: LLVERAGRRT...IVAELFSQGP → TAHLWNGPSH...CGHLWLRGIF
     416-509: Missing.

Note: No experimental confirmation available.
Show »
Length:415
Mass (Da):43,760
Checksum:iA46E00FD028AA5BE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti151 – 154Missing in AAA52569 (PubMed:1397719).Curated4

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05250355S → R. Corresponds to variant dbSNP:rs35198331Ensembl.1
Natural variantiVAR_01206078T → S. Corresponds to variant dbSNP:rs5434Ensembl.1
Natural variantiVAR_020336358A → V. Corresponds to variant dbSNP:rs8192702Ensembl.1
Natural variantiVAR_007170383V → I in NIDDM. 3 PublicationsCorresponds to variant dbSNP:rs121434581EnsemblClinVar.1
Natural variantiVAR_007171385I → T1 PublicationCorresponds to variant dbSNP:rs775242206Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056331342 – 415LLVER…FSQGP → TAHLWNGPSHWLHLPGCPGG VVGGAGGAPDAPSPGPGGHV WLCHPDDCGSAPAGASSSHE LRLHCGHLWLRGIF in isoform 2. 1 PublicationAdd BLAST74
Alternative sequenceiVSP_056332416 – 509Missing in isoform 2. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20747 mRNA Translation: AAA59189.1
M91463 Genomic DNA Translation: AAA52569.1
AC003688 Genomic DNA No translation available.
BC034387 mRNA Translation: AAH34387.1
BC069615 mRNA Translation: AAH69615.1
BC069621 mRNA Translation: AAH69621.1
BC113592 mRNA Translation: AAI13593.1
BC126164 mRNA Translation: AAI26165.1
X58489 Genomic DNA Translation: CAA41399.1
CCDSiCCDS11097.1 [P14672-1]
PIRiA49158 A33801
RefSeqiNP_001033.1, NM_001042.2 [P14672-1]
UniGeneiHs.380691

Genome annotation databases

EnsembliENST00000317370; ENSP00000320935; ENSG00000181856 [P14672-1]
ENST00000572485; ENSP00000461086; ENSG00000181856 [P14672-2]
GeneIDi6517
KEGGihsa:6517
UCSCiuc002gfp.4 human [P14672-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGTR4_HUMAN
AccessioniPrimary (citable) accession number: P14672
Secondary accession number(s): Q05BQ3, Q14CX2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: June 20, 2018
This is version 208 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. Human chromosome 17
    Human chromosome 17: 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

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