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Protein

Solute carrier family 2, facilitated glucose transporter member 4

Gene

SLC2A4

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

Functioni

Insulin-regulated facilitative glucose transporter.

Sites

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

GO - Molecular functioni

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 transport Source: UniProtKB
  • response to ethanol Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Sugar transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000181856-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-428790. Facilitative Na+-independent glucose transporters.
R-HSA-70153. Glucose transport.
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

HGNCiHGNC:11009. SLC2A4.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Endomembrane system 1 Publication; Multi-pass membrane protein 1 Publication
  • Cytoplasmperinuclear region 1 Publication

  • Note: Localizes primarily to the perinuclear region, undergoing continued recycling to the plasma membrane where it is rapidly reinternalized. The dileucine internalization motif is critical for intracellular sequestration.

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

GO - Cellular componenti

  • clathrin-coated pit Source: Ensembl
  • clathrin-coated vesicle Source: UniProtKB
  • cytoplasmic vesicle membrane Source: Ensembl
  • cytosol Source: Ensembl
  • endomembrane system Source: UniProtKB
  • external side of plasma membrane Source: MGI
  • extracellular exosome Source: Ensembl
  • insulin-responsive compartment Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: ProtInc
  • membrane raft Source: Ensembl
  • multivesicular body Source: Ensembl
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • trans-Golgi network transport vesicle Source: Ensembl
  • T-tubule Source: Ensembl
  • vesicle membrane Source: MGI
Complete GO annotation...

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 rs121434581dbSNPEnsembl.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.

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...)1 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.

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

Protein-protein interaction databases

BioGridi112408. 39 interactors.
IntActiP14672. 2 interactors.
MINTiMINT-232088.
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.
OMAiSHTHRQP.
OrthoDBiEOG091G0A9K.
PhylomeDBiP14672.
TreeFamiTF313762.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR002441. Glc_transpt_4.
IPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR003663. Sugar/inositol_transpt.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
PRINTSiPR01193. GLUCTRSPORT4.
PR00171. SUGRTRNSPORT.
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00879. SP. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
PS00217. SUGAR_TRANSPORT_2. 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: 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 rs35198331dbSNPEnsembl.1
Natural variantiVAR_01206078T → S.Corresponds to variant rs5434dbSNPEnsembl.1
Natural variantiVAR_020336358A → V.Corresponds to variant rs8192702dbSNPEnsembl.1
Natural variantiVAR_007170383V → I in NIDDM. 3 PublicationsCorresponds to variant rs121434581dbSNPEnsembl.1
Natural variantiVAR_007171385I → T.1 PublicationCorresponds to variant rs775242206dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

Wikipedia

GLUT4 entry

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.

3D structure databases

ProteinModelPortaliP14672.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112408. 39 interactors.
IntActiP14672. 2 interactors.
MINTiMINT-232088.
STRINGi9606.ENSP00000320935.

Chemistry databases

ChEMBLiCHEMBL5874.

Protein family/group databases

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

PTM databases

iPTMnetiP14672.
PhosphoSitePlusiP14672.
SwissPalmiP14672.

Polymorphism and mutation databases

BioMutaiSLC2A4.
DMDMi121761.

Proteomic databases

EPDiP14672.
PaxDbiP14672.
PeptideAtlasiP14672.
PRIDEiP14672.

Protocols and materials databases

DNASUi6517.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6517.
DisGeNETi6517.
GeneCardsiSLC2A4.
HGNCiHGNC:11009. SLC2A4.
HPAiCAB016544.
MalaCardsiSLC2A4.
MIMi125853. phenotype.
138190. gene.
neXtProtiNX_P14672.
OpenTargetsiENSG00000181856.
PharmGKBiPA35879.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000181856-MONOMER.
ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-428790. Facilitative Na+-independent glucose transporters.
R-HSA-70153. Glucose transport.
SIGNORiP14672.

Miscellaneous databases

GeneWikiiGLUT4.
GenomeRNAii6517.
PROiP14672.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181856.
CleanExiHS_SLC2A4.
ExpressionAtlasiP14672. baseline and differential.
GenevisibleiP14672. HS.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR002441. Glc_transpt_4.
IPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR003663. Sugar/inositol_transpt.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
PRINTSiPR01193. GLUCTRSPORT4.
PR00171. SUGRTRNSPORT.
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00879. SP. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
PS00217. SUGAR_TRANSPORT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGTR4_HUMAN
AccessioniPrimary (citable) accession number: P14672
Secondary accession number(s): Q05BQ3, Q14CX2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 30, 2016
This is version 197 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

Miscellaneous

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

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

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.