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P14672

- GTR4_HUMAN

UniProt

P14672 - GTR4_HUMAN

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Protein

Solute carrier family 2, facilitated glucose transporter member 4

Gene
SLC2A4, GLUT4
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Insulin-regulated facilitative glucose transporter.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei333 – 3331Monosaccharide By similarity
Binding sitei404 – 4041Monosaccharide By similarity

GO - Molecular functioni

  1. D-glucose transmembrane transporter activity Source: Ensembl
  2. glucose transmembrane transporter activity Source: ProtInc
  3. protein binding Source: UniProtKB

GO - Biological processi

  1. amylopectin biosynthetic process Source: Ensembl
  2. brown fat cell differentiation Source: Ensembl
  3. carbohydrate metabolic process Source: Reactome
  4. cellular response to insulin stimulus Source: UniProtKB
  5. cellular response to osmotic stress Source: Ensembl
  6. glucose homeostasis Source: BHF-UCL
  7. glucose import Source: BHF-UCL
  8. glucose transport Source: UniProtKB
  9. hexose transport Source: Reactome
  10. membrane organization Source: Reactome
  11. response to ethanol Source: Ensembl
  12. small molecule metabolic process Source: Reactome
  13. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Sugar transport, Transport

Enzyme and pathway databases

ReactomeiREACT_147867. Translocation of GLUT4 to the plasma membrane.
REACT_19343. Facilitative Na+-independent glucose transporters.
REACT_212. Glucose transport.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.

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
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:11009. SLC2A4.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2424Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei25 – 4521Helical; Name=1; Reviewed predictionAdd
BLAST
Topological domaini46 – 8136Extracellular Reviewed predictionAdd
BLAST
Transmembranei82 – 10221Helical; Name=2; Reviewed predictionAdd
BLAST
Topological domaini103 – 1119Cytoplasmic Reviewed prediction
Transmembranei112 – 13221Helical; Name=3; Reviewed predictionAdd
BLAST
Topological domaini133 – 14210Extracellular Reviewed prediction
Transmembranei143 – 16321Helical; Name=4; Reviewed predictionAdd
BLAST
Topological domaini164 – 1718Cytoplasmic Reviewed prediction
Transmembranei172 – 19221Helical; Name=5; Reviewed predictionAdd
BLAST
Topological domaini193 – 2019Extracellular Reviewed prediction
Transmembranei202 – 22221Helical; Name=6; Reviewed predictionAdd
BLAST
Topological domaini223 – 28765Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei288 – 30821Helical; Name=7; Reviewed predictionAdd
BLAST
Topological domaini309 – 32315Extracellular Reviewed predictionAdd
BLAST
Transmembranei324 – 34421Helical; Name=8; Reviewed predictionAdd
BLAST
Topological domaini345 – 3539Cytoplasmic Reviewed prediction
Transmembranei354 – 37421Helical; Name=9; Reviewed predictionAdd
BLAST
Topological domaini375 – 38410Extracellular Reviewed prediction
Transmembranei385 – 40521Helical; Name=10; Reviewed predictionAdd
BLAST
Topological domaini406 – 41712Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei418 – 43821Helical; Name=11; Reviewed predictionAdd
BLAST
Topological domaini439 – 4457Extracellular Reviewed prediction
Transmembranei446 – 46621Helical; Name=12; Reviewed predictionAdd
BLAST
Topological domaini467 – 50943Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. clathrin-coated vesicle Source: UniProtKB
  2. coated pit Source: Ensembl
  3. endomembrane system Source: UniProtKB
  4. external side of plasma membrane Source: MGI
  5. extracellular vesicular exosome Source: Ensembl
  6. insulin-responsive compartment Source: UniProtKB
  7. integral component of plasma membrane Source: ProtInc
  8. membrane Source: ProtInc
  9. multivesicular body Source: Ensembl
  10. perinuclear region of cytoplasm Source: UniProtKB
  11. plasma membrane Source: UniProtKB
  12. sarcolemma Source: Ensembl
  13. trans-Golgi network transport vesicle Source: Ensembl
  14. 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) [MIM:125853]: A 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.
Note: The disease may be caused by mutations affecting the gene represented in this entry.3 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti383 – 3831V → I in NIDDM. 3 Publications
Corresponds to variant rs121434581 [ dbSNP | Ensembl ].
VAR_007170

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi489 – 4902LL → AA: Changes subcellular location mainly to the plasma membrane. 1 Publication

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

MIMi125853. phenotype.
PharmGKBiPA35879.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 509509Solute carrier family 2, facilitated glucose transporter member 4PRO_0000050363Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi57 – 571N-linked (GlcNAc...)1 Publication
Modified residuei274 – 2741Phosphoserine; by SGK11 Publication

Post-translational modificationi

Sumoylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP14672.
PRIDEiP14672.

PTM databases

PhosphoSiteiP14672.

Expressioni

Tissue specificityi

Skeletal and cardiac muscles; brown and white fat.

Gene expression databases

ArrayExpressiP14672.
BgeeiP14672.
CleanExiHS_SLC2A4.
GenevestigatoriP14672.

Organism-specific databases

HPAiCAB016544.

Interactioni

Subunit structurei

Interacts with NDUFA9 By similarity. Binds to DAXX. Interacts via its N-terminus with SRFBP1.2 Publications

Protein-protein interaction databases

BioGridi112408. 37 interactions.
IntActiP14672. 1 interaction.
MINTiMINT-232088.
STRINGi9606.ENSP00000320935.

Structurei

3D structure databases

ProteinModelPortaliP14672.
SMRiP14672. Positions 31-481.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni7 – 137SRFBP1-binding
Regioni298 – 3047Monosaccharide binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi489 – 4902Dileucine internalization motif

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0477.
HOGENOMiHOG000202871.
HOVERGENiHBG014816.
InParanoidiP14672.
KOiK07191.
OMAiAMLVNNI.
PhylomeDBiP14672.
TreeFamiTF313762.

Family and domain databases

InterProiIPR002441. Glc_transpt_4.
IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR005828. Sub_transporter.
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]

Sequencei

Sequence statusi: Complete.

P14672-1 [UniParc]FASTAAdd to Basket

« Hide

MPSGFQQIGS EDGEPPQQRV TGTLVLAVFS AVLGSLQFGY NIGVINAPQK    50
VIEQSYNETW LGRQGPEGPS SIPPGTLTTL WALSVAIFSV GGMISSFLIG 100
IISQWLGRKR AMLVNNVLAV LGGSLMGLAN AAASYEMLIL GRFLIGAYSG 150
LTSGLVPMYV GEIAPTHLRG ALGTLNQLAI VIGILIAQVL GLESLLGTAS 200
LWPLLLGLTV LPALLQLVLL PFCPESPRYL YIIQNLEGPA RKSLKRLTGW 250
ADVSGVLAEL KDEKRKLERE RPLSLLQLLG SRTHRQPLII AVVLQLSQQL 300
SGINAVFYYS TSIFETAGVG QPAYATIGAG VVNTVFTLVS VLLVERAGRR 350
TLHLLGLAGM CGCAILMTVA LLLLERVPAM SYVSIVAIFG FVAFFEIGPG 400
PIPWFIVAEL FSQGPRPAAM AVAGFSNWTS NFIIGMGFQY VAEAMGPYVF 450
LLFAVLLLGF FIFTFLRVPE TRGRTFDQIS AAFHRTPSLL EQEVKPSTEL 500
EYLGPDEND 509
Length:509
Mass (Da):54,787
Last modified:April 1, 1990 - v1
Checksum:i8E20CD97562C1EBF
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551S → R.
Corresponds to variant rs35198331 [ dbSNP | Ensembl ].
VAR_052503
Natural varianti78 – 781T → S.
Corresponds to variant rs5434 [ dbSNP | Ensembl ].
VAR_012060
Natural varianti358 – 3581A → V.
Corresponds to variant rs8192702 [ dbSNP | Ensembl ].
VAR_020336
Natural varianti383 – 3831V → I in NIDDM. 3 Publications
Corresponds to variant rs121434581 [ dbSNP | Ensembl ].
VAR_007170
Natural varianti385 – 3851I → T.1 Publication
VAR_007171

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti151 – 1544Missing in AAA52569. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M20747 mRNA. Translation: AAA59189.1.
M91463 Genomic DNA. Translation: AAA52569.1.
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.
PIRiA49158. A33801.
RefSeqiNP_001033.1. NM_001042.2.
UniGeneiHs.380691.

Genome annotation databases

EnsembliENST00000317370; ENSP00000320935; ENSG00000181856.
GeneIDi6517.
KEGGihsa:6517.
UCSCiuc002gfp.3. human.

Polymorphism databases

DMDMi121761.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

GLUT4 entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M20747 mRNA. Translation: AAA59189.1 .
M91463 Genomic DNA. Translation: AAA52569.1 .
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 .
CCDSi CCDS11097.1.
PIRi A49158. A33801.
RefSeqi NP_001033.1. NM_001042.2.
UniGenei Hs.380691.

3D structure databases

ProteinModelPortali P14672.
SMRi P14672. Positions 31-481.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112408. 37 interactions.
IntActi P14672. 1 interaction.
MINTi MINT-232088.
STRINGi 9606.ENSP00000320935.

Chemistry

ChEMBLi CHEMBL5874.
GuidetoPHARMACOLOGYi 878.

Protein family/group databases

TCDBi 2.A.1.1.80. the major facilitator superfamily (mfs).

PTM databases

PhosphoSitei P14672.

Polymorphism databases

DMDMi 121761.

Proteomic databases

PaxDbi P14672.
PRIDEi P14672.

Protocols and materials databases

DNASUi 6517.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000317370 ; ENSP00000320935 ; ENSG00000181856 .
GeneIDi 6517.
KEGGi hsa:6517.
UCSCi uc002gfp.3. human.

Organism-specific databases

CTDi 6517.
GeneCardsi GC17P007186.
HGNCi HGNC:11009. SLC2A4.
HPAi CAB016544.
MIMi 125853. phenotype.
138190. gene.
neXtProti NX_P14672.
PharmGKBi PA35879.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0477.
HOGENOMi HOG000202871.
HOVERGENi HBG014816.
InParanoidi P14672.
KOi K07191.
OMAi AMLVNNI.
PhylomeDBi P14672.
TreeFami TF313762.

Enzyme and pathway databases

Reactomei REACT_147867. Translocation of GLUT4 to the plasma membrane.
REACT_19343. Facilitative Na+-independent glucose transporters.
REACT_212. Glucose transport.
REACT_27161. Transcriptional regulation of white adipocyte differentiation.

Miscellaneous databases

GeneWikii GLUT4.
GenomeRNAii 6517.
NextBioi 25341.
PROi P14672.
SOURCEi Search...

Gene expression databases

ArrayExpressi P14672.
Bgeei P14672.
CleanExi HS_SLC2A4.
Genevestigatori P14672.

Family and domain databases

InterProi IPR002441. Glc_transpt_4.
IPR020846. MFS_dom.
IPR016196. MFS_dom_general_subst_transpt.
IPR005828. Sub_transporter.
IPR003663. Sugar/inositol_transpt.
IPR005829. Sugar_transporter_CS.
[Graphical view ]
Pfami PF00083. Sugar_tr. 1 hit.
[Graphical view ]
PRINTSi PR01193. GLUCTRSPORT4.
PR00171. SUGRTRNSPORT.
SUPFAMi SSF103473. SSF103473. 1 hit.
TIGRFAMsi TIGR00879. SP. 1 hit.
PROSITEi PS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
PS00217. SUGAR_TRANSPORT_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues."
    Fukumoto H., Kayano T., Buse J.B., Edwards Y., Pilch P.F., Bell G.I., Seino S.
    J. Biol. Chem. 264:7776-7779(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Human GLUT4/muscle-fat glucose-transporter gene. Characterization and genetic variation."
    Buse J.B., Yasuda K., Lay T.P., Seo T.S., Olson A.L., Pessin J.E., Karam J.H., Seino S., Bell G.I.
    Diabetes 41:1436-1445(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-385.
  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].
    Tissue: Colon.
  4. "Identification of the 5' end of the gene encoding a human insulin-responsive glucose transporter."
    Chiaramonte R., Martini R., Taramelli R., Comi P.
    Gene 130:307-308(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
  5. "A Leu-Leu sequence is essential for COOH-terminal targeting signal of GLUT4 glucose transporter in fibroblasts."
    Verhey K.J., Birnbaum M.J.
    J. Biol. Chem. 269:2353-2356(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 489-LEU-LEU-490.
  6. "The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1."
    Lalioti V.S., Vergarajauregui S., Pulido D., Sandoval I.V.
    J. Biol. Chem. 277:19783-19791(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DAXX, SUMOYLATION.
  7. "Identification and characterization of p49/STRAP as a novel GLUT4-binding protein."
    Lisinski I., Matsumoto H., Yver D.R., Schuermann A., Cushman S.W., Al-Hasani H.
    Biochem. Biophys. Res. Commun. 344:1179-1185(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SRFBP1.
  8. "Role of SGK1 kinase in regulating glucose transport via glucose transporter GLUT4."
    Jeyaraj S., Boehmer C., Lang F., Palmada M.
    Biochem. Biophys. Res. Commun. 356:629-635(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-274 BY SGK1.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
    Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
    Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57.
    Tissue: Leukemic T-cell.
  11. "Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus."
    Kusari J., Verma U.S., Buse J.B., Henry R.R., Olefsky J.M.
    J. Clin. Invest. 88:1323-1330(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT NIDDM ILE-383.
  12. "Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects."
    Choi W.H., O'Rahilly S., Buse J.B., Rees A., Morgan R., Flier J.S., Moller D.E.
    Diabetes 40:1712-1718(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT NIDDM ILE-383.
  13. "Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population."
    O'Rahilly S., Krook A., Morgan R., Rees A., Flier J.S., Moller D.E.
    Diabetologia 35:486-489(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT NIDDM ILE-383.

Entry informationi

Entry nameiGTR4_HUMAN
AccessioniPrimary (citable) accession number: P14672
Secondary accession number(s): Q14CX2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: September 3, 2014
This is version 172 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

External Data

Dasty 3

Similar proteinsi