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P14672 (GTR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 2, facilitated glucose transporter member 4
Alternative name(s):
Glucose transporter type 4, insulin-responsive
Short name=GLUT-4
Gene names
Name:SLC2A4
Synonyms:GLUT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length509 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Insulin-regulated facilitative glucose transporter.

Subunit structure

Interacts with NDUFA9 By similarity. Binds to DAXX. Interacts via its N-terminus with SRFBP1. Ref.6 Ref.7

Subcellular location

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. Ref.5

Tissue specificity

Skeletal and cardiac muscles; brown and white fat.

Post-translational modification

Sumoylated. Ref.6

Involvement in disease

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. Ref.11 Ref.12 Ref.13

Miscellaneous

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

Sequence similarities

Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily. [View classification]

Ontologies

Keywords
   Biological processSugar transport
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processamylopectin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular response to insulin stimulus

Inferred from direct assay PubMed 12556481. Source: UniProtKB

cellular response to osmotic stress

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from direct assay PubMed 17003346. Source: BHF-UCL

glucose import

Non-traceable author statement PubMed 11742412. Source: BHF-UCL

glucose transport

Traceable author statement PubMed 12556481. Source: UniProtKB

hexose transport

Traceable author statement. Source: Reactome

membrane organization

Traceable author statement. Source: Reactome

response to ethanol

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentclathrin-coated vesicle

Inferred from direct assay PubMed 19478182. Source: UniProtKB

coated pit

Inferred from electronic annotation. Source: Ensembl

endomembrane system

Inferred from sequence or structural similarity. Source: UniProtKB

external side of plasma membrane

Inferred from direct assay PubMed 14562105. Source: MGI

extracellular vesicular exosome

Inferred from electronic annotation. Source: Ensembl

insulin-responsive compartment

Inferred from direct assay PubMed 19590752. Source: UniProtKB

integral component of plasma membrane

Traceable author statement PubMed 2649253. Source: ProtInc

membrane

Traceable author statement PubMed 2649253. Source: ProtInc

multivesicular body

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from direct assay PubMed 12556481PubMed 19590752. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 12556481. Source: UniProtKB

sarcolemma

Inferred from electronic annotation. Source: Ensembl

trans-Golgi network transport vesicle

Inferred from electronic annotation. Source: Ensembl

vesicle membrane

Inferred from direct assay PubMed 14562105. Source: MGI

   Molecular_functionD-glucose transmembrane transporter activity

Inferred from electronic annotation. Source: Ensembl

glucose transmembrane transporter activity

Traceable author statement PubMed 2649253. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 19478182. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 509509Solute carrier family 2, facilitated glucose transporter member 4
PRO_0000050363

Regions

Topological domain1 – 2424Cytoplasmic Potential
Transmembrane25 – 4521Helical; Name=1; Potential
Topological domain46 – 8136Extracellular Potential
Transmembrane82 – 10221Helical; Name=2; Potential
Topological domain103 – 1119Cytoplasmic Potential
Transmembrane112 – 13221Helical; Name=3; Potential
Topological domain133 – 14210Extracellular Potential
Transmembrane143 – 16321Helical; Name=4; Potential
Topological domain164 – 1718Cytoplasmic Potential
Transmembrane172 – 19221Helical; Name=5; Potential
Topological domain193 – 2019Extracellular Potential
Transmembrane202 – 22221Helical; Name=6; Potential
Topological domain223 – 28765Cytoplasmic Potential
Transmembrane288 – 30821Helical; Name=7; Potential
Topological domain309 – 32315Extracellular Potential
Transmembrane324 – 34421Helical; Name=8; Potential
Topological domain345 – 3539Cytoplasmic Potential
Transmembrane354 – 37421Helical; Name=9; Potential
Topological domain375 – 38410Extracellular Potential
Transmembrane385 – 40521Helical; Name=10; Potential
Topological domain406 – 41712Cytoplasmic Potential
Transmembrane418 – 43821Helical; Name=11; Potential
Topological domain439 – 4457Extracellular Potential
Transmembrane446 – 46621Helical; Name=12; Potential
Topological domain467 – 50943Cytoplasmic Potential
Region7 – 137SRFBP1-binding
Region295 – 2973Defines substrate specificity By similarity
Motif489 – 4902Dileucine internalization motif

Amino acid modifications

Modified residue2741Phosphoserine; by SGK1 Ref.8
Glycosylation571N-linked (GlcNAc...) Ref.10

Natural variations

Natural variant551S → R.
Corresponds to variant rs35198331 [ dbSNP | Ensembl ].
VAR_052503
Natural variant781T → S.
Corresponds to variant rs5434 [ dbSNP | Ensembl ].
VAR_012060
Natural variant3581A → V.
Corresponds to variant rs8192702 [ dbSNP | Ensembl ].
VAR_020336
Natural variant3831V → I in NIDDM. Ref.11 Ref.12 Ref.13
Corresponds to variant rs121434581 [ dbSNP | Ensembl ].
VAR_007170
Natural variant3851I → T. Ref.2
VAR_007171

Experimental info

Mutagenesis489 – 4902LL → AA: Changes subcellular location mainly to the plasma membrane. Ref.5
Sequence conflict151 – 1544Missing in AAA52569. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P14672 [UniParc].

Last modified April 1, 1990. Version 1.
Checksum: 8E20CD97562C1EBF

FASTA50954,787
        10         20         30         40         50         60 
MPSGFQQIGS EDGEPPQQRV TGTLVLAVFS AVLGSLQFGY NIGVINAPQK VIEQSYNETW 

        70         80         90        100        110        120 
LGRQGPEGPS SIPPGTLTTL WALSVAIFSV GGMISSFLIG IISQWLGRKR AMLVNNVLAV 

       130        140        150        160        170        180 
LGGSLMGLAN AAASYEMLIL GRFLIGAYSG LTSGLVPMYV GEIAPTHLRG ALGTLNQLAI 

       190        200        210        220        230        240 
VIGILIAQVL GLESLLGTAS LWPLLLGLTV LPALLQLVLL PFCPESPRYL YIIQNLEGPA 

       250        260        270        280        290        300 
RKSLKRLTGW ADVSGVLAEL KDEKRKLERE RPLSLLQLLG SRTHRQPLII AVVLQLSQQL 

       310        320        330        340        350        360 
SGINAVFYYS TSIFETAGVG QPAYATIGAG VVNTVFTLVS VLLVERAGRR TLHLLGLAGM 

       370        380        390        400        410        420 
CGCAILMTVA LLLLERVPAM SYVSIVAIFG FVAFFEIGPG PIPWFIVAEL FSQGPRPAAM 

       430        440        450        460        470        480 
AVAGFSNWTS NFIIGMGFQY VAEAMGPYVF LLFAVLLLGF FIFTFLRVPE TRGRTFDQIS 

       490        500 
AAFHRTPSLL EQEVKPSTEL EYLGPDEND 

« Hide

References

« Hide 'large scale' references
[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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Wikipedia

GLUT4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11097.1.
PIRA33801. A49158.
RefSeqNP_001033.1. NM_001042.2.
UniGeneHs.380691.

3D structure databases

ProteinModelPortalP14672.
SMRP14672. Positions 31-481.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112408. 37 interactions.
IntActP14672. 1 interaction.
MINTMINT-232088.
STRING9606.ENSP00000320935.

Chemistry

ChEMBLCHEMBL5874.
GuidetoPHARMACOLOGY878.

Protein family/group databases

TCDB2.A.1.1.80. the major facilitator superfamily (mfs).

PTM databases

PhosphoSiteP14672.

Polymorphism databases

DMDM121761.

Proteomic databases

PaxDbP14672.
PRIDEP14672.

Protocols and materials databases

DNASU6517.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317370; ENSP00000320935; ENSG00000181856.
GeneID6517.
KEGGhsa:6517.
UCSCuc002gfp.3. human.

Organism-specific databases

CTD6517.
GeneCardsGC17P007186.
HGNCHGNC:11009. SLC2A4.
HPACAB016544.
MIM125853. phenotype.
138190. gene.
neXtProtNX_P14672.
PharmGKBPA35879.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0477.
HOGENOMHOG000202871.
HOVERGENHBG014816.
InParanoidP14672.
KOK07191.
OMAAMLVNNI.
PhylomeDBP14672.
TreeFamTF313762.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP14672.
BgeeP14672.
CleanExHS_SLC2A4.
GenevestigatorP14672.

Family and domain databases

InterProIPR002441. 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]
PfamPF00083. Sugar_tr. 1 hit.
[Graphical view]
PRINTSPR01193. GLUCTRSPORT4.
PR00171. SUGRTRNSPORT.
SUPFAMSSF103473. SSF103473. 1 hit.
TIGRFAMsTIGR00879. SP. 1 hit.
PROSITEPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
PS00217. SUGAR_TRANSPORT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGLUT4.
GenomeRNAi6517.
NextBio25341.
PROP14672.
SOURCESearch...

Entry information

Entry nameGTR4_HUMAN
AccessionPrimary (citable) accession number: P14672
Secondary accession number(s): Q14CX2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: July 9, 2014
This is version 171 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM