Solute carrier family 2, facilitated glucose transporter member 4

Contribute

Send feedback

Read comments (1) or add your own

Reviewed, UniProtKB/Swiss-Prot P14672 (GTR4_HUMAN)

Last modified June 16, 2009. Version 115. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data |

Customize display

text xml rdf/xml gff fasta

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein names

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 names

Name:	SLC2A4
Synonyms:	GLUT4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Insulin-regulated facilitative glucose transporter.
Subunit structure	Binds to DAXX. Interacts via its N-terminus with SRFBP1. Ref.6 Ref.7
Subcellular location	Endomembrane system; Multi-pass membrane protein. Cytoplasm › perinuclear 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.
Tissue specificity	Skeletal and cardiac muscles; brown and white fat.
Post-translational modification	Sumoylated. Ref.6
Involvement in disease	Defects in SLC2A4 may be a cause of noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. Defects in SLC2A4 may be a cause of certain post-receptor defects in NIDDM. The variant in position Ile-383 is found in a small number of NIDDM patients, but seems not to be found in nondiabetic subjects. Ref.8 Ref.9 Ref.10
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]

Hide | Top

Ontologies

Keywords
Biological process	Sugar transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Transmembrane
PTM	Glycoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Traceable author statement. Source: ProtInc glucose homeostasis Inferred from direct assay. Source: UniProtKB glucose import Non-traceable author statement. Source: UniProtKB transmembrane transport Inferred from electronic annotation. Source: InterPro
Cellular component	external side of plasma membrane Inferred from direct assay. Source: MGI integral to plasma membrane Traceable author statement. Source: ProtInc perinuclear region of cytoplasm Inferred from direct assay. Source: MGI vesicle membrane Inferred from direct assay. Source: MGI
Molecular function	glucose transmembrane transporter activity Traceable author statement. Source: ProtInc protein binding Ref.6 Inferred from physical interaction. Source: IntAct sugar:hydrogen symporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Hide | Top

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	3	EBI-367146,EBI-77321

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 509

509

Solute carrier family 2, facilitated glucose transporter member 4

PRO_0000050363

Regions

Topological domain

1 – 24

Cytoplasmic Potential

Transmembrane

25 – 45

1 Potential

Topological domain

46 – 81

Extracellular Potential

Transmembrane

82 – 102

2 Potential

Topological domain

103 – 111

Cytoplasmic Potential

Transmembrane

112 – 132

3 Potential

Topological domain

133 – 142

Extracellular Potential

Transmembrane

143 – 163

4 Potential

Topological domain

164 – 171

Cytoplasmic Potential

Transmembrane

172 – 192

5 Potential

Topological domain

193 – 201

Extracellular Potential

Transmembrane

202 – 222

6 Potential

Topological domain

223 – 287

Cytoplasmic Potential

Transmembrane

288 – 308

7 Potential

Topological domain

309 – 323

Extracellular Potential

Transmembrane

324 – 344

8 Potential

Topological domain

345 – 353

Cytoplasmic Potential

Transmembrane

354 – 374

9 Potential

Topological domain

375 – 384

Extracellular Potential

Transmembrane

385 – 405

10 Potential

Topological domain

406 – 417

Cytoplasmic Potential

Transmembrane

418 – 438

11 Potential

Topological domain

439 – 445

Extracellular Potential

Transmembrane

446 – 466

12 Potential

Topological domain

467 – 509

Cytoplasmic Potential

Region

7 – 13

SRFBP1-binding

Region

295 – 297

Defines substrate specificity By similarity

Motif

489 – 490

Dileucine internalization motif

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

S → R: dbSNP rs35198331.

VAR_052503

Natural variant

T → S: dbSNP rs5434.

VAR_012060

Natural variant

358

A → V: dbSNP rs8192702.

VAR_020336

Natural variant

383

V → I in NIDDM. Ref.8 Ref.9 Ref.10

VAR_007170

Natural variant

385

I → T Ref.2

VAR_007171

Experimental info

Mutagenesis

489 – 490

LL → AA: Changes subcellular location mainly to the plasma membrane. Ref.5

Sequence conflict

151 – 154

Missing in AAA52569. Ref.2

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

P14672-1 [UniParc].

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

FASTA

509

54,787

        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

Hide | Top

References

	« Hide 'large scale' referencesShow '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: 2656669] [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: 1397719] [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: 15489334] [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: 7916714] [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: 8300557] [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: 11842083] [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: 16647043] [Abstract] Cited for: INTERACTION WITH SRFBP1.
[8]	"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: 1918382] [Abstract] Cited for: VARIANT NIDDM ILE-383.
[9]	"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: 1756912] [Abstract] Cited for: VARIANT NIDDM ILE-383.
[10]	"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: 1521731] [Abstract] Cited for: VARIANT NIDDM ILE-383.
+	Additional computationally mapped references.

Hide | Top

Web resources

Wikipedia

GLUT4 entry

Hide | Top

Cross-references

Sequence databases
	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.
IPI	IPI00027281.
PIR	A33801. A49158.
RefSeq	NP_001033.1.
UniGene	Hs.380691
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P14672. 1 interaction.
PTM databases
PhosphoSite	P14672.
Proteomic databases
PRIDE	P14672.
Genome annotation databases
Ensembl	ENSG00000181856. Homo sapiens. [Contig view]
GeneID	6517.
KEGG	hsa:6517.
Organism-specific databases
GeneCards	GC17P007125.
H-InvDB	HIX0039179.
HGNC	HGNC:11009. SLC2A4.
HPA	CAB016544.
MIM	125853. phenotype. 138190. gene.
PharmGKB	PA35879.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P14672.
HOVERGEN	P14672.
OMA	P14672. RAMLVNN.
Enzyme and pathway databases
Pathway_Interaction_DB	arf6_traffickingpathway. Arf6 trafficking events. pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. insulin_glucose_pathway. Insulin-mediated glucose transport.
Reactome	REACT_11193. Metabolism of vitamins and cofactors. REACT_474. Metabolism of carbohydrates.
Gene expression databases
Bgee	P14672.
CleanEx	HS_SLC2A4.
GermOnline	ENSG00000181856. Homo sapiens.
Family and domain databases
InterPro	IPR002441. Glc_transpt_4. IPR005828. Sub_transporter. IPR003663. Sugar/inositol_transpt. IPR005829. Sugar_transporter_CS. [Graphical view]
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
PRINTS	PR01193. GLUCTRSPORT4. PR00171. SUGRTRNSPORT.
TIGRFAMs	TIGR00879. SP. 1 hit.
PROSITE	PS50850. MFS. 1 hit. PS00216. SUGAR_TRANSPORT_1. 1 hit. PS00217. SUGAR_TRANSPORT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	25341.
SOURCE	Search...

Hide | Top

Entry information

Entry name

GTR4_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top

Relevant documents

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents