P14672 (GTR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

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. Ref.5
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.10 Ref.11 Ref.12
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 process	Sugar transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Traceable author statement. Source: Reactome cellular response to insulin stimulus Inferred from direct assay. Source: UniProtKB glucose homeostasis Inferred from direct assay. Source: BHF-UCL glucose import Non-traceable author statement. Source: BHF-UCL
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: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAXX	Q9UER7	7	EBI-367146,EBI-77321

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	24	Cytoplasmic Potential
	Transmembrane	25 – 45	21	Helical; Name=1; Potential
	Topological domain	46 – 81	36	Extracellular Potential
	Transmembrane	82 – 102	21	Helical; Name=2; Potential
	Topological domain	103 – 111	9	Cytoplasmic Potential
	Transmembrane	112 – 132	21	Helical; Name=3; Potential
	Topological domain	133 – 142	10	Extracellular Potential
	Transmembrane	143 – 163	21	Helical; Name=4; Potential
	Topological domain	164 – 171	8	Cytoplasmic Potential
	Transmembrane	172 – 192	21	Helical; Name=5; Potential
	Topological domain	193 – 201	9	Extracellular Potential
	Transmembrane	202 – 222	21	Helical; Name=6; Potential
	Topological domain	223 – 287	65	Cytoplasmic Potential
	Transmembrane	288 – 308	21	Helical; Name=7; Potential
	Topological domain	309 – 323	15	Extracellular Potential
	Transmembrane	324 – 344	21	Helical; Name=8; Potential
	Topological domain	345 – 353	9	Cytoplasmic Potential
	Transmembrane	354 – 374	21	Helical; Name=9; Potential
	Topological domain	375 – 384	10	Extracellular Potential
	Transmembrane	385 – 405	21	Helical; Name=10; Potential
	Topological domain	406 – 417	12	Cytoplasmic Potential
	Transmembrane	418 – 438	21	Helical; Name=11; Potential
	Topological domain	439 – 445	7	Extracellular Potential
	Transmembrane	446 – 466	21	Helical; Name=12; Potential
	Topological domain	467 – 509	43	Cytoplasmic Potential
	Region	7 – 13	7	SRFBP1-binding
	Region	295 – 297	3	Defines substrate specificity By similarity
	Motif	489 – 490	2	Dileucine internalization motif
Amino acid modifications
	Modified residue	274	1	Phosphoserine; by SGK1 Ref.8
	Modified residue	488	1	Phosphoserine By similarity
	Glycosylation	57	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Natural variant	55	1	S → R. Corresponds to variant rs35198331 [ dbSNP | Ensembl ].		VAR_052503
	Natural variant	78	1	T → S. Corresponds to variant rs5434 [ dbSNP | Ensembl ].		VAR_012060
	Natural variant	358	1	A → V. Corresponds to variant rs8192702 [ dbSNP | Ensembl ].		VAR_020336
	Natural variant	383	1	V → I in NIDDM. Ref.10 Ref.11 Ref.12		VAR_007170
	Natural variant	385	1	I → T. Ref.2		VAR_007171
Experimental info
	Mutagenesis	489 – 490	2	LL → AA: Changes subcellular location mainly to the plasma membrane. Ref.5
	Sequence conflict	151 – 154	4	Missing in AAA52569. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P14672 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 8E20CD97562C1EBF	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

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]	"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: 17382906] [Abstract] Cited for: PHOSPHORYLATION AT SER-274 BY SGK1.
[9]	"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: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"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.
[11]	"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.
[12]	"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.

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.
IPI	IPI00027281.
PIR	A33801. A49158.
RefSeq	NP_001033.1. NM_001042.2.
UniGene	Hs.380691.
3D structure databases
ProteinModelPortal	P14672.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14672. 1 interaction.
MINT	MINT-232088.
STRING	P14672.
PTM databases
PhosphoSite	P14672.
Polymorphism databases
DMDM	121761.
Proteomic databases
PRIDE	P14672.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317370; ENSP00000320935; ENSG00000181856.
GeneID	6517.
KEGG	hsa:6517.
UCSC	uc002gfo.1. human.
Organism-specific databases
CTD	6517.
GeneCards	GC17P007186.
H-InvDB	HIX0039179.
HGNC	HGNC:11009. SLC2A4.
HPA	CAB016544.
MIM	125853. phenotype. 138190. gene.
neXtProt	NX_P14672.
PharmGKB	PA35879.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06425.
GeneTree	ENSGT00600000084007.
HOGENOM	HBG744444.
HOVERGEN	HBG014816.
InParanoid	P14672.
OMA	ISAAFHR.
OrthoDB	EOG4BG8W5.
PhylomeDB	P14672.
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_111045. Developmental Biology. REACT_15518. Transmembrane transport of small molecules. REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	P14672.
Bgee	P14672.
CleanEx	HS_SLC2A4.
Genevestigator	P14672.
GermOnline	ENSG00000181856. Homo sapiens.
Family and domain databases
InterPro	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]
KO	K07191.
Pfam	PF00083. Sugar_tr. 1 hit. [Graphical view]
PRINTS	PR01193. GLUCTRSPORT4. PR00171. SUGRTRNSPORT.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
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
NextBio	25341.
SOURCE	Search...

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:	January 25, 2012
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.