P19357 (GTR4_RAT) 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:	Glut-4, Glut4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity. Interacts with NDUFA9. Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Endomembrane system; Multi-pass membrane protein By similarity. Cytoplasm › perinuclear region By similarity. 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 By similarity. Ref.8
Tissue specificity	Skeletal and cardiac muscles; brown and white fat.
Post-translational modification	Sumoylated By similarity.
Involvement in disease	It is a candidate for certain post-receptor defects in non-insulin-dependent diabetes mellitus.
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	Cell membrane Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amylopectin biosynthetic process Inferred from electronic annotation. Source: Compara brown fat cell differentiation Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from sequence or structural similarity. Source: UniProtKB cellular response to osmotic stress Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from electronic annotation. Source: Compara response to ethanol Inferred from expression pattern PubMed 18959809. Source: RGD
Cellular_component	coated pit Inferred from direct assay PubMed 1881917. Source: RGD external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular vesicular exosome Inferred from electronic annotation. Source: Compara insulin-responsive compartment Inferred from direct assay PubMed 8366094PubMed 9271094PubMed 9516411PubMed 9880520. Source: RGD integral to plasma membrane Inferred from electronic annotation. Source: Compara multivesicular body Inferred from direct assay PubMed 1881917. Source: RGD perinuclear region of cytoplasm Inferred from direct assay PubMed 12388133PubMed 9271094. Source: RGD sarcolemma Inferred from direct assay PubMed 12388133PubMed 1881917. Source: RGD trans-Golgi network transport vesicle Inferred from electronic annotation. Source: Compara vesicle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	D-glucose transmembrane transporter activity Inferred from direct assay PubMed 1733237PubMed 2211693. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Actn4	Q9QXQ0	3	EBI-915426,EBI-919056
Gapdh	P04797	2	EBI-915426,EBI-349219

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_0000050366
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 By similarity
	Region	295 – 297	3	Defines substrate specificity By similarity
	Motif	489 – 490	2	Dileucine internalization motif Potential
Amino acid modifications
	Modified residue	274	1	Phosphoserine; by SGK1 By similarity
	Modified residue	488	1	Phosphoserine By similarity
	Glycosylation	57	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	349	1	R → Q in AAA41451. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P19357 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: DA50321E99E4CA90	FASTA	509	54,896
	10 20 30 40 50 60 MPSGFQQIGS EDGEPPQQRV TGTLVLAVFS AVLGSLQFGY NIGVINAPQK VIEQSYNATW 70 80 90 100 110 120 LGRQGPGGPD SIPQGTLTTL WALSVAIFSV GGMISSFLIG IISQWLGRKR AMLANNVLAV 130 140 150 160 170 180 LGGALMGLAN AAASYEILIL GRFLIGAYSG LTSGLVPMYV GEIAPTHLRG ALGTLNQLAI 190 200 210 220 230 240 VIGILVAQVL GLESMLGTAT LWPLLLAITV LPALLQLLLL PFCPESPRYL YIIRNLEGPA 250 260 270 280 290 300 RKSLKRLTGW ADVSDALAEL KDEKRKLERE RPLSLLQLLG SRTHRQPLII AVVLQLSQQL 310 320 330 340 350 360 SGINAVFYYS TSIFELAGVE QPAYATIGAG VVNTVFTLVS VLLVERAGRR TLHLLGLAGM 370 380 390 400 410 420 CGCAILMTVA LLLLERVPSM SYVSIVAIFG FVAFFEIGPG PIPWFIVAEL FSQGPRPAAM 430 440 450 460 470 480 AVAGFSNWTC NFIVGMGFQY VADAMGPYVF LLFAVLLLGF FIFTFLRVPE TRGRTFDQIS 490 500 ATFRRTPSLL EQEVKPSTEL EYLGPDEND

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a novel gene encoding an insulin-responsive glucose transporter protein." Birnbaum M.J. Cell 57:305-315(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and characterization of an insulin-regulatable glucose transporter." James D.E., Strube M., Mueckler M. Nature 338:83-87(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"A glucose transport protein expressed predominately in insulin-responsive tissues." Charron M.J., Brosius F.C. III, Alper S.L., Lodish H.F. Proc. Natl. Acad. Sci. U.S.A. 86:2535-2539(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Characterization of rat Glut4 glucose transporter expressed in the yeast Saccharomyces cerevisiae: comparison with Glut1 glucose transporter." Kasahara T., Kasahara M. Biochim. Biophys. Acta 1324:111-119(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley.
[5]	"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: Heart.
[6]	"Myocyte enhancer factor 2 (MEF2) binding site is essential for C2C12 myotube-specific expression of the rat GLUT4/muscle-adipose facilitative glucose transporter gene." Liu M.L., Olson A.L., Edgington N.P., Moye-Rowley W.S., Pessin J.E. J. Biol. Chem. 269:28514-28521(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
[7]	"Characterization of 5'-heterogeneity of the rat GLUT4/muscle-adipose glucose transporter gene product." Olson A.L., Edgington N.P., Moye-Rowley W.S., Pessin J.E. Endocrinology 136:1962-1968(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-25.
[8]	"Intracellular targeting of the insulin-regulatable glucose transporter (GLUT4) is isoform specific and independent of cell type." Haney P.M., Slot J.W., Piper R.C., James D.E., Mueckler M. J. Cell Biol. 114:689-699(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC)." Foster L.J., Rudich A., Talior I., Patel N., Huang X., Furtado L.M., Bilan P.J., Mann M., Klip A. J. Proteome Res. 5:64-75(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDUFA9.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M25482 mRNA. Translation: AAA41451.1. X14771 mRNA. Translation: CAA32879.1. J04524 mRNA. Translation: AAA41453.1. D28561 mRNA. Translation: BAA05911.1. BC085757 mRNA. Translation: AAH85757.1. L36125 Genomic DNA. Translation: AAA65751.1. S77784 mRNA. No translation available.
IPI	IPI00194348.
PIR	A32101.
RefSeq	NP_036883.1. NM_012751.1.
UniGene	Rn.1314.
3D structure databases
ProteinModelPortal	P19357.
ModBase	Search...
Protein-protein interaction databases
IntAct	P19357. 633 interactions.
MINT	MINT-1775053.
STRING	10116.ENSRNOP00000023256.
PTM databases
PhosphoSite	P19357.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000023256; ENSRNOP00000023256; ENSRNOG00000017226.
GeneID	25139.
KEGG	rno:25139.
UCSC	RGD:2711. rat.
Organism-specific databases
CTD	6517.
RGD	2711. Slc2a4.
Phylogenomic databases
eggNOG	COG0477.
GeneTree	ENSGT00630000089621.
HOGENOM	HOG000202871.
HOVERGEN	HBG014816.
KO	K07191.
OrthoDB	EOG4BG8W5.
Gene expression databases
Genevestigator	P19357.
GermOnline	ENSRNOG00000017226. Rattus norvegicus.
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]
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	605563.

Entry information

Entry name

GTR4_RAT

Accession

Primary (citable) accession number: P19357
Secondary accession number(s): P97900

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program