P14142 (GTR4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 2, facilitated glucose transporter member 4

Alternative name(s):
GT2
Glucose transporter type 4, insulin-responsive
Short name=GLUT-4

Gene names

Name:	Slc2a4
Synonyms:	Glut-4, Glut4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

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. Interacts with NDUFA9 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. 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.11
Tissue specificity	Skeletal and cardiac muscles; brown and white fat.
Involvement in disease	Defects in Slc2a4 may be the cause of certain post-receptor defects in non-insulin-dependent diabetes mellitus (NIDDM).
Miscellaneous	Insulin-stimulated phosphorylation of TBC1D4 is required for GLUT4 translocation.
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
Disease	Diabetes mellitus
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amylopectin biosynthetic process Inferred from direct assay PubMed 14562105. Source: MGI brown fat cell differentiation Inferred from direct assay PubMed 18492766. Source: MGI cellular response to insulin stimulus Inferred from direct assay Ref.11. Source: UniProtKB cellular response to osmotic stress Inferred from direct assay PubMed 18227281. Source: MGI glucose homeostasis Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara
Cellular_component	coated pit Inferred from electronic annotation. Source: Compara cytoplasmic vesicle membrane Inferred from direct assay PubMed 12490950. Source: MGI endosome Inferred from direct assay PubMed 15247266. Source: MGI external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular vesicular exosome Inferred from direct assay PubMed 19724054. Source: MGI insulin-responsive compartment Inferred from direct assay Ref.11. Source: UniProtKB integral to plasma membrane Inferred from direct assay PubMed 14562105. Source: MGI multivesicular body Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from direct assay PubMed 10444069PubMed 15800058. Source: MGI sarcolemma Inferred from direct assay PubMed 16455755. Source: MGI trans-Golgi network transport vesicle Inferred from direct assay PubMed 17003038. Source: MGI
Molecular_function	D-glucose transmembrane transporter activity Inferred from electronic annotation. Source: Compara insulin-responsive hydrogen:glucose symporter activity Traceable author statement PubMed 7675081. Source: MGI
Complete GO annotation...

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_0000050364
Regions
	Topological domain	1 – 23	23	Cytoplasmic Potential
	Transmembrane	24 – 44	21	Helical; Name=1; Potential
	Topological domain	45 – 80	36	Extracellular Potential
	Transmembrane	81 – 101	21	Helical; Name=2; Potential
	Topological domain	102 – 110	9	Cytoplasmic Potential
	Transmembrane	111 – 131	21	Helical; Name=3; Potential
	Topological domain	132 – 141	10	Extracellular Potential
	Transmembrane	142 – 162	21	Helical; Name=4; Potential
	Topological domain	163 – 170	8	Cytoplasmic Potential
	Transmembrane	171 – 191	21	Helical; Name=5; Potential
	Topological domain	192 – 200	9	Extracellular Potential
	Transmembrane	201 – 221	21	Helical; Name=6; Potential
	Topological domain	222 – 286	65	Cytoplasmic Potential
	Transmembrane	287 – 307	21	Helical; Name=7; Potential
	Topological domain	308 – 322	15	Extracellular Potential
	Transmembrane	323 – 343	21	Helical; Name=8; Potential
	Topological domain	344 – 352	9	Cytoplasmic Potential
	Transmembrane	353 – 373	21	Helical; Name=9; Potential
	Topological domain	374 – 384	11	Extracellular Potential
	Transmembrane	385 – 405	21	Helical; Name=10; Potential
	Topological domain	406 – 416	11	Cytoplasmic Potential
	Transmembrane	417 – 437	21	Helical; Name=11; Potential
	Topological domain	438 – 444	7	Extracellular Potential
	Transmembrane	445 – 465	21	Helical; Name=12; Potential
	Topological domain	466 – 508	43	Cytoplasmic Potential
	Region	7 – 13	7	SRFBP1-binding By similarity
	Region	294 – 296	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 Ref.9
	Glycosylation	57	1	N-linked (GlcNAc...) Ref.10
Experimental info
	Sequence conflict	11	1	D → DVK in AAA37753. Ref.1
	Sequence conflict	132	1	A → V in AAA37753. Ref.1
	Sequence conflict	177	1	Q → R in AAA37753. Ref.1
	Sequence conflict	246	1	R → P in AAA37753. Ref.1
	Sequence conflict	406	1	Missing in AAA37753. Ref.1
	Sequence conflict	444	1	A → R in AAA37753. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P14142 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: A174212455EE0390	FASTA	509	54,755
	10 20 30 40 50 60 MPSGFQQIGS DDGEPPRQRV 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 LWPLLLALTV LPALLQLILL PFCPESPRYL YIIRNLEGPA 250 260 270 280 290 300 RKSLKRLTGW ADVSDALAEL KDEKRKLERE RPMSLLQLLG SRTHRQPLII AVVLQLSQQL 310 320 330 340 350 360 SGINAVFYYS TSIFESAGVG QPAYATIGAG VVNTVFTLVS VLLVERAGRR TLHLLGLAGM 370 380 390 400 410 420 CGCAILMTVA LLLLERVPAM SYVSIVAIFG FVAFFEIGPG PIPWFIVAEL FSQGPRPAAM 430 440 450 460 470 480 AVAGFSNWTC NFIVGMGFQY VADAMGPYVF LLFAVLLLGF FIFTFLKVPE TRGRTFDQIS 490 500 AAFRRTPSLL EQEVKPSTEL EYLGPDEND

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes." Kaestner K.H., Christy R.J., McLenithan J.C., Braiterman L.T., Cornelius P., Pekala P.H., Lane M.D. Proc. Natl. Acad. Sci. U.S.A. 86:3150-3154(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of type II diabetes; NSY mouse." Ueda H., Ikegami H., Kawaguchi Y., Fujisawa T., Nojima K., Babaya N., Yamada K., Shibata M., Yamato E., Ogihara T. Diabetologia 43:932-938(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C3H and NSY. Tissue: Muscle.
[3]	"Characterization of quantitative trait loci influencing growth and adiposity using congenic mouse strains." Farber C.R., Corva P.M., Medrano J.F. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: CAST/EiJ. Tissue: Brain.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Bone and Spinal ganglion.
[5]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[6]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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.
[8]	"Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation." Sano H., Kane S., Sano E., Miinea C.P., Asara J.M., Lane W.S., Garner C.W., Lienhard G.E. J. Biol. Chem. 278:14599-14602(2003) [PubMed] [Europe PMC] [Abstract] Cited for: EFFECT OF TBC1D4 ON GLUT4 TRANSLOCATION.
[9]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-488, MASS SPECTROMETRY. Tissue: Melanoma.
[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, MASS SPECTROMETRY.
[11]	"C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane." Xie X., Gong Z., Mansuy-Aubert V., Zhou Q.L., Tatulian S.A., Sehrt D., Gnad F., Brill L.M., Motamedchaboki K., Chen Y., Czech M.P., Mann M., Kruger M., Jiang Z.Y. Cell Metab. 14:378-389(2011) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M23383 mRNA. Translation: AAA37753.1. AB008453 mRNA. Translation: BAB03251.1. AY902342 Genomic DNA. Translation: AAX90627.1. AK137607 mRNA. Translation: BAE23429.1. AK164310 mRNA. Translation: BAE37730.1. AL596185 Genomic DNA. Translation: CAI35157.1. CH466596 Genomic DNA. Translation: EDL12494.1. CH466596 Genomic DNA. Translation: EDL12496.1. BC014282 mRNA. Translation: AAH14282.1.
IPI	IPI00762242.
PIR	B30310.
RefSeq	NP_033230.2. NM_009204.2.
UniGene	Mm.10661.
3D structure databases
ProteinModelPortal	P14142.
SMR	P14142. Positions 31-481.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-42440N.
MINT	MINT-1342290.
PTM databases
PhosphoSite	P14142.
Proteomic databases
PaxDb	P14142.
PRIDE	P14142.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000018710; ENSMUSP00000018710; ENSMUSG00000018566.
GeneID	20528.
KEGG	mmu:20528.
Organism-specific databases
CTD	6517.
MGI	MGI:95758. Slc2a4.
Phylogenomic databases
eggNOG	COG0477.
GeneTree	ENSGT00630000089621.
HOGENOM	HOG000202871.
HOVERGEN	HBG014816.
InParanoid	Q3TPK6.
KO	K07191.
OMA	KRAMLAN.
OrthoDB	EOG4BG8W5.
Enzyme and pathway databases
Reactome	REACT_147847. Translocation of Glut4 to the Plasma Membrane. REACT_88307. Membrane Trafficking.
Gene expression databases
Bgee	P14142.
Genevestigator	P14142.
GermOnline	ENSMUSG00000018566. Mus musculus.
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
ChEMBL	CHEMBL1250410.
NextBio	298775.
SOURCE	Search...

Entry information

Entry name

GTR4_MOUSE

Accession

Primary (citable) accession number: P14142
Secondary accession number(s): Q3TPK6, Q9JJN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 134 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program