GLUT4_BOVIN
ID GLUT4_BOVIN Reviewed; 509 AA.
AC Q27994; P79104; Q29RP5; Q6SI69;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Solute carrier family 2, facilitated glucose transporter member 4 {ECO:0000305};
DE AltName: Full=Glucose transporter type 4, insulin-responsive {ECO:0000303|PubMed:9027564};
DE Short=GLUT-4 {ECO:0000303|PubMed:9027564};
GN Name=SLC2A4 {ECO:0000250|UniProtKB:P14672};
GN Synonyms=GLUT4 {ECO:0000303|PubMed:9027564};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=White adipose tissue;
RX PubMed=9027564; DOI=10.2527/1997.751182x;
RA Abe H., Morimatsu M., Nikami H., Miyashige T., Saito M.;
RT "Molecular cloning and mRNA expression of the bovine insulin-responsive
RT glucose transporter (GLUT4).";
RL J. Anim. Sci. 75:182-188(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Korean;
RA Kang M.-J., Jeong Y.H., Lee S.M., Park H.Y., Yang J.M., Mun S.C.,
RA Yoon D.H., Kim D.M.;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Heart ventricle;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 108-187.
RC TISSUE=Muscle;
RX PubMed=8925410; DOI=10.1016/1357-2725(96)00013-1;
RA Hocquette J.F., Graulet B., Castiglia-Delavaud C., Bornes F., Lepetit N.,
RA Ferre P.;
RT "Insulin-sensitive glucose transporter transcript levels in calf muscles
RT assessed with a bovine GLUT4 cDNA fragment.";
RL Int. J. Biochem. Cell Biol. 28:795-806(1996).
CC -!- FUNCTION: Insulin-regulated facilitative glucose transporter, which
CC plays a key role in removal of glucose from circulation. Response to
CC insulin is regulated by its intracellular localization: in the absence
CC of insulin, it is efficiently retained intracellularly within storage
CC compartments in muscle and fat cells. Upon insulin stimulation,
CC translocates from these compartments to the cell surface where it
CC transports glucose from the extracellular milieu into the cell.
CC {ECO:0000250|UniProtKB:P19357}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose(out) = D-glucose(in); Xref=Rhea:RHEA:60376,
CC ChEBI:CHEBI:4167; Evidence={ECO:0000250|UniProtKB:P19357};
CC -!- SUBUNIT: Binds to DAXX. Interacts via its N-terminus with SRFBP1 (By
CC similarity). Interacts with NDUFA9 (By similarity). Interacts with
CC TRARG1; the interaction is required for proper SLC2A4 recycling after
CC insulin stimulation (By similarity). {ECO:0000250|UniProtKB:P14142,
CC ECO:0000250|UniProtKB:P14672, ECO:0000250|UniProtKB:P19357}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P14142};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P14142}.
CC Endomembrane system {ECO:0000250|UniProtKB:P14142}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P14142}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P14142}. Note=Localizes primarily to the
CC perinuclear region, undergoing continued recycling to the plasma
CC membrane where it is rapidly reinternalized (By similarity). The
CC dileucine internalization motif is critical for intracellular
CC sequestration (By similarity). Insulin stimulation induces
CC translocation to the cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:P14142, ECO:0000250|UniProtKB:P14672}.
CC -!- DOMAIN: The dileucine internalization motif is critical for
CC intracellular sequestration. {ECO:0000250|UniProtKB:P14672}.
CC -!- PTM: Sumoylated. {ECO:0000250|UniProtKB:P14672}.
CC -!- PTM: Palmitoylated. Palmitoylation by ZDHHC7 controls the insulin-
CC dependent translocation of GLUT4 to the plasma membrane.
CC {ECO:0000250|UniProtKB:P14672}.
CC -!- MISCELLANEOUS: Insulin-stimulated phosphorylation of TBC1D4 is required
CC for GLUT4 translocation. {ECO:0000250|UniProtKB:P14142}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. Sugar
CC transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D63150; BAA21105.1; -; mRNA.
DR EMBL; AY458600; AAR24285.1; -; mRNA.
DR EMBL; BC114082; AAI14083.1; -; mRNA.
DR EMBL; U18105; AAB04950.1; -; mRNA.
DR RefSeq; NP_777029.1; NM_174604.1.
DR AlphaFoldDB; Q27994; -.
DR SMR; Q27994; -.
DR STRING; 9913.ENSBTAP00000012109; -.
DR PaxDb; Q27994; -.
DR Ensembl; ENSBTAT00000012109; ENSBTAP00000012109; ENSBTAG00000009190.
DR GeneID; 282359; -.
DR KEGG; bta:282359; -.
DR CTD; 6517; -.
DR VEuPathDB; HostDB:ENSBTAG00000009190; -.
DR VGNC; VGNC:34801; SLC2A4.
DR eggNOG; KOG0569; Eukaryota.
DR GeneTree; ENSGT00940000160688; -.
DR HOGENOM; CLU_001265_30_5_1; -.
DR InParanoid; Q27994; -.
DR OMA; KVQWRFF; -.
DR OrthoDB; 749998at2759; -.
DR TreeFam; TF313762; -.
DR Reactome; R-BTA-189200; Cellular hexose transport.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000009190; Expressed in choroid plexus and 96 other tissues.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0012505; C:endomembrane system; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:0032593; C:insulin-responsive compartment; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IEA:Ensembl.
DR GO; GO:0005355; F:glucose transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015304; F:glucose uniporter activity; ISS:UniProtKB.
DR GO; GO:0015149; F:hexose transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0010021; P:amylopectin biosynthetic process; IEA:Ensembl.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0044381; P:glucose import in response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:1904659; P:glucose transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015749; P:monosaccharide transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
DR InterPro; IPR002441; Glc_transpt_4.
DR InterPro; IPR045263; GLUT.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR003663; Sugar/inositol_transpt.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR PANTHER; PTHR23503; PTHR23503; 1.
DR Pfam; PF00083; Sugar_tr; 1.
DR PRINTS; PR01193; GLUCTRSPORT4.
DR PRINTS; PR00171; SUGRTRNSPORT.
DR SUPFAM; SSF103473; SSF103473; 1.
DR TIGRFAMs; TIGR00879; SP; 1.
DR PROSITE; PS50850; MFS; 1.
DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 1.
DR PROSITE; PS00217; SUGAR_TRANSPORT_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Reference proteome; Sugar transport; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..509
FT /note="Solute carrier family 2, facilitated glucose
FT transporter member 4"
FT /id="PRO_0000050361"
FT TOPO_DOM 1..24
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..81
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..111
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 112..132
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..142
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 193..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..287
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 288..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..323
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..344
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 345..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 354..374
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 375..384
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 418..438
FT /note="Helical; Name=11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..445
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 446..466
FT /note="Helical; Name=12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 467..509
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 7..13
FT /note="Interaction with SRFBP1"
FT /evidence="ECO:0000250|UniProtKB:P14672"
FT MOTIF 489..490
FT /note="Dileucine internalization motif"
FT /evidence="ECO:0000255"
FT BINDING 177
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT BINDING 298..299
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT BINDING 304
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT BINDING 333
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT BINDING 396
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT BINDING 404
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /evidence="ECO:0000250|UniProtKB:P11169"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19357"
FT MOD_RES 274
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:P14672"
FT MOD_RES 486
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14142"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14142"
FT LIPID 223
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P14672"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 27
FT /note="A -> G (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="N -> S (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="V -> D (in Ref. 4; AAB04950)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="P -> S (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="V -> M (in Ref. 2; AAR24285)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="R -> H (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="G -> A (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
FT CONFLICT 404
FT /note="W -> C (in Ref. 1; BAA21105)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 55084 MW; D5BC14E2B78B4D01 CRC64;
MPSGFQQIGS EDGEPPRQRV TGTLVLAVFS AVLGSLQFGY NIGVINAPQK VIEQSYNETW
LGRQGPEGPG SIPPGTLTTL WALSVAIFSV GGMISSFLIG IISQWLGRKR AMLFNNALAV
LGGTLMGLAK AAASYEMLIL GRFFIGAYSG LTSGLVPMYV GEIAPTHLRG ALGTLNQLAI
VTGILIAQVL GLESMLGTAT LWPLLLGITV LPALLQMVLL PLCPESPRYL YIIRNLEGPA
RKSLKRLTGW ADVSEVLAEL KEEKRKLERE RPLSLLQLLG SHTHRQPLVI AIVLQLSQQL
SGINAVFYYS TSIFESAGVE KPAYATIGAG VVNTVFTLVS VFLVERAGRR TLHLLGLAGM
CGCAILMTVA LLLLERVPAM SYVSIVAIFG FVAFFEIGPG PIPWFIVAEL FSQGPRPAAM
AVAGFSNWTC NFIIGMGFQY VADAMGPYVF LLFAVLLLGF FIFTFLKVPE TRGRTFDQIS
AVFHRTPSLL EQEVKPSTEL EYLGPDEHD
