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Symbol SLC2A4 contributors: mct - updated : 22-06-2016
HGNC name solute carrier family 2 (facilitated glucose transporter), member 4
HGNC id 11009
Location 17p13.1      Physical location : 7.185.053 - 7.191.366
Synonym name
  • glucose transporter 4, insuline-responsive
  • insulin-responsive glucose transporter type 4
  • Synonym symbol(s) GLUT4
    TYPE functioning gene
    STRUCTURE 6.31 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer   transcription factor   HRE
    text structure
  • promoter regulated through the cooperative function of two distinct regulatory elements SLC2A4RG and MEF2A
  • an Sp1 binding site adjacent to the functional sterol-response element
  • two kappaB sites in SLC2a4 gene promote, and NFKB1 has a direct repressor effect upon the SLC2A4 gene, providing an important link between insulin resistance and inflammation
  • MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3159 - 509 - 2014 25025572
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Respiratoryrespiratory tractlarynx  highly
    Visualeyeretina    Rattus norvegicus
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly Homo sapiens
    Muscularstriatumskeletal highly Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Visualcone photoreceptor Rattus norvegicus
    Visualganglion cell Rattus norvegicus
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
  • twelve putative transmembrane segments (12TM)
  • intracellular N and C termini
  • a large extracellular loop, with first intracellular loop of GLUT4 containing the retention motif WLGRK, in which W105 plays a prominent role
  • a glycosylation site between TM1 and 2
  • a small and a large intracellular loops, respectively between TM2 and 3 and TM8 and 9, both with the conserved RXGRR motif
  • major facilitator superfamily
  • sugar transporter family
  • glucose transporter subfamily
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • stimulation of glucose uptake by insulin requires translocation of SLC24A to intracellular storage sites to cell surface
  • AXIN1, TNKS2 and KIF3A are co-localized with SLC2A4 on the trans-Golgi network
  • reduced SLC2A4 translocation from intracellular storage compartments to the plasma membrane is a cause of peripheral insulin resistance
  • basic FUNCTION
  • facilitated glucose transporter
  • mediating insulin-stimulated glucose uptake in adipocytes and muscle by rapidly moving from intracellular storage sites to the plasma membrane
  • specific role in glucose homeostasis in conjunction with LNPEP
  • mediating the postprandial blood glucose clearance
  • role for LNPEP and SLC2A4 in activity-dependent glucose uptake in hippocampal neurones
  • dynamically retained through idle cycling among selective intracellular compartments, from whence it undergoes slow recycling to the plasma membrane (PM)
  • cardiac glucose utilization is regulated by reversible translocation of the glucose transporter SLC2A4 from intracellular stores to the plasma membrane
  • facilitates insulin-stimulated glucose uptake in peripheral tissues including adipose, muscle, and heart
  • SLC2A4 and SLC2A8 trafficking is impaired in the diabetic atria and rescued by insulin treatment
  • plays a major role in glucose homeostasis and is efficiently retained intracellularly in adipocytes and myocytes
    PHYSIOLOGICAL PROCESS facilitated diffusion transport
    metabolism carbohydrate
    a component
  • C-ter is required for protein targeting to the perinuclear donor membranes but not to the insulin-responsive vesicles
    small molecule metal binding,
  • CaČ&
  • 8314; signals promote SLC2A4 exocytosis and reduce its endocytosis in muscle cells
  • SLC2A4RG and MEF2A to activate SLC2A4 transcription
  • interacting with SGK1 (stimulates glucose transport by enhancing the abundance of SLC2A4 in the cell membrane at least in part via direct SLC2A4 phosphorylation)
  • interacting with TBC1D4
  • interacting with VAMP4, VAMP8, VAMP2 (requirement for VAMP4 for the initial biosynthetic entry of SLC2A4 from the Golgi apparatus into the insulin-responsive vesicle compartment, VAMP8, for plasma membrane endocytosis and VAMP2 for sorting to the specialized insulin-responsive compartment after plasma membrane endocytosis)
  • ARFRP1 appears to be involved in sorting of SLC2A4
  • AXIN1 interacts with the ADP-ribosylase tankyrase 2 (TNKS2) and the kinesin motor protein KIF3A, forming a ternary complex crucial for SLC2A4 translocation in response to insulin
  • RAB10 is likely involved in insulin-stimulated translocation of SLC2A4 storage vesicle (GSV) to the Plasma membrane, with RAB14 involved in insulin-stimulated translocation of SLC2A4-containing endosome
  • insulin promotes SLC2A4 exocytosis by regulating SLC2A4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion with the plasma membrane
  • interaction of vesicular MYO1C with cortical actin filaments is required for insulin-mediated tethering of SLC2A4 vesicles and for efficient SLC2A4 surface delivery in muscle cells
  • VAMP3, is able to protect insulin-stimulated SLC2A4 translocation during early stages of diet-induced insulin resistance and preserves normal CD36 distribution
  • DNAJC5 is involved in insulin resistance by interrupting SLC2A4 vesicle docking with the plasma membrane
  • BCAR3 plays an important role in the signaling pathways of insulin leading to cell cycle progression and cytoskeleton reorganization, but not SLC2A4 translocation
  • RAB5A activity regulates SLC2A4 sorting into insulin-responsive and non-insulin-responsive endosomal compartments: a potential mechanism for development of insulin resistance
  • SIK2 increases SLC2A4 levels, regulates CRTC2, CRTC3, HDAC4 and glucose uptake in adipocytes
  • ZNF407 regulates insulin-stimulated glucose uptake and glucose transporter 4 (SLC2A4) mRNA
  • TCTEX1D2 is a novel STX4 binding protein that functions as a negative regulator of SLC2A4 plasma membrane translocation (pMID: 26200093)
  • TMOD3 is a novel AKT2 effector regulating insulin-stimulated SLC2A4 exocytosis through cortical actin remodeling
  • TBC1D4 (AS160) controls trafficking of the glucose transporter SLC2A4 in adipocytes and skeletal muscle cells
  • transcription factor MEF2A and PLAGL1 mediate MIF-induced SLC2A4 expression through CD74-dependent AMPK activation in cardiomyocytes
  • SLC2A4 traffics predominantly through the specialized RAB10-dependent pathway both before and after insulin stimulation
  • RAB10 is a regulator of insulin-stimulated translocation of the SLC2A4 glucose transporter to the plasma membrane (PM) of adipocytes, which is essential for whole-body glucose homeostasis
  • cell & other
    Other translocated to plasma membrane for insulin stimulated glucose uptake,requiring activation of phosphatidylinositol-3-OH kinase (PI(3)K) and activation of TC10 (essential)
    may be regulated by PLAGL1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in adipose tissue but preserved in muscle in insuline-resitant states such as obesity and type 2 diabetes
    Susceptibility non insulin dependent diabetes mellitus (type 2)
    Variant & Polymorphism polymorphic variant
    Candidate gene
    Therapy target
    diabetetype 2 
    promising target for pharmacogenomics of insulin resistance
    therapeutic strategy entailing selective SLC2A4, SLC2A11, SLC2A8 inhibition to specifically target aberrant glucose metabolism in cancer
    G4A -/- mice