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Showing SLC2A5 — GLUT5 is a alias.

SLC2A5

Solute carrier family 2, facilitated glucose transporter member 5 · UniProt P22732

Length
501 aa
Mass
55.0 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC2A5/GLUT5 is a plasma-membrane fructose transporter of the major facilitator superfamily that mediates cytochalasin B-insensitive, high-affinity facilitated diffusion of D-fructose (Km ~6–15 mM) but not glucose, providing the rate-limiting entry step for fructose into intestinal, renal, muscle, adipocyte, and erythrocyte tissues (PMID:1634504, PMID:8333543, PMID:9299540, PMID:9166863). Crystal structures captured in outward- and inward-facing states reveal a rocker-switch transport cycle gated by local rearrangements of the TM7 and TM10 helices, and a single point mutation is sufficient to switch GLUT5 substrate preference between fructose and glucose, defining how a small set of residues across the first extracellular loop, TM5, and TM7–TM10 dictates strict fructose selectivity and furanose-form, stereochemically defined recognition (PMID:26416735, PMID:26306809, PMID:29259131, PMID:28205432). GLUT5 localizes constitutively to the apical brush-border membrane of enterocytes and renal proximal tubule cells and to the sarcolemma and adipocyte plasma membrane independently of insulin-stimulated translocation (PMID:1550217, PMID:10469370, PMID:9686924, PMID:1397712). Its expression is induced specifically by luminal fructose through a transcriptional and post-transcriptional program involving glucocorticoid receptor nuclear translocation and binding to the Glut5 promoter, histone H3 acetylation and Pol II recruitment, thyroid hormone receptor and LXRα response elements, and cAMP-dependent mRNA stabilization (PMID:9486174, PMID:21222652, PMID:18556366, PMID:10191252, PMID:31243309, PMID:12820898). Physiologically, GLUT5 is required for intestinal fructose absorption and feed-forward induction of fructolytic enzymes upstream of ketohexokinase, and its loss prevents fructose-induced hypertension and alters microbiota-dependent colitis (PMID:26084694, PMID:18496516, PMID:34133236). In cancer, GLUT5-mediated fructose uptake is sufficient to support fructose-dependent proliferation through hexokinase-driven glycolysis and drives migration and metastasis via a glycolysis/lactate/AKT axis and mitochondrial remodeling, with its expression controlled by IL-6/STAT3, AKT/miR-125b-5p, S100P-mediated promoter demethylation, and SNAI1/SNAI2 repression (PMID:33762003, PMID:36454516, PMID:36268513, PMID:35813468, PMID:32649737, PMID:34188196).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    Established the fundamental identity of GLUT5 as a fructose-selective transporter, distinguishing it functionally from the glucose-transporting GLUTs.

    Evidence Heterologous expression of human GLUT5 in Xenopus oocytes with radiolabeled sugar uptake and cytochalasin B inhibition studies

    PMID:1634504

    Open questions at the time
    • Did not resolve the structural basis of fructose selectivity
    • Did not address tissue-specific physiological roles
  2. 1992 High

    Defined where GLUT5 acts in tissue, showing apical brush-border localization in enterocytes and developmental regulation of its targeting.

    Evidence Immunohistochemistry and Western blot of purified brush-border membranes from adult and fetal human intestine

    PMID:1397712 PMID:1530566 PMID:1550217

    Open questions at the time
    • Mechanism of apical targeting not defined
    • Whether basolateral pools exist not resolved at this stage
  3. 1992 Medium

    Showed GLUT5 is a constitutive, non-insulin-responsive transporter, contrasting it with insulin-regulated GLUT4.

    Evidence Subcellular fractionation of adipocytes with/without insulin plus cytochalasin B photolabeling

    PMID:1397712 PMID:9686924

    Open questions at the time
    • Single-lab fractionation
    • Did not exclude longer-term transcriptional insulin effects later observed in muscle
  4. 1995 High

    Began mapping the protein determinants of fructose transport using chimeric transporters, localizing function to the N-terminal half and C-terminal region.

    Evidence GLUT1/GLUT5 and GLUT5/GLUT3 chimeric protein expression in CHO cells and oocytes with sugar uptake assays

    PMID:7588216 PMID:9492009

    Open questions at the time
    • Resolution limited to large domains, not individual residues
    • No structural model available
  5. 1997 High

    Refined the substrate-recognition profile, showing GLUT5 transports D-fructose in the furanose form across a broad pH range.

    Evidence Xenopus oocyte expression with sugar analogue inhibition and pH variation

    PMID:7980458 PMID:9299540

    Open questions at the time
    • Residues mediating furanose recognition not identified
    • No co-structure with substrate
  6. 1998 High

    Demonstrated that luminal fructose, not endocrine signals, drives intestinal GLUT5 induction, establishing substrate-sensing as the regulatory input.

    Evidence Thiry-Vella intestinal bypass surgery in weaning rats with transport and Northern blot readout

    PMID:9124564 PMID:9486174

    Open questions at the time
    • Molecular sensor of luminal fructose not identified
    • Did not connect signal to specific promoter elements
  7. 2003 Medium

    Resolved a post-transcriptional arm of GLUT5 regulation, linking cAMP to GLUT5 mRNA stability via 3'-UTR RNA-protein complexes.

    Evidence mRNA half-life measurement, PKA inhibition, RNA-protein binding assays identifying Paip2 in Caco-2 cells

    PMID:12820898 PMID:8037665 PMID:8554516

    Open questions at the time
    • Direct functional role of Paip2 in destabilization not validated by depletion
    • Single lab
  8. 2011 High

    Connected fructose sensing to the chromatin level, showing GR nuclear translocation, promoter binding, and histone acetylation drive developmental GLUT5 induction.

    Evidence ChIP for Pol II, GR, and histone acetylation marks in perfused rat intestine of defined ages

    PMID:17947353 PMID:18556366 PMID:21222652

    Open questions at the time
    • How fructose signal reaches GR not defined
    • Histone acetyltransferase responsible not identified
  9. 2015 High

    Provided the atomic-resolution mechanism, capturing outward- and inward-facing states and showing a single residue switches fructose-versus-glucose preference.

    Evidence X-ray crystallography of rat and bovine GLUT5 in two conformations plus point-mutation functional analysis

    PMID:26306809 PMID:26416735 PMID:29259131

    Open questions at the time
    • No substrate-bound human structure
    • Conformational transition dynamics inferred, not directly observed
  10. 2015 High

    Placed GLUT5 upstream in a feed-forward fructose-sensing pathway required for fructolytic and gluconeogenic enzyme induction.

    Evidence GLUT5-KO, KHK-KO, and Rab11a-KO mice with dietary fructose gavage and gene expression readout

    PMID:18496516 PMID:26084694

    Open questions at the time
    • Identity of the intracellular fructose-sensing signal not pinned down
    • Tissue specificity of feed-forward loop beyond intestine unclear
  11. 2019 High

    Expanded the transcriptional control network by identifying functional thyroid hormone receptor and LXRα response elements in the GLUT5 promoter.

    Evidence Promoter truncation and mutagenesis reporter assays, EMSA, and in vivo agonist treatment in mice

    PMID:10191252 PMID:31243309

    Open questions at the time
    • Integration of multiple promoter inputs not modeled
    • Physiological context where each factor dominates unclear
  12. 2021 High

    Demonstrated GLUT5-mediated fructose uptake is the limiting and sufficient step for fructose-dependent cancer cell proliferation, routed through hexokinase rather than ketohexokinase.

    Evidence Lentiviral GLUT5 overexpression and KHK CRISPR-KO across multiple cell lines with metabolic flux and metabolomics

    PMID:32649737 PMID:33762003 PMID:34188196 PMID:35813468

    Open questions at the time
    • Cell-type determinants of HK-versus-KHK routing not fully defined
    • In vivo tumor dependence on dietary fructose not addressed here
  13. 2022 Medium

    Linked GLUT5 fructose metabolism to malignant migration and metastasis via a glycolysis/lactate/AKT axis and mitochondrial remodeling.

    Evidence CRISPR SLC2A5 deletion plus overexpression with migration assays, AKT phosphorylation, pharmacological inhibition, and tail-vein metastasis models

    PMID:32649737 PMID:36268513 PMID:36454516

    Open questions at the time
    • Mechanism linking fructose metabolism to mitochondrial architecture not resolved
    • Single lab for each model system
  14. 2023 Medium

    Provided a dynamic mechanistic refinement, showing fructose binding lowers transition barriers and that allosteric TM7b gating, not the binding site alone, confers selectivity.

    Evidence Enhanced-sampling molecular dynamics simulations validated against biochemical transport data

    PMID:37405832

    Open questions at the time
    • Computational prediction lacks direct structural snapshot of the occluded state
    • Human transporter dynamics inferred from model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple promoter inputs (GR, THR, LXRα, STAT3, S100P, SNAI1/2), post-transcriptional control, and the luminal fructose-sensing signal are integrated to set GLUT5 levels in a given cell context remains unresolved.
  • No unified model of combinatorial GLUT5 transcriptional regulation
  • The proximal fructose sensor upstream of these factors is unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0005198 structural molecule activity 1
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2
Partners
PAIP2PRESTINSLC26A6

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 GLUT5 (SLC2A5) functions as a high-affinity fructose transporter with a Km of 6 mM, exhibits selectivity for fructose over glucose, and is not inhibited by cytochalasin B (a competitive inhibitor of other facilitative glucose transporters). Established by expression of human GLUT5 mRNA in Xenopus oocytes with inhibition studies. Xenopus oocyte expression system, radiolabeled sugar uptake assays, inhibition studies with cytochalasin B The Journal of biological chemistry High 1634504
1992 GLUT5 protein is localized to the luminal (brush border) membrane of mature enterocytes in adult human small intestine, while in fetal small intestine it is found along intercellular junctions of developing villi, indicating developmental regulation of both expression and localization. Immunohistochemistry, Western blot of purified brush-border membranes The American journal of physiology High 1550217
1992 GLUT5 is localized exclusively to the plasma membrane of human skeletal muscle cells, as demonstrated by subcellular fractionation showing enrichment in plasma-membrane fraction with minimal intracellular localization (~10%), confirmed by immunofluorescence. Subcellular fractionation, Western blot, immunofluorescence on cryostat sections The Biochemical journal Medium 1530566
1992 GLUT5 is expressed in human small intestine, kidney, heart, skeletal muscle, brain, and adipocyte plasma membranes. Insulin does not stimulate translocation of GLUT5 to the plasma membrane in adipocytes, indicating GLUT5 is a constitutive (non-insulin-responsive) sugar transporter. Immunoblotting, cytochalasin B photolabeling, immunoprecipitation, subcellular fractionation of adipocytes with/without insulin Diabetes Medium 1397712
1993 Rat GLUT5 expressed in Xenopus oocytes mediates uptake of fructose and, to a lesser extent, glucose. GLUT5 mRNA is developmentally regulated, with low prenatal levels and rapid postnatal induction in rat small intestine and kidney. Xenopus oocyte expression, radiolabeled sugar uptake, Northern blot, in situ hybridization The American journal of physiology High 8333543
1994 Cyclic AMP (cAMP) increases GLUT5 expression in Caco-2 cells by both stabilizing GLUT5 mRNA and increasing transcription, as demonstrated by forskolin treatment raising GLUT5 protein 5-fold and mRNA 7-fold, and by GLUT5 promoter-reporter gene assays showing cis-acting regulatory sequences mediate the effect. Forskolin treatment of differentiated Caco-2 cells, Northern/Western blot, GLUT5 promoter-reporter (luciferase) transfection assays The Biochemical journal Medium 8037665
1994 Rabbit GLUT5 expressed in Xenopus oocytes mediates fructose transport with a Km of 11 mM. D-fructose transport by GLUT5 is inhibited by D-glucose and D-galactose in oocytes, and cytochalasin B photolabels GLUT5 in brush-border membrane preparations. GLUT5 is localized to the brush-border membrane of rabbit intestinal epithelial cells. Xenopus oocyte expression, radiolabeled fructose uptake, hybrid depletion with antisense oligonucleotide, immunoblot, cytochalasin B photolabeling, immunoprecipitation The Biochemical journal High 7980458
1995 GLUT5 is present not only in the brush-border membrane (BBM) but also in the basolateral membrane (BLM) of the human jejunum, with near-equal amounts per mg membrane protein in both fractions. Immunogold electron microscopy confirmed GLUT5 at both apical and basolateral membranes. Subcellular fractionation, quantitative immunoblotting, immunogold electron microscopy The Biochemical journal High 7619085
1995 Rat GLUT5 expressed in CHO cells is targeted exclusively to the plasma membrane and transports fructose (Km = 11.6 mM) but not glucose, and is not photolabeled by cytochalasin B. Chimeric GLUT1/GLUT5 analysis showed that the intracellular middle loop and TM7-12 region are critical for GLUT1 glucose transport, while both the N-terminal half (including TM1-6) and the intracellular C-terminal region are required for GLUT5 fructose transport. Transfection into CHO cells, radiolabeled sugar uptake, cytochalasin B photolabeling, chimeric protein expression in Xenopus oocytes Endocrinology High 7588216
1995 Fructose and glucose both increase GLUT5 expression in Caco-2 cells, with fructose being a stronger inducer (3-fold higher GLUT5 protein and mRNA vs. glucose). cAMP levels show a linear correlation with GLUT5 mRNA abundance in hexose-deprived cells, implicating cAMP signaling in sugar-induced GLUT5 regulation. Cell culture with defined sugar media, Northern/Western blot, cAMP measurement The Biochemical journal Medium 8554516
1997 Human GLUT5 expressed in Xenopus oocytes functions exclusively as a D-fructose transporter between pH 4.5 and 8.0 (Km ~15 mM at pH 7.5). Analysis with sugar analogues indicates GLUT5 preferentially transports D-fructose in the furanose ring form. Xenopus oocyte expression, radiolabeled sugar uptake, pH variation, sugar analogue inhibition studies Biochemical and biophysical research communications High 9299540
1997 Human erythrocytes express GLUT5, which is the predominant transporter mediating fructose entry with an apparent Km ~10 mM. This transport is insensitive to 2-deoxy-D-glucose and cytochalasin B (which inhibit GLUT1/GLUT2), functionally distinguishing GLUT5-mediated fructose transport from other hexose transporters. Immunoblotting, immunolocalization, kinetic fructose transport studies, inhibitor studies in isolated erythrocytes Blood Medium 9166863
1997 Dietary fructose specifically enhances brush-border fructose transport rates and GLUT5 mRNA levels in weaning rats. Only luminal fructose (not glucose or sucrose without fructose) induces GLUT5 expression, and the effect is dose-dependent on luminal fructose concentration. In vivo dietary supplementation, intestinal brush-border vesicle transport assays, Northern blot The American journal of physiology Medium 9124564
1998 GLUT5 is expressed in the sarcolemma of rat skeletal muscle and mediates cytochalasin B-insensitive fructose uptake. Fructose-enriched diet for 4 days increased jejunal and renal GLUT5 but had no detectable effect on GLUT5 in skeletal muscle or adipocytes, indicating tissue-specific regulation. Subcellular fractionation, immunoblot, RT-PCR, sarcolemmal vesicle fructose uptake, cytochalasin B inhibition The Biochemical journal Medium 9820812
1998 GLUT5 in rat adipocytes mediates ~80% of total fructose uptake in a cytochalasin B-insensitive manner. GLUT5 is localized only to the adipocyte plasma membrane, and its cell-surface abundance is not modulated by insulin. In streptozotocin-diabetic rats, GLUT5 expression falls ~75% accompanied by ~50% reduction in fructose uptake. Subcellular fractionation, cytochalasin B inhibition assay, immunoblot, streptozotocin diabetes model Diabetologia Medium 9686924
1998 Luminal (not endocrine) fructose signals regulate GLUT5 expression in weaning rat intestine, demonstrated by Thiry-Vella bypass surgery showing that intestinal loops lacking luminal contact with fructose had low GLUT5 mRNA and fructose transport despite systemic exposure. Thiry-Vella intestinal bypass surgery in weaning rats, radiolabeled sugar transport assays, Northern blot The American journal of physiology High 9486174
1999 GLUT5 is localized to the apical plasma membrane of brush border microvilli in S3 proximal tubule cells of rat kidney outer medullary stripe, demonstrated by high-resolution immunofluorescence and immunogold electron microscopy. Immunofluorescence, immunogold electron microscopy, RT-PCR, immunoblot Kidney international High 10469370
1999 Glucose and thyroid hormone (T3) co-regulate GLUT5 mRNA abundance in Caco-2/TC7 cells. Promoter deletion analysis localized glucose responsiveness to the -272/+41 fragment and T3 responsiveness to the -338/+41 region. EMSA demonstrated that thyroid hormone receptors α and β bind to the -308/-290 region of the GLUT5 promoter as THR/RXR heterodimers. GLUT5 promoter-luciferase reporter transfection, promoter deletion mapping, electrophoretic mobility shift assay (EMSA) The Biochemical journal High 10191252
2000 ERK, p38, and PI3-kinase signaling pathways regulate intestinal fructose transport via GLUT5 and GLUT2. The ERK pathway restrains the p38 pathway; activation of p38 (by anisomycin) stimulates transport. GLUT2 undergoes rapid trafficking to the brush-border membrane within minutes (distinct from GLUT5), and GLUT2 intrinsic activity is regulated over a 9-fold range, while GLUT5 levels show minimal change during acute stimulation. Perfused isolated rat jejunal loops with pharmacological inhibitors (PD98059, SB203580, wortmannin), sugar transport assays, immunoblot The Biochemical journal Medium 10926840
2001 Fructose-induced precocious induction of GLUT5 in weaning rat intestine requires de novo mRNA synthesis (blocked by actinomycin D) and de novo protein synthesis (blocked by cycloheximide), while glucose has no such effect. This demonstrates transcriptional and translational mechanisms underlying substrate-induced GLUT5 reprogramming. In vivo intestinal perfusion in weaning rats, actinomycin D and cycloheximide injection, radiolabeled fructose uptake, Northern blot American journal of physiology. Gastrointestinal and liver physiology Medium 11123204
2002 Mouse GLUT5 expressed in Xenopus oocytes mediates fructose transport with a Kt of 13 mM. The GLUT5 gene uses alternative transcriptional initiation sites in somatic versus germ cells. The 5' flanking region contains CdxA, USF, and SRY binding sites potentially responsible for tissue-specific and dietary fructose-dependent expression. Xenopus oocyte expression, radiolabeled fructose uptake, 5'RACE, Northern blot, genomic sequence analysis Biochimica et biophysica acta Medium 12031501
2003 Fructose increases GLUT5 mRNA stability via cAMP signaling in Caco-2 cells: fructose raises cAMP more than glucose, which correlates with GLUT5 mRNA half-life. A 140 kDa RNA-protein complex binds the GLUT5 3'-UTR more strongly in sugar-deprived cells; PABP-interacting protein 2 (Paip2), a destabilizing partner of PABP, was identified as a component of GLUT5 3'-UTR RNA-protein complexes. GLUT5 promoter-reporter assay, PKA inhibitor treatment, mRNA half-life measurement, RNA-protein binding assays, protein identification The Biochemical journal Medium 12820898
2003 Long-term (24 h) insulin treatment of L6 skeletal muscle cells induces a dose-dependent ~2-fold increase in GLUT5 protein and fructose uptake. This effect is suppressed by inhibitors of transcription and protein synthesis, and insulin increases GLUT5 promoter activity ~1.8-fold, indicating de novo transcriptional induction. L6 cell culture with insulin treatment, Western blot, fructose uptake assay, GLUT5 promoter-luciferase transfection, inhibitor studies FEBS letters Medium 12914929
2007 Dexamethasone (a glucocorticoid) sensitizes the neonatal rat intestine to fructose-induced GLUT5 induction. Dexamethasone alone before weaning (when pups are <14 days) allows luminal fructose to precociously stimulate GLUT5 expression and fructose absorption. This age-dependent sensitization is specific to GLUT5 and does not affect SGLT1 or GLUT2. In vivo rat intestinal perfusion model, dexamethasone IP injection in neonatal rats, microarray hybridization, radiolabeled fructose uptake Endocrinology Medium 17947353
2008 Glucocorticoid receptor (GR) mediates dexamethasone sensitization of GLUT5 induction in neonatal rat intestine. GR antagonist RU486 dose-dependently blocked dexamethasone effects on GLUT5 and arginase2. GR nuclear translocation occurred only when dexamethasone-injected pups were perfused with fructose, accompanied by increased GLUT5 abundance. Actinomycin D prevented dexamethasone-induced synthesis of an intermediate required for fructose-induced GLUT5 regulation. Receptor antagonist/agonist pharmacology in vivo, GR nuclear translocation assay, actinomycin D treatment, immunoblot The Journal of physiology Medium 18556366
2008 Fructose transporter Glut5 (Slc2a5) is essential for fructose-induced hypertension. Knockout of Slc2a5 in mice reduces jejunal fructose absorption and prevents fructose-induced increases in intestinal NaCl/water absorption and hypertension. Dietary fructose enhances expression of Slc2a5 and the chloride transporter Slc26a6 in mouse small intestine. Slc26a6 knockout mice, blood pressure measurement, dietary fructose feeding, immunoblot/expression analysis Kidney international Medium 18496516
2009 Luminal leptin activates PKCβII and AMPKα signaling, leading to insertion of GLUT5 (and GLUT2) into the brush-border membrane and enhanced fructose transport. In vivo, oral fructose triggers rapid gastric leptin release, which in turn upregulates GLUT5-mediated fructose transport via this regulatory loop. In vitro and in vivo isolated rat/mouse jejunal loops, leptin receptor signaling inhibitors, AMPK knockout mice, sugar transport assays, immunoblot PloS one Medium 19956534
2011 Fructose-induced expression of GLUT5 during intestinal development is epigenetically regulated: fructose perfusion and age both increase Pol II binding and histone H3 acetylation at the Glut5 promoter. Glucocorticoid receptor (GR) translocates to the nucleus and binds the Glut5 promoter in an age- and fructose-dependent manner, while GR binding to the Sglt1 promoter was not observed. Chromatin immunoprecipitation (ChIP) for Pol II, GR, and histone acetylation marks; intestinal perfusion in 10- and 20-day-old rats; RT-PCR The Biochemical journal High 21222652
2015 Crystal structures of rat GLUT5 (open outward-facing) and bovine GLUT5 (open inward-facing) reveal a major facilitator superfamily fold. Comparison of inward-facing structures of GLUT5 and human GLUT1 shows a single point mutation suffices to switch substrate-binding preference from fructose to glucose. Transport mechanism involves global rocker-switch re-orientation plus local asymmetric rearrangements of C-terminal TM7 and TM10 helices ('gated-pore' mechanism). X-ray crystallography (crystal structures in two conformations), point mutation functional analysis Nature High 26416735
2015 Fructose-induced increases in intestinal fructolytic and gluconeogenic enzyme expression specifically require GLUT5 (for fructose uptake) and KHK (for intracellular fructose metabolism), as demonstrated in GLUT5-KO, KHK-KO, and Rab11a-KO mice. Blocking GLUT5 trafficking to the apical membrane (via Rab11a-KO) also impairs fructose-induced enzyme upregulation, placing GLUT5 upstream of KHK in a feed-forward fructose-sensing pathway. GLUT5 knockout, KHK knockout, intestinal epithelial cell-specific Rab11a knockout mice; dietary fructose gavage; intestinal mRNA and protein expression American journal of physiology. Regulatory, integrative and comparative physiology High 26084694
2015 Rubusoside and astragalin-6-glucoside inhibit human GLUT5 fructose transport. A key residue distinguishing GLUT1 (Trp388) from GLUT5 (Ala396) determines ligand specificity: GLUT1-W388A became susceptible to astragalin-6-glucoside; GLUT5-A396W gained glucose transport activity and maintained inhibitor sensitivity, demonstrating this position controls substrate selectivity. Transport activity assays in Xenopus oocytes expressing individual GLUTs, site-directed mutagenesis, in silico docking Scientific reports High 26306809
2016 MSNBA (N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine) is a specific inhibitor of human GLUT5 fructose transport in proteoliposomes and in MCF7 cells (competitive inhibition, KI = 3.2 μM). MSNBA does not inhibit GLUT2, GLUT1, GLUT3, GLUT4, or bacterial GlcPSe. Mutagenesis studies implicate H387 of GLUT5 in inhibitor binding near the active site. Virtual screening, proteoliposome transport assay, MCF7 cell fructose uptake, site-directed mutagenesis, ligand docking Scientific reports High 27074918
2017 Fructose transport by GLUT5 shows stringent stereochemical requirement: inversion of a single stereocenter at C-3, C-4, or C-5 of fructose abolishes GLUT5-mediated transport (shifting uptake to GLUT1). 6-NBDF (all D-fructose configuration) is taken up via GLUT5; C-3, C-4, C-5 epimers are not. In silico docking with the GLUT5 crystal structure confirms stereochemical dependence. Fluorescent hexose uptake assays in breast cancer cell lines, Xenopus oocyte expression, in silico docking with GLUT5 crystal structure ACS chemical biology Medium 28205432
2017 Specific amino acid residues in GLUT5 required for fructose transport were identified using GLUT5/GLUT7 chimeras: critical positions reside in the first extracellular loop, TM5, TM7, TM8, TM9, TM10, and inter-TM loops 9-10 and 10-11. The Q167E substitution (analogous to rat Q166E) does not convert human GLUT5 into a glucose transporter but alters intracellular loop dynamics connecting TM6-7. Chimeric GLUT5/GLUT7 protein expression in NIH-3T3 cells, fructose radiotracer flux, fragment replacement analysis, molecular dynamics simulation The Journal of biological chemistry High 29259131
2019 LXRα (NR1H3) is a transcriptional regulator of GLUT5 expression. A functional LXR response element (LXRE) was identified at -385 bp relative to the GLUT5 transcriptional start site by promoter truncation and site-directed mutagenesis. LXR agonist T0901317 increases Glut5 mRNA and protein in mouse duodenum and adipose tissue in vivo. Unbiased GLUT5 promoter screen, promoter truncation reporter assay, site-directed mutagenesis of LXRE, LXR agonist treatment in mice, qPCR, Western blot Scientific reports High 31243309
2020 AKT1 and AKT3 activation in drug-resistant colon cancer cells causes aberrant downregulation of miR-125b-5p, leading to increased GLUT5 expression. Restoring miR-125b-5p blocked GLUT5-dependent fructose metabolism. GLUT5 silencing with siRNA attenuated mesenchymal marker expression and migratory activity in chemoresistant cells. AKT1/3 inhibition, miR-125b-5p mimic transfection, siRNA knockdown of GLUT5, migration/invasion assays, metabolite measurement Carcinogenesis Medium 32649737
2021 GLUT5 is sufficient to enable fructose-mediated cell proliferation across multiple cell types. GLUT5 overexpression in non-fructolytic cells enables growth in fructose medium; this fructose utilization occurs through glycolysis via hexokinase (HK), not ketohexokinase (KHK). Thus fructose uptake by GLUT5 is the limiting step for fructose-dependent proliferation. CRISPR-Cas9 KHK knockout, lentiviral GLUT5 overexpression in multiple cell lines, live cell imaging, Seahorse metabolic flux, LC/MS metabolomics, Crystal Violet assays Cancer & metabolism High 33762003
2021 S100P promotes SLC2A5/GLUT5 expression in colorectal cancer by binding to a specific region of the SLC2A5 promoter, reducing its methylation levels, and activating transcription. This mechanism promotes CRC cell invasion and metastasis both in vitro and in vivo. Methylation mass spectrometry sequencing, methylation-specific PCR, bisulfite sequencing PCR, ChIP-qPCR, luciferase reporter assay, intrasplenic inoculation mouse model British journal of cancer Medium 34188196
2021 GLUT5 deficiency reduces GLUT5-knockout mouse colitis severity upon fructose feeding compared to overexpression, mediated by changes in colonic microbiota (reversed by antibiotics). GLUT5 controls colonic fructose levels that shape gut microbiota composition and thereby modulate colitis severity. Glut5 knockout and overexpressor transgenic mice, DSS colitis model, dietary fructose feeding, fecal microbiota analysis, broad-spectrum antibiotics treatment American journal of physiology. Gastrointestinal and liver physiology Medium 34133236
2022 IL-6 activates fructose uptake and fructolysis in cancer cells via STAT3-mediated transcriptional activation of GLUT5. STAT3 associates with the GLUT5 promoter region in response to IL-6. Knockdown of GLUT5 abolishes IL-6-induced fructose uptake and compromises IL-6-elicited tumor cell proliferation. IL-6 treatment, STAT3 ChIP, GLUT5 promoter binding assay, GLUT5 knockdown, fructose uptake assay, cell proliferation assay International journal of biological sciences Medium 35813468
2022 GLUT5-mediated fructose utilization promotes lung cancer cell migration by upregulating AKT phosphorylation via a glycolysis/lactate/AKT pathway. SLC2A5 deletion blocked migration and AKT activation; glycolysis inhibitor 2-DG and GLUT5-specific inhibitor 2,5-AM suppressed migration and AKT activation. In vivo tail-vein metastasis experiments confirmed reduced metastatic potential upon SLC2A5 deletion. CRISPR/Cas9 SLC2A5 deletion, retrovirus SLC2A5 overexpression, Transwell migration assay, Western blot for AKT phosphorylation, lactate assay, 2-DG and 2,5-AM inhibitor experiments, tail-vein metastasis mouse model Clinical & translational oncology Medium 36454516
2022 CRISPR/Cas9-mediated inactivation of SLC2A5 inhibits cancer cell migration and metastasis in vivo. SLC2A5-attenuated cells show dramatic alterations in mitochondrial architecture and localization, revealing a role for GLUT5 in directing mitochondrial function for cancer cell motility. CRISPR/Cas9 gene inactivation, in vitro migration assays, multiple in vivo animal metastasis models, mitochondrial imaging Frontiers in cell and developmental biology Medium 36268513
2023 Molecular dynamics simulations show GLUT5 spontaneously transitions through an occluded state resembling PfHT1, with TM7b gating helix rearrangements. D-fructose coordination lowers the energetic barriers between outward- and inward-facing states. The binding mode is consistent with biochemical analysis, and GLUT5 uses allosteric coupling of sugar binding with extracellular gate closure (via TM7b) to achieve substrate selectivity, rather than achieving high affinity through substrate-binding site alone. Enhanced sampling molecular dynamics simulations, biochemical fructose transport analysis eLife Medium 37405832
2007 GLUT5 physically interacts with prestin in cochlear outer hair cells. Using FRET (by FACS, acceptor photobleaching, and FLIM) and co-immunoprecipitation in HEK293T cells, both homomeric prestin-prestin and heteromeric prestin-GLUT5 interactions were demonstrated. Co-immunoprecipitation, confocal colocalization, FRET-FACS, FRET-acceptor photobleaching, FRET-FLIM in HEK293T cells Developmental neurobiology Medium 17443803
1998 GLUT5 domains responsible for fructose transport were further mapped using GLUT5/GLUT3 chimeras: the GLUT5 N-terminus through TM3 and the segment between TM5 and TM11 are both necessary for fructose uptake. Chimeras lacking either region failed to transport fructose despite surface expression confirmed by biotin exofacial labeling. Chimeric GLUT5/GLUT3 protein expression in Xenopus oocytes, radiolabeled sugar uptake, exofacial biotin labeling Endocrinology Medium 9492009
2018 d-Allulose is a substrate of GLUT5. Plasma d-allulose absorption was enhanced in fructose-pre-fed rats (with higher GLUT5 expression), and co-gavage with fructose competitively dampened d-allulose absorption. Radiotracer assay showed d-allulose inhibited D-[14C]-fructose uptake (54.8% at 50 mM), but with lower affinity than fructose itself (16.4% inhibition at 50 mM). Dietary prefeeding to modulate GLUT5, plasma allulose measurement, competitive radiotracer D-[14C]-fructose uptake assay Food chemistry Medium 30502192
2023 SNAI1 and SNAI2 transcription factors repress SLC2A5/GLUT5 expression. Trichostatin A (HDAC inhibitor) induces SNAI1/SNAI2 expression, which in turn suppresses SLC2A5 transcription and sensitizes colon cancer cells to cisplatin and oxaliplatin. SNAI1/SNAI2 overexpression, trichostatin A treatment, RT-PCR, Western blot, cell viability assays European journal of pharmacology Medium 37062501

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 Fructose transporter in human spermatozoa and small intestine is GLUT5. The Journal of biological chemistry 413 1634504
2008 Regulation of the fructose transporter GLUT5 in health and disease. American journal of physiology. Endocrinology and metabolism 339 18398011
1990 Human facilitative glucose transporters. Isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusual glucose transporter pseudogene-like sequence (GLUT6). The Journal of biological chemistry 328 1695905
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