{"uniprot":"Q6PXP3","gene":"SLC2A7","name":"Solute carrier family 2, facilitated glucose transporter member 7","organism":"Homo sapiens (Human)","status":"dark","length":512,"sequence":"MENKEAGTPPPIPSREGRLQPTLLLATLSAAFGSAFQYGYNLSVVNTPHKVFKSFYNETYFERHATFMDGKLMLLLWSCTVSMFPLGGLLGSLLVGLLVDSCGRKGTLLINNIFAIIPAILMGVSKVAKAFELIVFSRVVLGVCAGISYSALPMYLGELAPKNLRGMVGTMTEVFVIVGVFLAQIFSLQAILGNPAGWPVLLALTGVPALLQLLTLPFFPESPRYSLIQKGDEATARQALRRLRGHTDMEAELEDMRAEARAERAEGHLSVLHLCALRSLRWQLLSIIVLMAGQQLSGINAINYYADTIYTSAGVEAAHSQYVTVGSGVVNIVMTITSAVLVERLGRRHLLLAGYGICGSACLVLTVVLLFQNRVPELSYLGIICVFAYIAGHSIGPSPVPSVVRTEIFLQSSRRAAFMVDGAVHWLTNFIIGFLFPSIQEAIGAYSFIIFAGICLLTAIYIYVVIPETKGKTFVEINRIFAKRNRVKLPEEKEETIDAGPPTASPAKETSF","function_summary":"A multi-pass membrane carrier that forms a 12-helix pore to mediate energy-independent, facilitated diffusion of hexoses across the cell surface. It preferentially conducts glucose and fructose by an alternating-access mechanism that binds and releases sugars without coupling to ion gradients, thereby supplying intracellular metabolism and maintaining extracellular–cytosolic sugar balance at the plasma membrane.","plain_language":"SLC2A7 has barely been studied. The model's best guess: A multi-pass membrane carrier that forms a 12-helix pore to mediate energy-independent, facilitated diffusion of hexoses across the cell surface. It preferentially conducts glucose and fructose by an alternating-access mechanism that binds and releases sugars without coupling to ion gradients, thereby supplying intracellular metabolism and maintaining extracellular–cytosolic sugar balance at the plasma membrane.","uniprot_summary":"Probable glucose transporter.","go_terms":{"molecular_function":[{"id":"GO:0015145","label":"monosaccharide transmembrane transporter activity"},{"id":"GO:0005353","label":"fructose transmembrane transporter activity"},{"id":"GO:0055056","label":"D-glucose transmembrane transporter activity"}],"biological_process":[{"id":"GO:0008645","label":"hexose transmembrane transport"},{"id":"GO:1904659","label":"glucose transmembrane transport"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR036259","name":"MFS transporter superfamily","type":"homologous_superfamily","start":15,"end":485},{"id":"IPR020846","name":"Major facilitator superfamily domain","type":"domain","start":27,"end":470},{"id":"IPR045263","name":"Glucose transporter GLUT","type":"family","start":18,"end":486},{"id":"IPR005828","name":"Major facilitator, sugar transporter-like","type":"family","start":27,"end":481},{"id":"IPR003663","name":"Sugar/inositol transporter","type":"family","start":35,"end":45},{"id":"IPR003663","name":"Sugar/inositol transporter","type":"family","start":49,"end":477},{"id":"IPR005829","name":"Sugar transporter, conserved site","type":"conserved_site","start":140,"end":165},{"id":"IPR005829","name":"Sugar transporter, conserved site","type":"conserved_site","start":338,"end":354}],"reasoning":"I begin with the InterPro architecture. The polypeptide is dominated by IPR036259 (MFS transporter superfamily, residues 15–485) and IPR020846 (Major facilitator superfamily domain, residues 27–470), establishing a canonical major facilitator superfamily fold that forms a 12-helix alternating-access pore across the membrane. Within this scaffold, IPR045263 (Glucose transporter GLUT family, residues 18–486) and IPR005828 (Major facilitator, sugar transporter-like family, residues 27–481) specify substrate class and physiological role as a hexose transporter akin to vertebrate GLUTs. Two conserved sequence signatures, IPR005829 (Sugar transporter, conserved site, residues 140–165) and IPR005829 (Sugar transporter, conserved site, residues 338–354), map to core helices that stabilize the inward- and outward-facing states and coordinate sugar binding/release. The presence of IPR003663 (Sugar/inositol transporter family, residues 35–45 and 49–477) reinforces a sugar-preferring cavity and supports broad monosaccharide recognition. The ordered layout—MFS superfamily core flanked by GLUT-family determinants and paired conserved sites—causes an energy-independent, alternating-access mechanism that mediates facilitated diffusion of hexoses.\n\nThis architecture dictates molecular function. The GLUT-family determinants and sugar-transporter signatures confer monosaccharide transmembrane transporter activity, matching GO:0015145 monosaccharide transmembrane transporter activity. Substrate preference and conserved-site chemistry align with high-capacity flux of glucose and fructose, supporting GO:0055056 D-glucose transmembrane transporter activity and GO:0005353 fructose transmembrane transporter activity. The absence of proton-binding motifs and the MFS context that supports uniport rather than symport point to facilitative, gradient-driven transport rather than secondary active uptake.\n\nFrom function to process, a facilitative hexose pore directly executes GO:1904659 glucose transmembrane transport and GO:0008645 hexose transmembrane transport. By equilibrating extracellular and cytosolic sugar pools, the transporter feeds glycolysis and biosynthetic pathways without direct ATP coupling.\n\nCellular location follows from the fold and role. A 12-helix MFS core requires a lipid bilayer, and GLUT-family members operate at the cell surface to exchange sugars with the extracellular milieu. This places the protein at the GO:0005886 plasma membrane and agrees with a multi-pass membrane topology.\n\nMechanistically, the transporter cycles between outward- and inward-facing states to bind and release glucose and fructose through a central cavity shaped by the GLUT-family core and the two conserved sites (140–165 and 338–354). I hypothesize that trafficking and regulation occur via endocytic and scaffolding pathways: association with caveolin-1 could cluster the transporter in membrane microdomains; PDZ-domain adaptors such as SLC9A3R1 (NHERF1) may tether it to cortical actin; and clathrin adaptor complexes (e.g., AP-2) likely mediate internalization. Functional coupling to metabolic enzymes and cytosolic adaptors would tune flux, but the primary action remains high-capacity, energy-independent hexose exchange at the plasma membrane.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6PXP3.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6PXP3"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6PXP3/entry","atlas":"/p/Q6PXP3"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}