{"uniprot":"A6NKX4","gene":"SLC22A31","name":"Putative solute carrier family 22 member 31","organism":"Homo sapiens (Human)","status":"dark","length":556,"sequence":"MEQEARVLRAAGGFGRARRLLASASWVPCIVLGLVLSSEELLTAQPAPHCRPDPTLLPPALRALRGPALLDAAIPRLGPTRAPAEALGVLSPSYLAPLTRAPRPSSWASCSGAAAGPTWNLVCGDGWKVPLEQVSHLLGWLLGCVILGAGCDRFGRRAVFVASLVLTTGLGASEALAASFPTLLVLRLLHGGTLAGALLALYLARLELCDPPHRLAFSMGAGLFSVVGTLLLPGLAALVQDWRLLQGLGALMSGLLLLFWGFPALFPESPCWLLATGQVARARKILWRFAEASGVGPGDSSLEENSLATELTMLSARSPQPRYHSPLGLLRTRVTWRNGLILGFSSLVGGGIRASFRRSLAPQVPTFYLPYFLEAGLEAAALVFLLLTADCCGRRPVLLLGTMVTGLASLLLLAGAQYLPGWTVLFLSVLGLLASRAVSALSSLFAAEVFPTVIRGAGLGLVLGAGFLGQAAGPLDTLHGRQGFFLQQVVFASLAVLALLCVLLLPESRSRGLPQSLQDADRLRRSPLLRGRPRQDHLPLLPPSNSYWAGHTPEQH","function_summary":"A human multi-pass membrane carrier that belongs to the major facilitator superfamily and operates by an alternating-access mechanism to move small solutes across lipid bilayers. Its architecture and binding capacity indicate a secondary-active transporter that contributes to cellular iron handling by mediating siderophore- and iron-related flux, likely coupled to proton gradients. The protein is incorporated into vesicular pathways and can be packaged into extracellular vesicles, positioning it at membrane–vesicle interfaces where it coordinates iron transport with trafficking and exosome biogenesis.","plain_language":"SLC22A31 has barely been studied. The model's best guess: A human multi-pass membrane carrier that belongs to the major facilitator superfamily and operates by an alternating-access mechanism to move small solutes across lipid bilayers. Its architecture and binding capacity indicate a secondary-active transporter that contributes to cellular iron handling by mediating siderophore- and iron-related flux, likely coupled to proton gradients.","uniprot_summary":"Putative transporter.","go_terms":{"molecular_function":[{"id":"GO:0022857","label":"transmembrane transporter activity"},{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006826","label":"iron ion transport"},{"id":"GO:0015891","label":"siderophore transport"}],"cellular_component":[{"id":"GO:0070062","label":"extracellular exosome"}]},"interpro":[{"id":"IPR036259","name":"MFS transporter superfamily","type":"homologous_superfamily","start":110,"end":517},{"id":"IPR020846","name":"Major facilitator superfamily domain","type":"domain","start":81,"end":510},{"id":"IPR005828","name":"Major facilitator, sugar transporter-like","type":"family","start":137,"end":317}],"reasoning":"I begin with the InterPro architecture. The core of the protein is defined by IPR020846 (Major facilitator superfamily domain, residues 81–510) and reinforced by IPR036259 (MFS transporter superfamily, homologous superfamily, residues 110–517), together indicating a classical MFS fold that forms a 12-transmembrane helical bundle operating by alternating-access transport. Embedded within this scaffold is IPR005828 (Major facilitator, sugar transporter-like family, residues 137–317), which specifies a sugar-transporter-like lineage within MFS. This ordered layout—an extended MFS core with a central sugar-transporter-like module—causes secondary-active transmembrane transport driven by proton or ion gradients rather than ATP hydrolysis. Such an architecture directly supports GO:0022857 transmembrane transporter activity as the molecular function and also accommodates GO:0005515 protein binding, because many MFS carriers use cytosolic loops and termini as docking sites for regulatory and trafficking partners that tune transport cycles.\n\nFrom this transporter foundation, I infer the biological role by considering substrate class and physiological context. MFS carriers frequently move small solutes, including metal–chelate complexes. The presence of GO:0015891 siderophore transport and GO:0006826 iron ion transport points to a specialization: the transporter likely handles ferric iron either directly or via siderophore-like chelation at the membrane interface. The sugar-transporter-like signature within MFS often supports proton-coupled uptake; applying that mechanism to iron chemistry yields a plausible route: proton-motive-force–coupled translocation of iron or iron–chelate assemblies across endolysosomal or plasma membranes, thereby contributing to cellular iron economy.\n\nCellular placement follows from both the multi-pass architecture and vesicular association. The MFS fold dictates a membrane-embedded carrier, consistent with a multi-pass membrane protein. Its detection in extracellular vesicle pathways aligns with GO:0070062 extracellular exosome, suggesting that the transporter is incorporated into intraluminal vesicles and subsequently released. Such packaging routes are typical for membrane transporters that undergo endocytic recycling and sorting.\n\nMechanistically, I propose that the transporter cycles between outward- and inward-facing states to move iron-containing substrates across lipid bilayers. Protein-binding capacity (GO:0005515) would enable assembly with endocytic adaptors and iron-handling factors, coordinating siderophore/iron flux with vesicular trafficking. Likely interaction partners include clathrin-mediated endocytic machinery and iron-trafficking modules that localize and regulate the transporter at membrane–vesicle interfaces, consistent with its exosome association and role in iron and siderophore transport.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A6NKX4.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A6NKX4"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A6NKX4/entry","atlas":"/p/A6NKX4"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}