{"uniprot":"Q96FV3","gene":"TSPAN17","name":"Tetraspanin-17","organism":"Homo sapiens (Human)","status":"dark","length":270,"sequence":"MPGKHQHFQEPEVGCCGKYFLFGFNIVFWVLGALFLAIGLWAWGEKGVLSNISALTDLGGLDPVWLFVVVGGVMSVLGFAGCIGALRENTFLLKFFSVFLGLIFFLELATGILAFVFKDWIRDQLNLFINNNVKAYRDDIDLQNLIDFAQEYWSCCGARGPNDWNLNIYFNCTDLNPSRERCGVPFSCCVRDPAEDVLNTQCGYDVRLKLELEQQGFIHTKGCVGQFEKWLQDNLIVVAGVFMGIALLQIFGICLAQNLVSDIKAVKANW","function_summary":"A four-pass membrane organizer that assembles tetraspanin-enriched microdomains to cluster membrane enzymes and adhesion receptors. It is synthesized and folded within the endoplasmic reticulum lumen and delivered to the plasma membrane, where it scaffolds and stabilizes receptor–enzyme assemblies that govern adhesion and signaling. By concentrating and positioning catalytic partners and their associated complexes, it promotes their proper trafficking and retention within membrane territories.","plain_language":"TSPAN17 has barely been studied. The model's best guess: A four-pass membrane organizer that assembles tetraspanin-enriched microdomains to cluster membrane enzymes and adhesion receptors. It is synthesized and folded within the endoplasmic reticulum lumen and delivered to the plasma membrane, where it scaffolds and stabilizes receptor–enzyme assemblies that govern adhesion and signaling.","uniprot_summary":"May be involved in adhesion processes.","go_terms":{"molecular_function":[{"id":"GO:0019899","label":"enzyme binding"}],"biological_process":[{"id":"GO:0072594","label":"establishment of protein localization to organelle"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"},{"id":"GO:0005788","label":"endoplasmic reticulum lumen"}]},"interpro":[{"id":"IPR008952","name":"Tetraspanin, EC2 domain superfamily","type":"homologous_superfamily","start":115,"end":235},{"id":"IPR000301","name":"Tetraspanin, animals","type":"family","start":16,"end":265},{"id":"IPR018499","name":"Tetraspanin/Peripherin","type":"family","start":18,"end":260},{"id":"IPR018503","name":"Tetraspanin, conserved site","type":"conserved_site","start":71,"end":93}],"reasoning":"I begin with the InterPro architecture. The sequence carries IPR000301 (Tetraspanin, animals family) from residues 16–265 and IPR018499 (Tetraspanin/Peripherin family) from residues 18–260, establishing a canonical four-pass tetraspanin scaffold with short cytosolic N- and C-termini and two extracellular loops. Within this framework, IPR008952 (Tetraspanin, EC2 domain superfamily) spans residues 115–235, marking the large extracellular loop (EC2) that typically contains the CCG motif and mediates high-affinity lateral interactions and adhesion-receptor clustering. IPR018503 (Tetraspanin, conserved site) at residues 71–93 denotes the hallmark cysteine-rich signature that stabilizes EC2 through disulfide bonding and governs partner selectivity. The ordered layout—four transmembrane helices bracketing a structured EC2—causes the protein to assemble and stabilize membrane microdomains that concentrate specific enzymes and receptors.\n\nThis tetraspanin architecture dictates molecular function as enzyme binding (GO:0019899). The EC2 platform and conserved tetraspanin core create a multivalent binding surface that recruits and organizes membrane-associated enzymes and their adaptors. Such enzyme-tethering behavior is a defining property of tetraspanin-enriched microdomains and explains selective capture of catalytic partners at the cell surface.\n\nFrom this binding activity, the biological process follows: establishment of protein localization to organelle (GO:0072594). By forming lateral assemblies, the tetraspanin scaffold directs the trafficking and retention of its partners within membrane territories that communicate with endosomal and secretory organelles. This organizational role steers client proteins toward appropriate membrane compartments and extracellular interfaces, aligning with a function in positioning adhesion and signaling modules.\n\nCellular location is inferred from both topology and biosynthetic route. The four-pass membrane core and extracellular loop composition specify a membrane-resident protein that matures in the secretory pathway. Its assembly and disulfide-bonded EC2 loop necessitate folding and quality control within the endoplasmic reticulum lumen (GO:0005788), followed by delivery to the plasma membrane (GO:0005886). The experimentally supported annotation of a multi-pass membrane protein is consistent with this itinerary and with stable residence at the cell surface.\n\nMechanistically, the protein likely nucleates tetraspanin-enriched microdomains that cluster adhesion receptors and membrane enzymes. By binding and corralling enzymes and their receptor partners, it stabilizes adhesion complexes and modulates signaling thresholds at the cell surface. I hypothesize that it transiently associates with integrins and metalloprotease assemblies during biosynthesis in the ER lumen and then at the plasma membrane, where it orchestrates the spatial organization and trafficking of its client proteins and pathways.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96FV3.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96FV3"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96FV3/entry","atlas":"/p/Q96FV3"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}