{"uniprot":"Q8IXY8","gene":"PPIL6","name":"Probable inactive peptidyl-prolyl cis-trans isomerase-like 6","organism":"Homo sapiens (Human)","status":"dark","length":311,"sequence":"MARPQPCGPPHARCGSPSLPERPLQVKVVGLFSCPNFQIAKSAAENLKNNHPSKFEDPILVPLQEFAWHQYLQEKKRELKNETWEYSSSVISFVNGQFLGDALDLQKWAHEVWDIVDIKPSALYDALTEDFSAKFLRDTKHDFVFLDICIDSSPIGRLIFELYCDVCPKTCKNFQVLCTGKAGFSQRGIRLHYKNSIFHRIVQNGWIQGGDIVYGKGDNGESIYGPTFEDENFSVPHNKRGVLGMANKGRHSNGSQFYITLQATPYLDRKFVAFGQLIEGTEVLKQLELVPTQNERPIHMCRITDSGDPYA","function_summary":"A soluble human cyclophilin-fold protein that operates as a binding-centric adaptor in proteostasis. Its cyclophilin core mediates multivalent protein interactions that remodel client conformations and steer them toward ubiquitin-dependent degradation. It functions predominantly in the cytoplasm, with additional activity in the nucleus and incorporation into extracellular vesicles, where it likely assists in client handling and cargo selection through transient assemblies that couple folding/remodeling to selective turnover.","plain_language":"PPIL6 has barely been studied. The model's best guess: A soluble human cyclophilin-fold protein that operates as a binding-centric adaptor in proteostasis. Its cyclophilin core mediates multivalent protein interactions that remodel client conformations and steer them toward ubiquitin-dependent degradation.","uniprot_summary":"Probable cyclophilin.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006511","label":"ubiquitin-dependent protein catabolic process"}],"cellular_component":[{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0070062","label":"extracellular exosome"},{"id":"GO:0005634","label":"nucleus"}]},"interpro":[{"id":"IPR029000","name":"Cyclophilin-like domain superfamily","type":"homologous_superfamily","start":131,"end":310},{"id":"IPR002130","name":"Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain","type":"domain","start":145,"end":308}],"reasoning":"I begin with the InterPro architecture. The core of the protein is a cyclophilin module: IPR029000 (Cyclophilin-like domain superfamily, residues 131–310) encompasses and frames IPR002130 (Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain, residues 145–308). This arrangement—an internally defined cyclophilin catalytic fold embedded within the broader cyclophilin-like superfamily—establishes a classical cyclophilin scaffold. Cyclophilin folds create a solvent-exposed pocket that binds proline-containing peptide segments and frequently mediates chaperone-like interactions. In many cytoplasmic cyclophilins, this architecture drives protein–protein recognition and conformational editing, which causally supports a primary molecular function of protein binding (GO:0005515).\n\nFrom this binding-centric cyclophilin core, I infer how the protein influences cellular pathways. Cyclophilin folds often act as adaptors that couple folding/remodeling to selective degradation. The explicit linkage to ubiquitin-dependent protein catabolic process (GO:0006511) follows naturally: a cyclophilin scaffold can transiently isomerize or chaperone client proteins to expose or stabilize degron-bearing conformations, thereby facilitating their handoff to ubiquitin–proteasome pathways. The architecture thus provides the physical basis for assembling transient complexes that bias substrates toward ubiquitination and subsequent turnover.\n\nCellular localization follows from both the soluble cyclophilin fold and the observed compartmental distribution. The absence of transmembrane features and the soluble nature of cyclophilins place the protein in the cytoplasm (GO:0005737). Its presence in the nucleus (GO:0005634) is consistent with shuttling cyclophilin modules that regulate chromatin-associated or transcriptional clients. Detection in extracellular exosomes (GO:0070062) indicates that a fraction of the cytoplasmic pool is packaged into secreted vesicles; this is mechanistically compatible with cyclophilin-mediated client handling and vesicular sorting.\n\nIntegrating these layers yields a mechanistic hypothesis. The cyclophilin domain binds client proteins and assembly factors, stabilizing conformations that favor ubiquitin-dependent proteostasis. In the cytoplasm and nucleus, it likely forms transient complexes with E3 ligase adaptors and chaperones to triage substrates. Packaging into exosomes suggests an auxiliary role in extracellular vesicle cargo selection, potentially exporting bound client proteins or signaling modules. I therefore expect interactions with ubiquitin–proteasome pathway components and vesicle biogenesis machinery, with the cyclophilin fold serving as the modular interaction hub that tunes substrate fate across cytoplasmic, nuclear, and exosomal compartments.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8IXY8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8IXY8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8IXY8/entry","atlas":"/p/Q8IXY8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}