{"uniprot":"Q5TF58","gene":"IFFO2","name":"Intermediate filament family orphan 2","organism":"Homo sapiens (Human)","status":"dark","length":517,"sequence":"MVNSLLFGEMALAFGCPPGGGGGGCPGGGGGGGGAGPGPSPVTAALRDDLGSNIHLLKGLNVRFRCFLAKVHELERRNRLLEKQLEQQQSERERRLRYKTFSREQAVQTGPELLRPPAPGGGHGLSSGAAAGANANAVALGGLPPGGGSHPQHYGRLPGTIWSYTQVRRTGGGGVETVQGPGVSWVHPDGVGVQIDTITPEIRALYNVLAKVKRERDEYKRRWEEELAKRMNLQTMVDTLQEAAQEADAIQEEMNEKIERLKAELVVFKGLMSDPMTDLDTKIQEKAMKVDMDICRRIDITAKLCDVAQQRNSEDVSKIFQVVPKKKERKVASDDDISEQDGEVNRFSDDEVGSMNITDEMKRMFNQLRETFDFDDDCDSLTWEENEDTLLLWEDFTNCNPTIDLQGEQEENLGNLIHETESFFKTRDKEYQETIGQIELELATAKSDMNRHLHEYMEMCSMKRGLDVQMETCRRLIKGSADRNSPSPSSVASSDSGSTDEIQDEFEREADVEPMVS","function_summary":"A nuclear intermediate-filament scaffold that assembles and stabilizes large protein complexes through an extended coiled-coil core. By organizing nuclear assemblies, it modulates RNA metabolism and tunes signaling pathways by sequestering and presenting client proteins. This filamentous matrix supports both stabilization and ubiquitin-mediated turnover of nuclear substrates, enhances canonical Wnt pathway output, and coordinates nuclear–cytoplasmic exchange through regulated export, collectively shaping kinase activity and proteostasis within the nucleoplasm.","plain_language":"IFFO2 has barely been studied. The model's best guess: A nuclear intermediate-filament scaffold that assembles and stabilizes large protein complexes through an extended coiled-coil core. By organizing nuclear assemblies, it modulates RNA metabolism and tunes signaling pathways by sequestering and presenting client proteins.","uniprot_summary":"May be involved in RNA metabolism or signal transduction.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0051649","label":"establishment of localization in cell"},{"id":"GO:0042177","label":"negative regulation of protein catabolic process"},{"id":"GO:0030177","label":"positive regulation of Wnt signaling pathway"},{"id":"GO:0043393","label":"regulation of protein binding"},{"id":"GO:0050821","label":"protein stabilization"},{"id":"GO:0000079","label":"regulation of cyclin-dependent protein serine/threonine kinase activity"},{"id":"GO:0016070","label":"RNA metabolic process"},{"id":"GO:0006611","label":"protein export from nucleus"},{"id":"GO:0090263","label":"positive regulation of canonical Wnt signaling pathway"},{"id":"GO:0033674","label":"positive regulation of kinase activity"},{"id":"GO:0045862","label":"positive regulation of proteasomal protein catabolic process"},{"id":"GO:0006469","label":"negative regulation of protein kinase activity"},{"id":"GO:0032436","label":"positive regulation of proteasomal ubiquitin-dependent protein catabolic process"},{"id":"GO:0031398","label":"positive regulation of protein ubiquitination"}],"cellular_component":[{"id":"GO:0005654","label":"nucleoplasm"}]},"interpro":[{"id":"IPR039008","name":"Intermediate filament, rod domain","type":"domain","start":52,"end":484}],"reasoning":"I begin with the InterPro architecture: a single long coiled-coil module, IPR039008 (Intermediate filament, rod domain) spanning residues 52–484. This canonical intermediate-filament rod domain dictates obligate parallel coiled-coil dimerization and higher-order filament assembly. In nuclear intermediate-filament class proteins, this rod-centered architecture causes extensive homotypic and heterotypic protein binding through filament formation and adaptor docking, establishing a scaffold that concentrates regulatory complexes rather than catalyzing chemistry. This structural logic directly supports GO:0005515 protein binding as the primary molecular function.\n\nFrom this filament scaffold, several process-level consequences follow. First, the filamentous core stabilizes and organizes nuclear assemblies that govern RNA metabolism and chromatin-associated pathways, aligning with GO:0016070 RNA metabolic process. The same scaffold can buffer client proteins from degradation by sequestering them and recruiting stabilizing partners, which explains GO:0050821 protein stabilization and GO:0043393 regulation of protein binding. By forming a high-avidity hub, the rod domain increases local concentration of signaling and cell-cycle regulators, enabling both GO:0033674 positive regulation of kinase activity and GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity; conversely, selective sequestration and competition at the scaffold can dampen kinase output, accounting for GO:0006469 negative regulation of protein kinase activity.\n\nThe scaffold’s influence on proteostasis emerges from its dual role in assembly and turnover. Filament-associated complexes can both shield substrates from degradation (GO:0042177 negative regulation of protein catabolic process) and promote ubiquitin-dependent turnover when assembly cues favor that route (GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process; GO:0031398 positive regulation of protein ubiquitination). This bidirectional control is a natural outcome of a filamentous hub that toggles between assembly and handoff to ubiquitin machinery.\n\nCellular signaling pathways tied to the scaffold are particularly evident in canonical Wnt signaling. By stabilizing nuclear pools of pathway components and facilitating their export, the filament architecture can enhance pathway throughput, consistent with GO:0090263 positive regulation of canonical Wnt signaling pathway and GO:0006611 protein export from nucleus. The absence of transmembrane segments and the presence of a nuclear intermediate-filament rod domain point to a soluble nuclear structural matrix rather than a membrane compartment, situating the protein in the GO:0005654 nucleoplasm.\n\nIntegrating these features yields a mechanistic model: a nuclear intermediate-filament scaffold that nucleates large assemblies via its rod domain, thereby tuning RNA processing and signaling by modulating partner binding, sequestration, and handoff to ubiquitin pathways. This architecture predicts interactions with nuclear lamina and chromatin-associated complexes, and it rationalizes roles in both stabilizing and turnover-prone nuclear clients.\n\nFrom this model, I hypothesize interaction partners that fit the scaffold’s nuclear role: lamina constituents (LMNA/LMNB1) and other class VI/IV intermediate-filament proteins (PRMT1-associated nuclear IFs) that co-assemble on the filament core; chromatin and RNA-processing assemblies that dock to coiled-coil hubs; and transport/export factors that couple nuclear assemblies to cytoplasmic pathways. These partners would collectively explain the observed coupling to kinase regulation, Wnt pathway potentiation, and regulated protein export from the nucleus.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q5TF58.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q5TF58"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q5TF58/entry","atlas":"/p/Q5TF58"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}