{"uniprot":"P08670","gene":"VIM","name":"Vimentin","organism":"Homo sapiens (Human)","status":"known control","length":466,"sequence":"MSTRSVSSSSYRRMFGGPGTASRPSSSRSYVTTSTRTYSLGSALRPSTSRSLYASSPGGVYATRSSAVRLRSSVPGVRLLQDSVDFSLADAINTEFKNTRTNEKVELQELNDRFANYIDKVRFLEQQNKILLAELEQLKGQGKSRLGDLYEEEMRELRRQVDQLTNDKARVEVERDNLAEDIMRLREKLQEEMLQREEAENTLQSFRQDVDNASLARLDLERKVESLQEEIAFLKKLHEEEIQELQAQIQEQHVQIDVDVSKPDLTAALRDVRQQYESVAAKNLQEAEEWYKSKFADLSEAANRNNDALRQAKQESTEYRRQVQSLTCEVDALKGTNESLERQMREMEENFAVEAANYQDTIGRLQDEIQNMKEEMARHLREYQDLLNVKMALDIEIATYRKLLEGEESRISLPLPNFSSLNLRETNLDSLPLVDTHSKRTLLIKTVETRDGQVINETSQHHDDLE","function_summary":"A cytoplasmic intermediate filament subunit that assembles into a filamentous cytoskeletal network, providing mechanical support and a multivalent scaffold that organizes other cytoskeletal and membrane-associated assemblies. Through its head–rod–tail architecture, it builds and regulates filament polymers that stabilize epithelial and mesenchymal architecture, coordinate RNA–protein assemblies that tune mRNA stability and translation, and couple cytoskeletal organization to pathways that enhance collagen production and cellular responses to inflammatory cues.","plain_language":"VIM is a well-known protein (structural / cytoskeleton). What biology already knows: Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. We use it to check whether the model gets it right.","uniprot_summary":"Vimentins are class-3 intermediate filaments (IF) that are part of the filament system which maintains cell integrity and which undergoes a dynamic reorganization depending on different cellular conditions.","go_terms":{"molecular_function":[{"id":"GO:0060090","label":"molecular adaptor activity"},{"id":"GO:0005200","label":"structural constituent of cytoskeleton"},{"id":"GO:0042802","label":"identical protein binding"},{"id":"GO:0097110","label":"scaffold protein binding"},{"id":"GO:0019904","label":"protein domain specific binding"},{"id":"GO:0003725","label":"double-stranded RNA binding"}],"biological_process":[{"id":"GO:0032967","label":"positive regulation of collagen biosynthetic process"},{"id":"GO:0043488","label":"regulation of mRNA stability"},{"id":"GO:0071222","label":"cellular response to lipopolysaccharide"},{"id":"GO:0045727","label":"positive regulation of translation"},{"id":"GO:0032495","label":"response to muramyl dipeptide"}],"cellular_component":[{"id":"GO:0045111","label":"intermediate filament cytoskeleton"}]},"interpro":[{"id":"IPR006821","name":"Intermediate filament head, DNA-binding domain","type":"domain","start":7,"end":101},{"id":"IPR039008","name":"Intermediate filament, rod domain","type":"domain","start":102,"end":411},{"id":"IPR050405","name":"Intermediate filament structural protein","type":"family","start":4,"end":454},{"id":"IPR018039","name":"Intermediate filament protein, conserved site","type":"conserved_site","start":397,"end":405}],"reasoning":"I begin with the InterPro architecture. The N-terminus carries IPR006821 (Intermediate filament head, DNA-binding domain, residues 7–101), followed by IPR039008 (Intermediate filament, rod domain, residues 102–411), and a C-terminal conserved motif IPR018039 (Intermediate filament protein, conserved site, residues 397–405). The entire polypeptide is encompassed by IPR050405 (Intermediate filament structural protein family, residues 4–454). This canonical intermediate filament (IF) layout—an intrinsically disordered head, a central coiled-coil rod, and a conserved tail—dictates assembly into higher-order cytoskeletal filaments. The head domain nucleates filament formation and regulates assembly through phosphorylation and nucleic acid contacts; the rod domain enforces parallel coiled-coil dimerization and lateral packing; and the conserved tail motif stabilizes end-to-end annealing and network integrity. This architecture causes structural constituent activity toward the cytoskeleton and creates multivalent interfaces for filament–filament and filament–complex associations.\n\nFrom this scaffold, I infer molecular functions. The rod-driven polymerization and head-mediated regulation directly produce GO:0005200 structural constituent of cytoskeleton. The filament network’s role as a hub that recruits and organizes other cytoskeletal and membrane-associated assemblies explains GO:0060090 molecular adaptor activity and GO:0097110 scaffold protein binding; the IF lattice provides both mechanical support and a docking platform for diverse partners. The propensity of IF proteins to form homo- and hetero-oligomers supports GO:0042802 identical protein binding. The presence of a DNA/RNA-contacting head and reports of nucleic acid association justify GO:0003725 double-stranded RNA binding, which aligns with cytoskeletal control of RNA fate.\n\nThese molecular activities propagate into specific biological processes. The filament network stabilizes cell architecture and couples to RNA-binding modules, which together regulate ribonucleoprotein assemblies; this causally supports GO:0043488 regulation of mRNA stability and GO:0045727 positive regulation of translation by organizing and protecting transcripts and translation machinery at cytoplasmic sites. The cytoskeletal scaffold also coordinates extracellular matrix production pathways in mesenchymal and epithelial contexts, consistent with GO:0032967 positive regulation of collagen biosynthetic process through cytoskeleton-to-matrix signaling axes. As a stress-responsive scaffold, the filament system modulates innate immune signaling and cytoskeleton-dependent trafficking, explaining GO:0071222 cellular response to lipopolysaccharide and GO:0032495 response to muramyl dipeptide via cytoskeleton-mediated assembly and positioning of signaling complexes.\n\nCellular localization follows directly from the IF architecture and assembly behavior. Filament formation and multivalent binding place the protein in GO:0045111 intermediate filament cytoskeleton. The soluble precursors and dynamic filament assembly occur in the cytoplasm and cytoskeleton, matching the observed cytoplasmic and filamentous distributions.\n\nMechanistically, the head–rod–tail design drives filament assembly that both bears mechanical load and scaffolds regulatory complexes. I hypothesize that the protein forms heteropolymers with other intermediate filament subunits and recruits adaptor/scaffold proteins to tune RNA stability and translation. Likely partners include other IF proteins that co-assemble into mixed networks, chaperones that regulate filament dynamics, and RNA-binding factors that couple the filament lattice to translational control and collagen-producing pathways. This cooperative assembly explains how a cytoskeletal core can influence immune-responsive pathways and matrix biosynthesis while maintaining epithelial and mesenchymal architecture.","category":"control","control_evaluation":{"known_function":"Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally. Plays a role in cell directional movement, orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Protects SCRIB from proteasomal degradation and facilitates its localization to intermediate filaments in a cell contact-mediated manner (By similarity). May promote axon outgrowth and motor fiber repair via DSP-mediated recruitment to outgrowth tips (By similarity) Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2","source":"UniProt P08670, GO annotations (all evidence for \"correct\"; experimental evidence for \"missed\", max 2 per aspect shown)","items":[{"aspect":"Molecular function","known":"molecular adaptor activity · GO:0060090","predicted":"GO:0060090 molecular adaptor activity","verdict":"correct"},{"aspect":"Molecular function","known":"structural constituent of cytoskeleton · GO:0005200","predicted":"GO:0005200 structural constituent of cytoskeleton","verdict":"correct"},{"aspect":"Molecular function","known":"identical protein binding · GO:0042802","predicted":"GO:0042802 identical protein binding","verdict":"correct"},{"aspect":"Molecular function","known":"scaffold protein binding · GO:0097110","predicted":"GO:0097110 scaffold protein binding","verdict":"correct"},{"aspect":"Molecular function","known":"protein domain specific binding · GO:0019904","predicted":"GO:0019904 protein domain specific binding","verdict":"correct"},{"aspect":"Molecular function","known":"double-stranded RNA binding · GO:0003725","predicted":"GO:0003725 double-stranded RNA binding","verdict":"correct"},{"aspect":"Biological process","known":"positive regulation of collagen biosynthetic process · GO:0032967","predicted":"GO:0032967 positive regulation of collagen biosynthetic process","verdict":"correct"},{"aspect":"Biological process","known":"regulation of mRNA stability · GO:0043488","predicted":"GO:0043488 regulation of mRNA stability","verdict":"correct"},{"aspect":"Biological process","known":"cellular response to lipopolysaccharide · GO:0071222","predicted":"GO:0071222 cellular response to lipopolysaccharide","verdict":"correct"},{"aspect":"Biological process","known":"positive regulation of gene expression · GO:0010628","predicted":"GO:0045727 positive regulation of translation","verdict":"correct"},{"aspect":"Biological process","known":"cellular response to muramyl dipeptide · GO:0071225","predicted":"GO:0032495 response to muramyl dipeptide","verdict":"correct"},{"aspect":"Cellular component","known":"intermediate filament cytoskeleton · GO:0045111","predicted":"GO:0045111 intermediate filament cytoskeleton","verdict":"correct"},{"aspect":"Cellular component","known":"cytosol · GO:0005829","predicted":"—","verdict":"missed"},{"aspect":"Cellular component","known":"extracellular exosome · GO:0070062","predicted":"—","verdict":"missed"},{"aspect":"Molecular function","known":"keratin filament binding · GO:1990254","predicted":"—","verdict":"missed"}],"precision":1,"n_missed_exp":6,"n_known_exp":19},"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P08670.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P08670"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P08670/entry","atlas":"/p/P08670"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}