{"uniprot":"Q8N3X1","gene":"FNBP4","name":"Formin-binding protein 4","organism":"Homo sapiens (Human)","status":"dark","length":1017,"sequence":"MGKKSRAVPGRRPILQLSPPGPRGSTPGRDPEPEPDTEPDSTAAVPSQPAPSAATTTTTAVTAAAASDDSPSEDEQEAVQEVPRVVQNPPKPVMTTRPTAVKATGGLCLLGAYADSDDDDNDVSEKLAQSKETNGNQSTDIDSTLANFLAEIDAITAPQPAAPVGASAPPPTPPRPEPKEAATSTLSSSTSNGTDSTQTSGWQYDTQCSLAGVGIEMGDWQEVWDENTGCYYYWNTQTNEVTWELPQYLATQVQGLQHYQPSSVPGAETSFVVNTDIYSKEKTISVSSSKSGPVIAKREVKKEVNEGIQALSNSEEEKKGVAASLLAPLLPEGIKEEEERWRRKVICKEEPVSEVKETSTTVEEATTIVKPQEIMLDNIEDPSQEDLCSVVQSGESEEEEEQDTLELELVLERKKAELRALEEGDGSVSGSSPRSDISQPASQDGMRRLMSKRGKWKMFVRATSPESTSRSSSKTGRDTPENGETAIGAENSEKIDENSDKEMEVEESPEKIKVQTTPKVEEEQDLKFQIGELANTLTSKFEFLGINRQSISNFHVLLLQTETRIADWREGALNGNYLKRKLQDAAEQLKQYEINATPKGWSCHWDRDHRRYFYVNEQSGESQWEFPDGEEEEEESQAQENRDETLAKQTLKDKTGTDSNSTESSETSTGSLCKESFSGQVSSSSLMPLTPFWTLLQSNVPVLQPPLPLEMPPPPPPPPESPPPPPPPPPPAEDGEIQEVEMEDEGSEEPPAPGTEEDTPLKPSAQTTVVTSQSSVDSTISSSSSTKGIKRKATEISTAVVQRSATIGSSPVLYSQSAIATGHQAAGIGNQATGIGHQTIPVSLPAAGMGHQARGMSLQSNYLGLAAAPAIMSYAECSVPIGVTAPSLQPVQARGAVPTATIIEPPPPPPPPPPPPPPAPKMPPPEKTKKGRKDKAKKSKTKMPSLVKKWQSIQRELDEEDNSSSSEEDRESTAQKRIEEWKQQQLVSGMAERNANFEALPEDWRARLKRRKMAPNT","function_summary":"A large human nuclear scaffold that concentrates RNA-processing machinery within nuclear speckles. Through tandem WW modules and extensive low-complexity regions, it assembles and stabilizes macromolecular complexes that coordinate pre-mRNA maturation. By organizing spliceosome-associated factors in speckle compartments, it modulates mRNA splicing efficiency and fidelity, with potential coupling to actin/formin-linked pathways that influence nuclear speck architecture and RNA-processing dynamics.","plain_language":"FNBP4 has barely been studied. The model's best guess: A large human nuclear scaffold that concentrates RNA-processing machinery within nuclear speckles. Through tandem WW modules and extensive low-complexity regions, it assembles and stabilizes macromolecular complexes that coordinate pre-mRNA maturation.","uniprot_summary":"May be involved in mRNA splicing.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0000398","label":"mRNA splicing, via spliceosome"}],"cellular_component":[{"id":"GO:0016607","label":"nuclear speck"}]},"interpro":[{"id":"IPR036020","name":"WW domain superfamily","type":"homologous_superfamily","start":212,"end":248},{"id":"IPR036020","name":"WW domain superfamily","type":"homologous_superfamily","start":591,"end":628},{"id":"IPR001202","name":"WW domain","type":"domain","start":215,"end":248},{"id":"IPR001202","name":"WW domain","type":"domain","start":595,"end":629},{"id":"IPR053076","name":"Formin-binding protein 4","type":"family","start":1,"end":1017}],"reasoning":"I begin with the InterPro architecture. The sequence is assigned to IPR053076 (Formin-binding protein 4 family) spanning residues 1–1017, marking the entire polypeptide as a member of the FBp4 family that typically functions as a large nuclear scaffold. Two WW modules are present: an N-terminal WW domain IPR001202 (WW domain, residues 215–248) embedded within IPR036020 (WW domain superfamily, residues 212–248), and a C-terminal WW domain IPR001202 (WW domain, residues 595–629) embedded within IPR036020 (WW domain superfamily, residues 591–628). WW domains are compact β-sheet modules that bind proline-rich and PPxY-containing motifs and often mediate assembly of macromolecular complexes. The tandem arrangement—an N-terminal WW domain followed by a C-terminal WW domain—creates a multivalent binding platform separated by a long central region that can organize additional low-complexity or coiled interfaces. This architecture causes broad protein-binding capacity rather than enzymatic catalysis, aligning with GO:0005515 protein binding as the molecular function.\n\nWW-domain scaffolds frequently operate in nuclear RNA-processing assemblies. The FBp4 family signature and the dual WW modules together predict avid assembly of ribonucleoprotein complexes that regulate pre-mRNA maturation. Such scaffolding is well-suited to concentrate spliceosomal and splicing-regulatory factors, which mechanistically supports involvement in GO:0000398 mRNA splicing, via spliceosome. The presence of two distinct WW modules enables simultaneous capture of multiple proline-rich ligands, stabilizing spliceosome-associated hubs and tuning splice-site selection.\n\nCellular localization follows from function and architecture. Proteins that scaffold spliceosome-associated assemblies typically reside in nuclear speckles—dynamic, phase-separated compartments that store and exchange splicing factors. The WW-domain-driven multivalency and the FBp4 family context together predict accumulation in nuclear speckles, consistent with GO:0016607 nuclear speck. This nuclear speck residence explains how the protein encounters and coordinates splicing machinery in a spatially organized nuclear environment.\n\nMechanistically, I hypothesize that the N-terminal WW domain nucleates initial contacts with PPxY/proline-rich partners, while the C-terminal WW domain stabilizes higher-order assemblies, collectively concentrating spliceosomal components and auxiliary regulators within speckles. The formin-binding ancestry of the family suggests a regulatory bridge between actin/formin signaling and nuclear RNA processing—potentially via transient interactions with nuclear actin or formin-derived pathways that influence speck architecture and mRNA maturation.\n\nFrom this model, likely interaction partners include speckle-resident splicing factors and adaptors that present WW-compatible motifs. Candidates include serine/arginine-rich splicing regulators (e.g., SRSF family), U2AF and SF3 complexes, and speckle organizers such as SON and SRRM2. Transient contacts with nuclear actin and formin-related adaptors could couple cytoskeletal cues to nuclear speck dynamics, fine-tuning spliceosome assembly and function.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N3X1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N3X1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N3X1/entry","atlas":"/p/Q8N3X1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}