{"uniprot":"Q1ZZU3","gene":"SWI5","name":"DNA repair protein SWI5 homolog","organism":"Homo sapiens (Human)","status":"dark","length":235,"sequence":"MQRRGQRDLWRHNKSCARNRCPRPPRERGGAGFPWVRAQLSVRQFTLRVRVPGPVHLRGRSPTPALDPLAPLNPLIRGPRTPGLRRWIQSLALLLPNCSSSRIPTVPRPHSGLWVQSDFPLGFLSRTEPRLTRSCRGAFRSPRPLPKSGQADGTSEESLHLDIQKLKEKRDMLDKEISQFVSEGYSVDELEDHITQLHEYNDIKDVGQMLMGKLAVIRGVTTKELYPEFGLDMND","function_summary":"A nuclear chromatin-associated assembly factor that organizes homologous recombination repair after DNA damage. It functions as a non-enzymatic scaffold that binds partner proteins to build the recombination mediator complex on damaged chromatin, thereby promoting strand-exchange repair during the cellular response to ionizing radiation. By stabilizing and coordinating repair assemblies, it ensures efficient double-strand break repair within the nucleus.","plain_language":"SWI5 has barely been studied. The model's best guess: A nuclear chromatin-associated assembly factor that organizes homologous recombination repair after DNA damage. It functions as a non-enzymatic scaffold that binds partner proteins to build the recombination mediator complex on damaged chromatin, thereby promoting strand-exchange repair during the cellular response to ionizing radiation.","uniprot_summary":"Involved in DNA repair by homologous recombination.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0071479","label":"cellular response to ionizing radiation"},{"id":"GO:0000724","label":"double-strand break repair via homologous recombination"}],"cellular_component":[{"id":"GO:0000785","label":"chromatin"},{"id":"GO:0033061","label":"Swi5-Sfr1 complex"}]},"interpro":[{"id":"IPR010760","name":"DNA repair protein, Swi5","type":"family","start":59,"end":235}],"reasoning":"I begin with the InterPro architecture: a single, centrally placed Swi5-family module, IPR010760 (DNA repair protein, Swi5 family) spanning residues 59–235. This family-defining core occupies the bulk of the polypeptide and is characteristic of non-enzymatic DNA repair adaptors that assemble and regulate homologous recombination machinery. The absence of catalytic motifs and the dominance of a repair-scaffold signature indicate a protein whose primary chemistry is macromolecular assembly rather than enzymatic turnover. Such Swi5-family cores typically form obligate heteromeric complexes and bind partner proteins with high specificity, which causally supports a molecular function centered on GO:0005515 protein binding.\n\nFrom this scaffolded Swi5 architecture, the molecular function propagates into homologous recombination pathways. The Swi5 family is a hallmark of the recombination mediator ensemble that activates and coordinates strand-exchange reactions. This architecture drives assembly of repair complexes that stabilize single-stranded DNA and promote presynaptic filament formation, thereby enforcing GO:0000724 double-strand break repair via homologous recombination. Because ionizing radiation generates DNA double-strand breaks and funnels repair into homologous pathways, a Swi5-centered scaffold naturally operates during the cellular response to ionizing radiation, aligning with GO:0071479 cellular response to ionizing radiation.\n\nCellular placement follows from function and binding mode. Homologous recombination occurs on chromatinized templates; thus a Swi5-family scaffold that organizes recombination assemblies is expected to reside on chromatin and within nuclear repair condensates. This reasoning anchors the protein in GO:0000785 chromatin and in the dedicated GO:0033061 Swi5-Sfr1 complex, the canonical mediator assembly that nucleates HR machinery. The experimentally observed nuclear localization is consistent with this chromatin-bound nuclear complex.\n\nMechanistically, the Swi5-family core causes formation of a mediator complex that binds and stabilizes HR factors on damaged chromatin. I hypothesize that the protein hetero-oligomerizes with its Sfr1 partner to form the Swi5-Sfr1 complex, which then recruits and stimulates downstream HR modules. Likely partners include recombinase loaders and ssDNA-stabilizing factors; through multivalent protein binding, the complex concentrates and activates HR at sites of radiation-induced breaks, ensuring efficient strand invasion and repair completion within the nuclear chromatin environment.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q1ZZU3.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q1ZZU3"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q1ZZU3/entry","atlas":"/p/Q1ZZU3"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}