{"uniprot":"Q96MR6","gene":"CFAP57","name":"Cilia- and flagella-associated protein 57","organism":"Homo sapiens (Human)","status":"dark","length":1250,"sequence":"MSAVVAQTLHVFGLRSHVANNIFYFDEQIIIFPSGNHCVKYNVDQKWQKFIPGSEKSQGMLALSISPNRRYLAISETVQEKPAITIYELSSIPCRKRKVLNNFDFQVQKFISMAFSPDSKYLLAQTSPPESNLVYWLWEKQKVMAIVRIDTQNNPVYQVSFSPQDNTQVCVTGNGMFKLLRFAEGTLKQTSFQRGEPQNYLAHTWVADDKIVVGTDTGKLFLFESGDQRWETSIMVKEPTNGSKSLDVIQESESLIEFPPVSSPLPSYEQMVAASSHSQMSMPQVFAIAAYSKGFACSAGPGRVLLFEKMEEKDFYRESREIRIPVDPQSNDPSQSDKQDVLCLCFSPSEETLVASTSKNQLYSITMSLTEISKGEPAHFEYLMYPLHSAPITGLATCIRKPLIATCSLDRSIRLWNYETNTLELFKEYQEEAYSISLHPSGHFIVVGFADKLRLMNLLIDDIRSFKEYSVRGCGECSFSNGGHLFAAVNGNVIHVYTTTSLENISSLKGHTGKIRSIVWNADDSKLISGGTDGAVYEWNLSTGKRETECVLKSCSYNCVTVSPDAKIIFAVGSDHTLKEIADSLILREISAFDVTYTAIVISHSGRMMFVGTSVGTIRAMKYPLPLQKEFNEYQAHAGPITKMLLTFDDQFLLTAAEDGCLFTWKVFDKDGRGIKREREVGFAEEVLVTKTDMEEKAQVMLELKTRVEELKMENEYQLRLKDMNYSEKIKELTDKFIQEMESLKTKNQVLRTEKEKQDVYHHEHIEDLLDKQSRELQDMECCNNQKLLLEYEKYQELQLKSQRMQEEYEKQLRDNDETKSQALEELTEFYEAKLQEKTTLLEEAQEDVRQQLREFEETKKQIEEDEDREIQDIKTKYEKKLRDEKESNLRLKGETGIMRKKFSSLQKEIEERTNDIETLKGEQMKLQGVIKSLEKDIQGLKREIQERDETIQDKEKRIYDLKKKNQELGKFKFVLDYKIKELKKQIEPRENEIRVMKEQIQEMEAELENFHKQNTQLELNITELWQKLRATDQEMRRERQKERDLEALVKRFKTDLHNCVAYIQEPRLLKEKVRGLFEKYVQRADMVEIAGLNTDLQQEYTRQREHLERNLATLKKKVVKEGELHRTDYVRIMQENVSLIKEINELRRELKFTRSQVYDLEAALKLTKKVRPQEVSETEPSRDMLSTAPTARLNEQEETGRIIEMQRLEIQRLRDQIQEQEQVTGFHTLAGVRLPSLSNSEVDLEVKTN","function_summary":"A human cilia/flagella-associated scaffold that uses tandem beta-propeller modules to organize multiprotein assemblies at the base of motile cilia and sperm flagella. By concentrating and stabilizing axonemal and peri-axonemal complexes, it supports efficient assembly and maintenance of the cilium/flagellum system and thereby promotes sperm motility. Its multivalent binding surfaces favor cooperative interactions with basal-body and transport machinery, positioning the protein as a hub that couples structural assembly to motility.","plain_language":"CFAP57 has barely been studied. The model's best guess: A human cilia/flagella-associated scaffold that uses tandem beta-propeller modules to organize multiprotein assemblies at the base of motile cilia and sperm flagella. By concentrating and stabilizing axonemal and peri-axonemal complexes, it supports efficient assembly and maintenance of the cilium/flagellum system and thereby promotes sperm motility.","uniprot_summary":"May play a role in flagellar and cilia assembly and/or maintenance.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0030317","label":"flagellated sperm motility"}],"cellular_component":[{"id":"GO:0036064","label":"ciliary basal body"}]},"interpro":[{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":16,"end":256},{"id":"IPR011047","name":"Quinoprotein alcohol dehydrogenase-like superfamily","type":"homologous_superfamily","start":195,"end":671},{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":373,"end":668},{"id":"IPR055442","name":"EML-like, second beta-propeller domain","type":"domain","start":393,"end":667},{"id":"IPR052993","name":"Cilia- and flagella-associated protein 57","type":"family","start":8,"end":1230},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":140,"end":181},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":330,"end":367},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":378,"end":457},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":501,"end":582},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":627,"end":667}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the polypeptide. The N-terminal half is dominated by IPR015943 (WD40/YVTN repeat-like-containing domain superfamily, residues 16–256), which establishes a β-propeller scaffold early in the sequence. This assignment is reinforced by multiple discrete WD40 repeats: IPR001680 (WD40 repeat, residues 140–181), IPR001680 (WD40 repeat, residues 330–367), IPR001680 (WD40 repeat, residues 378–457), and IPR001680 (WD40 repeat, residues 501–582). A second β-propeller system is specified by IPR055442 (EML-like, second beta-propeller domain, residues 393–667) and again by IPR015943 (WD40/YVTN repeat-like-containing domain superfamily, residues 373–668), indicating tandem β-propeller modules that together create a multivalent binding platform. The central-to-C-terminal region also carries IPR011047 (Quinoprotein alcohol dehydrogenase-like superfamily, residues 195–671), a structural superfamily that frequently adopts β-propeller or β-sandwich folds rather than catalytic chemistry here; this supports a non-enzymatic, interaction-centric role. The entire protein is classified within IPR052993 (Cilia- and flagella-associated protein 57 family, residues 8–1230), tying this scaffold to ciliary and flagellar systems.\n\nThis tandem β-propeller architecture causes high-capacity protein binding rather than enzymatic turnover, aligning with GO:0005515 protein binding as the molecular function. WD40 β-propellers typically mediate assembly of large macromolecular complexes by presenting radial surfaces for docking multiple partners; the presence of two EML-like β-propellers suggests cooperative avidity and specificity suited to cytoskeletal and membrane-associated assemblies.\n\nFrom this binding-centric core, I infer the biological process by considering where such scaffolds operate and to what end. The family-level signature (IPR052993) and the localization logic point to cilia/flagella. In sperm, the axoneme and associated complexes drive waveform generation; a multivalent scaffold that concentrates and stabilizes axonemal and peri-axonemal components naturally promotes efficient beat mechanics. This causal chain—tandem β-propellers assembling axonemal modules—supports the process formalized as GO:0030317 flagellated sperm motility.\n\nCellular placement follows from both architecture and labels. The CC evidence converges on the ciliary apparatus: GO:0036064 ciliary basal body and the broader subcellular descriptors point to the cilium and flagellum. A basal-body-associated scaffold that traffics or anchors complexes at the base of the axoneme explains how the protein coordinates assembly and maintenance of the motile cilium/flagellum system in human cells.\n\nMechanistically, I hypothesize that the N-terminal β-propeller nucleates initial assemblies at the basal body, while the C-terminal EML-like β-propeller refines partner selection and stabilizes higher-order complexes. This two-propeller tandem likely recruits intraflagellar transport adaptors and axonemal regulators to tune dynein-driven beating. Consequently, the protein is poised to interact with basal-body organizers and IFT machinery, coupling structural assembly to motility outputs.\n\nTo synthesize: the WD40-rich, tandem β-propeller scaffold (IPR015943; IPR055442; IPR011047; multiple IPR001680 repeats) dictates a multivalent binding hub (GO:0005515) that assembles and stabilizes ciliary/flagellar modules, driving flagellated sperm motility (GO:0030317) and operating at the ciliary basal body (GO:0036064) within the cilium/flagellum system. Likely partners include basal-body and IFT components that together orchestrate axonemal assembly and function.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96MR6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96MR6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96MR6/entry","atlas":"/p/Q96MR6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}