{"uniprot":"B1AJZ9","gene":"FHAD1","name":"Forkhead-associated domain-containing protein 1","organism":"Homo sapiens (Human)","status":"dark","length":1412,"sequence":"MKAYLKSAEGFFVLNKSTTIGRHENSDLVLQSPDIDNHHALIEYNEAECSFVLQDFNSRNGTFVNECHIQNVAVKLIPGDILRFGSAGLTYELVIENPPPVSFPWMRGPAPWPGPQPPRATQQPNQAPPPSHIPFHQGVQPAPMQRSWSQAFPRPTVVLPASHRRPVSANKEMFSFVVDDARKPPVIKQVWTNAMKLSEKSVAEGIPGAVPPAEIYVEEDLAQQDKDEIILLLGKEVSRLSDYEIESKYKDVIIANLQNEVAELSQKVSETTTSRQNEKEISQKCQVLDEDIDAKQKEIQSLKSQISALQKGYSKVLCQTLSERNSEITSLKNEGENLKRDNAITSGMVSSLQKDILAKDEQVQQLKEEVSHLKSQNKDKDHQLEALGSRCSVLKEELKQEDAHRELREAQEKELKLCKTQIQDMEKEMKKLRAELRKSCTEQSVISRTLREKSKVEEKLQEDSRRKLLQLQEMGNRESVIKINLERAVGQLEHFRSQVIKATYGRAKPFRDKPVTDQQLIEKITQVTEDNINFQQKKWTLQKETQLSNSKQEETTENIEKLRTSLDSCQACMKISCCSHDLKKEVDLLQHLQVSPPVSGLQKVVLDVLRHALSWLEEVEQLLRDLGILPSSPNKDQVQQFSGNSAVFTAGKAAGASGREGEAERGEARARGEAQSQNQATDGREGGKALEEYITQERNRAKETLEEERKRMQELESLLAQQKKALAKSITQEKNRVKEALEEEQTRVQELEERLARQKEVLESSIAHEKRKAKEALESEKRKVQDLENHLTQQKEISESNIAYEKRKAKEAMEKEKKKVQDLENRLTKQKEELELKEQKEDVLNNKLSDALAMVEETQKTKATESLKAESLALKLNETLAELETTKTKMIMVEERLILQQKMVKALQDEQESQRHGFEEEIMEYKEQIKQHAQTIVSLEEKLQKVTQHHKKIEGEIATLKDNDPAPKEERPQDPLVAPMTESSAKDMAYEHLIDDLLAAQKEILSQQEVIMKLRKDLTEAHSRMSDLRGELNEKQKMELEQNVVLVQQQSKELSVLKEKMAQMSSLVEKKDRELKALEEALRASQEKHRLQLNTEKEQKPRKKTQTCDTSVQIEPVHTEAFSSSQEQQSFSDLGVRCKGSRHEEVIQRQKKALSELRARIKELEKARSPDHKDHQNESFLDLKNLRMENNVQKILLDAKPDLPTLSRIEILAPQNGLCNARFGSAMEKSGKMDVAEALELSEKLYLDMSKTLGSLMNIKNMSGHVSMKYLSRQEREKVNQLRQRDLDLVFDKITQLKNQLGRKEELLRGYEKDVEQLRRSKVSIEMYQSQVAKLEDDIYKEAEEKALLKEALERMEHQLCQEKRINRAIRQQKVGTRKASLKMDQEREMLRKETSSKSSQSLLHSKPSGKY","function_summary":"A human centrosome-associated scaffold that combines an N-terminal phospho-recognition module with a large coiled-coil body to assemble signaling and structural complexes. By binding phosphorylated partners and oligomerizing into higher-order assemblies, it coordinates centrosomal architecture with transcriptional programs that drive the G1/S transition. This coupling of a phospho-sensing head and a coiled-coil tail enables regulated protein interactions that promote RNA polymerase II–dependent transcription while positioning the complex at the centrosome.","plain_language":"FHAD1 has barely been studied. The model's best guess: A human centrosome-associated scaffold that combines an N-terminal phospho-recognition module with a large coiled-coil body to assemble signaling and structural complexes. By binding phosphorylated partners and oligomerizing into higher-order assemblies, it coordinates centrosomal architecture with transcriptional programs that drive the G1/S transition.","uniprot_summary":"May be involved in transcription regulation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0000083","label":"regulation of transcription involved in G1/S transition of mitotic cell cycle"},{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II"}],"cellular_component":[{"id":"GO:0005813","label":"centrosome"}]},"interpro":[{"id":"IPR008984","name":"SMAD/FHA domain superfamily","type":"homologous_superfamily","start":11,"end":95},{"id":"IPR000253","name":"Forkhead-associated (FHA) domain","type":"domain","start":17,"end":85},{"id":"IPR060375","name":"CCDC27/FHAD1, coiled-coil","type":"domain","start":278,"end":537},{"id":"IPR052642","name":"Coiled-coil and Forkhead-associated domain-containing protein","type":"family","start":1,"end":563}],"reasoning":"I begin with the domain architecture. The N-terminus carries IPR008984 (SMAD/FHA domain superfamily, residues 11–95), within which sits a well-defined IPR000253 FHA domain (residues 17–85). FHA modules are phosphothreonine-recognition folds that create regulated protein–protein interfaces, typically wiring checkpoint and cell-cycle signaling. The C-terminal half is dominated by IPR060375 (CCDC27/FHAD1, coiled-coil, residues 278–537), a predicted oligomerization scaffold that stabilizes higher-order assemblies. The entire polypeptide is encompassed by IPR052642 (Coiled-coil and Forkhead-associated domain-containing protein family, residues 1–563), indicating a conserved bipartite design: an N-terminal phospho-sensor FHA domain followed by an extended coiled-coil tail that mediates multivalent assembly. This architecture causally enforces protein-binding capacity through two complementary surfaces—an FHA phospho-reader and a coiled-coil oligomerization platform—supporting GO:0005515 protein binding as the molecular function.\n\nFrom this molecular scaffold, I infer process-level roles. FHA domains frequently gate cell-cycle transitions by decoding phosphorylation at centrosomes and kinetochores. The presence of a long coiled-coil region suggests a structural hub that recruits and stabilizes pericentriolar complexes. Such assemblies are well-suited to coordinate transcriptional regulators that drive entry into S phase. This mechanistic coupling explains participation in GO:0000083 regulation of transcription involved in G1/S transition of the mitotic cell cycle and GO:0045944 positive regulation of transcription by RNA polymerase II: the FHA domain senses phosphorylation cues, while the coiled-coil tail nucleates assemblies that potentiate transcriptional programs necessary for G1/S.\n\nCellular localization follows directly from the assembly logic. A phospho-sensing FHA head tethered to a large coiled-coil body is optimized for pericentriolar matrix scaffolding and cell-cycle signaling nodes. This predicts residence at the GO:0005813 centrosome, consistent with a role in organizing microtubule-organizing centers and coordinating mitotic entry.\n\nMechanistically, I hypothesize that the FHA domain captures phosphorylated partners during cell-cycle transitions, while the coiled-coil region oligomerizes to build a centrosomal scaffold that both senses and transmits checkpoint signals. This scaffold likely recruits centrosomal organizers and transcriptional regulators to synchronize structural cell-cycle events with gene expression. Likely partners include centrosomal matrix proteins and checkpoint kinases that provide phospho-motifs for FHA engagement, as well as transcriptional coactivators that amplify RNA polymerase II–driven programs at the G1/S boundary.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-B1AJZ9.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/B1AJZ9"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/B1AJZ9/entry","atlas":"/p/B1AJZ9"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}