{"uniprot":"Q8TAP6","gene":"CEP76","name":"Centrosomal protein of 76 kDa","organism":"Homo sapiens (Human)","status":"dark","length":659,"sequence":"MSLPPEKASELKQLIHQQLSKMDVHGRIREILAETIREELAPDQQHLSTEDLIKALRRRGIIDDVMKELNFVTDSVEQELPSSPKQPICFDRQSTLKKTNIDPTRRYLYLQVLGGKAFLEHLQEPEPLPGQVCSTFTLCLHYRNQRFRSKPVPCACEPDFHDGFLLEVHRESLGDGTRMADSTTMLSISDPIHMVLIKTDIFGETTLVASYFLEWRSVLGSENGVTSLTVELMGVGTESKVSVGILNIKLEMYPPLNQTLSQEVVNTQLALERQKTAEKERLFLVYAKQWWREYLQIRPSHNSRLVKIFAQDENGINRPVCSYVKPLRAGRLLDTPRQAARFVNVLGYERAPVIGGGGKQEQWCTLLAFLCRNKGDCEDHANLLCSLLLGYGLEAFVCVGTKAKGVPHAWVMTCGTDGAITFWESLTGHRYIHKPTNPDEPPVAEQPKPLYPYRTIGCVFNHQMFLGNCQPSDAVETCVFDLNDESKWKPMSEEAIKSVCAPGATTSLPPFPPLCASTIDASVTSNEIEMQLRLLVSEHRKDLGLTTVWEDQLSYLLSPALASYEFERTTSISAGNEEFQDAIRRAVPDGHTFKGFPIHFVYRNARRAFATCLRSPFCEEIICCRGDQVRLAVRVRVFTYPESACAVWIMFACKYRSVL","function_summary":"A centrosome-localized adaptor that assembles and regulates large protein complexes controlling centriole and centrosome number. Its N-terminal and central interaction modules cooperate with a non-enzymatic peptidase-like scaffold and a dedicated C-terminal targeting region to concentrate soluble pools at centrioles and the centrosome. By organizing multivalent assemblies rather than catalyzing reactions, it fine-tunes pathways that determine whether and how centrioles duplicate and mature, thereby maintaining proper centrosome and centriole copy number.","plain_language":"CEP76 has barely been studied. The model's best guess: A centrosome-localized adaptor that assembles and regulates large protein complexes controlling centriole and centrosome number. Its N-terminal and central interaction modules cooperate with a non-enzymatic peptidase-like scaffold and a dedicated C-terminal targeting region to concentrate soluble pools at centrioles and the centrosome.","uniprot_summary":"Plays a role in centrosome and centriole number control.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0010824","label":"regulation of centrosome duplication"},{"id":"GO:0046599","label":"regulation of centriole replication"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0005814","label":"centriole"},{"id":"GO:0005813","label":"centrosome"}]},"interpro":[{"id":"IPR038765","name":"Papain-like cysteine peptidase superfamily","type":"homologous_superfamily","start":363,"end":412},{"id":"IPR056289","name":"CEP76, N-terminal","type":"domain","start":10,"end":69},{"id":"IPR028926","name":"CEP76, C2 domain","type":"domain","start":100,"end":257},{"id":"IPR056290","name":"CEP76/DRC7, peptidase-like domain","type":"domain","start":361,"end":491},{"id":"IPR056288","name":"Centrosomal protein of 76 kDa, C-terminal","type":"domain","start":518,"end":656},{"id":"IPR052299","name":"Centrosomal protein 76/DOC2","type":"family","start":1,"end":659}],"reasoning":"I begin with the InterPro architecture. The polypeptide starts with IPR056289 (CEP76, N-terminal domain, residues 10–69), followed by a central IPR028926 (CEP76, C2 domain, residues 100–257). The C2 fold typically creates a Ca2+-tunable, acidic-surface–binding module that targets proteins to membrane-proximal or scaffolded cytoskeletal assemblies; in centrosomal proteins, C2 modules often mediate avid, multivalent protein interactions rather than catalysis. The mid-to-C-terminal half contains IPR056290 (CEP76/DRC7, peptidase-like domain, residues 361–491), which overlaps with IPR038765 (Papain-like cysteine peptidase superfamily, residues 363–412). This papain-like scaffold indicates a protease-derived fold but, in many centrosomal regulators, such folds function as non-enzymatic interaction platforms. The extreme C-terminus bears IPR056288 (Centrosomal protein of 76 kDa, C-terminal domain, residues 518–656), a hallmark region that stabilizes centrosome/centriole targeting and complex assembly. The entire sequence is encompassed by IPR052299 (Centrosomal protein 76/DOC2 family, residues 1–659), which unifies the N-terminal and C-terminal targeting modules with a central peptidase-like scaffold into a single centrosomal adaptor framework.\n\nThis ordered layout—an N-terminal targeting module, a central C2 interaction hub, and a C-terminal centrosome-anchoring domain—creates a multivalent scaffold optimized for assembling and modulating large macromolecular assemblies. The absence of catalytic triad annotation in the peptidase-like region and the dominance of interaction-centric modules causally enforce a molecular function centered on multivalent binding rather than enzymatic turnover, aligning with GO:0005515 protein binding.\n\nFrom this binding-centric architecture, the biological role emerges. Centriole copy number control requires precise assembly and disassembly of pericentriolar and centriolar scaffolds. A C2-driven, protease-scaffolded adaptor is well-suited to gate assembly pathways that determine whether procentrioles form and mature. This mechanistic logic supports involvement in GO:0010824 regulation of centrosome duplication and GO:0046599 regulation of centriole replication, where the protein’s scaffold constrains or permits assembly steps that produce daughter centrioles.\n\nCellular placement follows directly. The C-terminal centrosomal domain and the family-wide centrosome targeting collectively position the protein at the microtubule-organizing center. This predicts residence at the GO:0005813 centrosome and specifically at the GO:0005814 centriole, with a soluble pool in the GO:0005829 cytosol that feeds assembly at the organelle. The architecture’s soluble scaffold nature explains cytosolic pools that dynamically exchange with centrosomal structures.\n\nMechanistically, I hypothesize that the C2 domain nucleates assembly at the centriole surface, while the papain-like fold provides a rigid platform that recruits and positions regulatory factors. This scaffold likely tunes centriole duplication by sequestering or presenting assembly determinants and checkpoint cues. In this role, it plausibly engages core centriole duplication machinery and pericentriolar matrix components—such as SASS6, STIL, CEP135, CEP120, and SAS-6—to choreograph cartwheel and stalk assembly, and it may transiently interface with γ-tubulin ring complex elements to modulate microtubule nucleation. Through these interactions, the protein acts as a non-enzymatic centrosomal adaptor that enforces fidelity of centrosome and centriole number.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8TAP6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8TAP6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8TAP6/entry","atlas":"/p/Q8TAP6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}