{"uniprot":"Q6IQ16","gene":"SPOPL","name":"Speckle-type POZ protein-like","organism":"Homo sapiens (Human)","status":"dark","length":392,"sequence":"MSREPTPPLPGDMSTGPIAESWCYTQVKVVKFSYMWTINNFSFCREEMGEVLKSSTFSSGPSDKMKWCLRVNPKGLDDESKDYLSLYLLLVSCPKSEVRAKFKFSLLNAKREETKAMESQRAYRFVQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQDSVNISGHTNTNTLKVPECRLAEDLGNLWENTRFTDCSFFVRGQEFKAHKSVLAARSPVFNAMFEHEMEESKKNRVEINDLDPEVFKEMMRFIYTGRAPNLDKMADNLLAAADKYALERLKVMCEEALCSNLSVENVADTLVLADLHSAEQLKAQAIDFINRCSVLRQLGCKDGKNWNSNQATDIMETSGWKSMIQSHPHLVAEAFRALASAQCPQFGIPRKRLKQS","function_summary":"A human adaptor that organizes ubiquitination signaling by coupling an N-terminal substrate-recognition module to a C-terminal cullin-docking module. It assembles higher-order complexes that recruit targets and position them within a cullin–RING ligase to drive proteasome-dependent turnover, while its multivalent binding surface can also attenuate specific ubiquitination events. Operating within cullin-based ligase assemblies that function in both cytoplasm and nucleus, it acts as a scaffold that balances substrate capture with controlled ubiquitin pathway flux.","plain_language":"SPOPL has barely been studied. The model's best guess: A human adaptor that organizes ubiquitination signaling by coupling an N-terminal substrate-recognition module to a C-terminal cullin-docking module. It assembles higher-order complexes that recruit targets and position them within a cullin–RING ligase to drive proteasome-dependent turnover, while its multivalent binding surface can also attenuate specific ubiquitination events.","uniprot_summary":"Probable adapter protein.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0043161","label":"proteasome-mediated ubiquitin-dependent protein catabolic process"},{"id":"GO:0031397","label":"negative regulation of protein ubiquitination"}],"cellular_component":[{"id":"GO:0031463","label":"Cul3-RING ubiquitin ligase complex"}]},"interpro":[{"id":"IPR008974","name":"TRAF-like","type":"homologous_superfamily","start":29,"end":166},{"id":"IPR011333","name":"SKP1/BTB/POZ domain superfamily","type":"homologous_superfamily","start":175,"end":295},{"id":"IPR002083","name":"MATH/TRAF domain","type":"domain","start":31,"end":161},{"id":"IPR000210","name":"BTB/POZ domain","type":"domain","start":191,"end":297}],"reasoning":"I begin with the domain architecture. The N-terminal half contains IPR008974 (TRAF-like homologous superfamily, residues 29–166) and, nested within it, IPR002083 (MATH/TRAF domain, residues 31–161). A MATH/TRAF fold is a canonical trimerizing β-sandwich used by TRAF adaptors to bind short linear motifs in signaling proteins; this architecture enforces multivalent protein–protein interactions rather than catalysis. The C-terminal half transitions into IPR011333 (SKP1/BTB/POZ domain superfamily, residues 175–295) and the embedded IPR000210 (BTB/POZ domain, residues 191–297). BTB/POZ domains form obligate dimers that dock onto CUL3 to assemble cullin–RING E3 ligase (CRL) complexes. The ordered layout—N-terminal MATH/TRAF for substrate/adaptor capture followed by a C-terminal BTB/POZ cullin-docking module—creates a bipartite scaffold that binds multiple partners and positions them within a CRL assembly.\n\nThis architecture dictates the molecular function. The MATH/TRAF and BTB/POZ modules together create a multivalent hub that binds proteins avidly and organizes them into higher-order assemblies. This directly supports GO:0005515 protein binding as the operative molecular function: neither domain imparts enzymatic chemistry itself, but they impose specificity and avidity for assembling signaling and ubiquitination machinery.\n\nFrom this binding-centric core, the biological processes follow. The BTB/POZ-mediated engagement of CUL3 places the protein inside a CRL, which drives GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process by recruiting substrates and catalyzing their ubiquitin-dependent turnover. At the same time, the MATH/TRAF module can act as a regulatory adaptor that tunes ubiquitin pathway flux. By sequestering substrates or modulating E3/E2 access, the scaffold can attenuate ubiquitination events, aligning with GO:0031397 negative regulation of protein ubiquitination. The dual capacity—assembly of CRL and selective substrate capture—explains how the same molecule both promotes proteasomal pathways and restrains specific ubiquitin reactions.\n\nCellular location is implied by the assembly it builds. The BTB/POZ domain recruits CUL3 and RBX1 to form a Cul3-RING ubiquitin ligase core, situating the protein in GO:0031463 Cul3-RING ubiquitin ligase complex. Such complexes operate in both cytoplasm and nucleus, where substrate selection and proteasome-coupled turnover are coordinated; the soluble, adaptor-centric architecture supports dynamic shuttling between these compartments.\n\nMechanistically, the N-terminal MATH/TRAF domain captures signaling or cytoskeletal substrates and adaptor proteins, forming trimeric or higher-order assemblies that concentrate targets. The C-terminal BTB/POZ domain dimerizes and binds CUL3, positioning RBX1 and E2 enzymes to transfer ubiquitin. This causes efficient substrate handoff to the proteasome while allowing selective dampening of ubiquitination through competitive binding or transient sequestration. Likely interaction partners include core CRL components (CUL3 and RBX1), exchangeable E2s (e.g., UBE2D family), and substrate cohorts stabilized by TRAF-like recognition motifs; together these interactions produce a tunable ubiquitin-signaling hub that couples substrate selection to proteasomal degradation.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q6IQ16.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q6IQ16"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q6IQ16/entry","atlas":"/p/Q6IQ16"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}