{"uniprot":"A0A1W2PR48","gene":"TLE7","name":"Transducin-like enhancer protein 7","organism":"Homo sapiens (Human)","status":"dark","length":441,"sequence":"MSGEKEEASLRMFGAYGEPEERRDVLESSGVSSQPEPQVQQQLGSLLGVPWQPPGPPIQHSPADQETSTVTQQQWHLQGLGRSELQAAGLPDAQPGEAAESSPSFLLGSEVGQPYSSSSPSEEVLSLLRAIPPIPDEVVVRQKRAPQGSWKVGTLFHGKRVYAVAISGSTHHVYTCGSGYIRVWDESALHAGEKAPRAQLDLQHPQDRVVTCKLFPDERSLITGGASQAVTLWDLAPTPQVRAQLTSTGPTCYSLAVSSDAHICLACFHGFVEIWDLQNQILIRKHEVPVYGSRCVDITGNIFWTGGEDTILYSWDLRSYQRLHQHNLQNEILSITHDPGEEWVLAGLRTSDIVFLHTRRNEQFKALMKKYTRHHSLKFASCGSYFVTAIDTRLSGLEAPSLQKLFQIEESSGILCCDVSSDNQYLVMGSSSSATIYQLLY","function_summary":"A human β-propeller scaffold that assembles transcriptional regulatory complexes. Its WD40-based architecture organizes transcription factors and chromatin-modifying enzymes to modulate RNA polymerase II–dependent gene expression, enabling both repression and activation depending on partner composition. The complex pools in the cytoplasm and nucleus and can transiently accumulate at the intercellular bridge during cytokinesis, reflecting a role in assembling and localizing macromolecular modules that fine-tune transcriptional programs.","plain_language":"TLE7 has barely been studied. The model's best guess: A human β-propeller scaffold that assembles transcriptional regulatory complexes. Its WD40-based architecture organizes transcription factors and chromatin-modifying enzymes to modulate RNA polymerase II–dependent gene expression, enabling both repression and activation depending on partner composition.","uniprot_summary":"May be involved in transcriptional regulation.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006357","label":"regulation of transcription by RNA polymerase II"},{"id":"GO:0034504","label":"protein localization to nucleus"},{"id":"GO:0045944","label":"positive regulation of transcription by RNA polymerase II"}],"cellular_component":[{"id":"GO:0032991","label":"protein-containing complex"},{"id":"GO:0045171","label":"intercellular bridge"},{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0005634","label":"nucleus"}]},"interpro":[{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":120,"end":441},{"id":"IPR036322","name":"WD40-repeat-containing domain superfamily","type":"homologous_superfamily","start":148,"end":432},{"id":"IPR009146","name":"Groucho/transducin-like enhancer","type":"family","start":78,"end":441},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":148,"end":185},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":195,"end":276},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":277,"end":316},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":401,"end":438}],"reasoning":"I begin with the InterPro architecture. The core of the protein is a WD40/YVTN β-propeller scaffold: IPR015943 (WD40/YVTN repeat-like-containing domain superfamily, residues 120–441) and IPR036322 (WD40-repeat-containing domain superfamily, residues 148–432) together define a multi-bladed β-propeller platform optimized for assembling macromolecular complexes rather than catalysis. This scaffold is reinforced by multiple discrete WD40 repeats: IPR001680 WD40 repeat elements occur at residues 148–185, 195–276, 277–316, and 401–438, indicating a complete propeller with several blades that create shallow binding grooves for partner proteins. The broader family signature IPR009146 (Groucho/transducin-like enhancer family, residues 78–441) situates this β-propeller within the Groucho/TLE lineage of transcriptional coregulators. This ordered layout—an N-terminal family-defining region feeding into a C-terminal WD40 propeller—causes high-affinity, multivalent protein binding and complex assembly, directly supporting GO:0005515 protein binding as the molecular function.\n\nA WD40-based Groucho/TLE scaffold typically operates as a transcriptional coregulator by docking transcription factors and chromatin-modifying enzymes. This architecture enables both repression and activation depending on context: when it stabilizes repressor assemblies, it dampens transcription; when it nucleates activator assemblies or recruits coactivator machinery, it can enhance transcription. This dual regulatory logic explains participation in GO:0006357 regulation of transcription by RNA polymerase II and specifically aligns with GO:0045944 positive regulation of transcription by RNA polymerase II when the scaffold favors activation-competent complexes. The same β-propeller surface that organizes transcriptional modules also binds transport and localization factors, providing a mechanistic basis for GO:0034504 protein localization to nucleus—either by ferrying transcriptional machinery to the nucleus or stabilizing nuclear complexes that drive nuclear accumulation.\n\nCellular localization follows from function and architecture. WD40 scaffolds of the Groucho/TLE family assemble nuclear complexes, consistent with GO:0005634 nucleus. Yet coregulator pools often shuttle and preassemble in the cytoplasm before nuclear import, matching GO:0005737 cytoplasm. The propensity to form higher-order assemblies via the β-propeller explains residence within GO:0032991 protein-containing complex. During late mitosis and cytokinesis, transcriptional and cytoskeletal assemblies converge at the midbody; a modular scaffold that binds diverse partners can transiently accumulate at the GO:0045171 intercellular bridge, where it may coordinate abscission-associated signaling and subsequent transcriptional reset.\n\nMechanistically, I hypothesize that this protein acts as a context-dependent transcriptional organizer. Its WD40 propeller creates a hub that captures sequence-specific transcription factors and chromatin regulators, toggling between repression and activation. In the nucleus, it likely stabilizes RNAPII-associated assemblies and chromatin remodelers to fine-tune gene expression; in the cytoplasm and at the intercellular bridge, it transiently scaffolds transport and cytokinesis modules that feed back into nuclear transcriptional programs. Likely partners include DNA-bound repressors/activators and chromatin-modifying enzymes that together determine whether the assembled complex promotes or restrains transcriptional output.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-A0A1W2PR48.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/A0A1W2PR48"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/A0A1W2PR48/entry","atlas":"/p/A0A1W2PR48"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}