{"uniprot":"Q32P44","gene":"EML3","name":"Echinoderm microtubule-associated protein-like 3","organism":"Homo sapiens (Human)","status":"dark","length":896,"sequence":"MDGAAGPGDGPAREALQSLSQRLRVQEQEMELVKAALAEALRLLRLQVPPSSLQGSGTPAPPGDSLAAPPGLPPTCTPSLVSRGTQTETEVELKSSPGPPGLSNGPPAPQGASEEPSGTQSEGGGSSSSGAGSPGPPGILRPLQPPQRADTPRRNSSSSSSPSERPRQKLSRKAISSANLLVRSGSTESRGGKDPLSSPGGPGSRRSNYNLEGISVKMFLRGRPITMYIPSGIRSLEELPSGPPPETLSLDWVYGYRGRDSRSNLFVLRSGEVVYFIACVVVLYRPGGGPGGPGGGGQRHYRGHTDCVRCLAVHPDGVRVASGQTAGVDKDGKPLQPVVHIWDSETLLKLQEIGLGAFERGVGALAFSAADQGAFLCVVDDSNEHMLSVWDCSRGMKLAEIKSTNDSVLAVGFNPRDSSCIVTSGKSHVHFWNWSGGVGVPGNGTLTRKQGVFGKYKKPKFIPCFVFLPDGDILTGDSEGNILTWGRSPSDSKTPGRGGAKETYGIVAQAHAHEGSIFALCLRRDGTVLSGGGRDRRLVQWGPGLVALQEAEIPEHFGAVRAIAEGLGSELLVGTTKNALLRGDLAQGFSPVIQGHTDELWGLCTHPSQNRFLTCGHDRQLCLWDGESHALAWSIDLKETGLCADFHPSGAVVAVGLNTGRWLVLDTETREIVSDVIDGNEQLSVVRYSPDGLYLAIGSHDNVIYIYSVSSDGAKSSRFGRCMGHSSFITHLDWSKDGNFIMSNSGDYEILYWDVAGGCKQLKNRYESRDREWATYTCVLGFHVYGVWPDGSDGTDINSLCRSHNERVVAVADDFCKVHLFQYPCARAKAPSRMYGGHGSHVTSVRFTHDDSHLVSLGGKDASIFQWRVLGAGGAGPAPATPSRTPSLSPASSLDV","function_summary":"A soluble cytoskeletal scaffold that uses tandem beta-propeller modules to self-associate and organize spindle microtubules. By assembling higher-order oligomers that stabilize and crosslink microtubule arrays, it supports chromosome alignment at the metaphase plate and fine-tunes mitotic spindle assembly. The same scaffold concentrates at the midbody during cytokinesis and transiently associates with nuclear-proximal structures during division, collectively coordinating microtubule-based architecture and cell-cycle transitions.","plain_language":"EML3 has barely been studied. The model's best guess: A soluble cytoskeletal scaffold that uses tandem beta-propeller modules to self-associate and organize spindle microtubules. By assembling higher-order oligomers that stabilize and crosslink microtubule arrays, it supports chromosome alignment at the metaphase plate and fine-tunes mitotic spindle assembly.","uniprot_summary":"Involved in spindle assembly and chromosome congression.","go_terms":{"molecular_function":[{"id":"GO:0043621","label":"protein self-association"}],"biological_process":[{"id":"GO:0007080","label":"mitotic metaphase plate congression"},{"id":"GO:1901673","label":"regulation of mitotic spindle assembly"}],"cellular_component":[{"id":"GO:0030496","label":"midbody"},{"id":"GO:0005737","label":"cytoplasm"},{"id":"GO:0005634","label":"nucleus"},{"id":"GO:1990498","label":"mitotic spindle microtubule"}]},"interpro":[{"id":"IPR011047","name":"Quinoprotein alcohol dehydrogenase-like superfamily","type":"homologous_superfamily","start":243,"end":869},{"id":"IPR015943","name":"WD40/YVTN repeat-like-containing domain superfamily","type":"homologous_superfamily","start":244,"end":868},{"id":"IPR055439","name":"EML-like, first beta-propeller domain","type":"domain","start":298,"end":583},{"id":"IPR055442","name":"EML-like, second beta-propeller domain","type":"domain","start":600,"end":869},{"id":"IPR050630","name":"WD repeat Echinoderm Microtubule-associated Protein-like","type":"family","start":14,"end":871},{"id":"IPR005108","name":"HELP motif","type":"conserved_site","start":243,"end":282},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":294,"end":343},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":394,"end":433},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":449,"end":486},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":503,"end":542},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":586,"end":625},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":669,"end":708},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":715,"end":755},{"id":"IPR001680","name":"WD40 repeat","type":"repeat","start":828,"end":869}],"reasoning":"I begin by dissecting the InterPro architecture and its order along the polypeptide. The sequence is dominated by tandem beta-propeller modules characteristic of EML proteins. A broad family signature, IPR050630 (WD repeat Echinoderm Microtubule-associated Protein-like, residues 14–871), frames the entire protein as an EML-class scaffold. Within this scaffold, two discrete propeller assemblies are evident: IPR055439 (EML-like, first beta-propeller domain, residues 298–583) followed by IPR055442 (EML-like, second beta-propeller domain, residues 600–869). These are supported by multiple WD40 repeat calls—IPR001680 (WD40 repeat) at positions 294–343, 394–433, 449–486, 503–542, 586–625, 669–708, 715–755, and 828–869—which collectively define the blades that fold into two beta-propeller platforms. The N-terminal region preceding the first propeller harbors IPR005108 (HELP motif, residues 243–282), a hallmark of EML proteins that nucleates higher-order self-assembly and microtubule association. Two superfamily-level annotations reinforce this fold: IPR011047 (Quinoprotein alcohol dehydrogenase-like superfamily, residues 243–869) and IPR015943 (WD40/YVTN repeat-like-containing domain superfamily, residues 244–868), both pointing to a propeller-based architecture rather than enzymatic chemistry. The ordered layout—HELP motif leading into tandem WD40-based propellers—creates a rigid yet adaptable scaffold optimized for multivalent binding and polymer association.\n\nThis architecture dictates the molecular function. Tandem WD40 beta-propellers and the HELP motif together drive oligomerization and lattice engagement; such assemblies frequently polymerize or oligomerize to form higher-order structures. This causally supports GO:0043621 protein self-association as the primary molecular function: the HELP motif seeds self-association, while the paired propellers stabilize higher-order assemblies and provide avidity for cytoskeletal targets.\n\nFrom this molecular function, the biological processes follow. Beta-propeller scaffolds that self-associate are well-suited to regulate microtubule arrays that define spindle architecture. By stabilizing and organizing spindle microtubules, the protein directly contributes to GO:0007080 mitotic metaphase plate congression, ensuring chromosomes align properly. The same scaffolded assemblies modulate the fidelity and timing of spindle formation, aligning with GO:1901673 regulation of mitotic spindle assembly. The propeller-based platform can tune microtubule nucleation and crosslinking, thereby governing spindle geometry and dynamics.\n\nCellular localization emerges naturally from these roles. The absence of transmembrane segments and the presence of soluble beta-propeller modules indicate a cytosolic protein, consistent with GO:0005737 cytoplasm. Its operational site during division is the mitotic apparatus: GO:1990498 mitotic spindle microtubule is the immediate structural niche where the scaffold exerts control. As mitosis concludes, the same self-associating scaffold is poised to concentrate at the cytokinetic bridge, supporting GO:0030496 midbody. Transient nuclear proximity during cell-cycle transitions explains detection in GO:0005634 nucleus, likely reflecting shuttling or perinuclear assembly rather than stable chromatin binding.\n\nMechanistically, the HELP motif initiates oligomerization that builds a multivalent, two-propeller platform. This platform binds and crosslinks spindle microtubules, stabilizes kinetochore-proximal arrays, and concentrates at the midbody during cytokinesis. I hypothesize that it forms higher-order oligomers that template microtubule bundles and recruit spindle assembly factors. Likely partners include tubulin heterodimers and microtubule-associated proteins that regulate spindle assembly and congression. At the midbody, it may transiently engage centralspindlin and midbody scaffolds to coordinate abscission. Together, these interactions allow the scaffold to choreograph spindle assembly, chromosome alignment, and late-cytokinetic architecture through self-association and beta-propeller-mediated binding.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q32P44.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q32P44"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q32P44/entry","atlas":"/p/Q32P44"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}