{"uniprot":"Q9BYX7","gene":"POTEKP","name":"Putative beta-actin-like protein 3","organism":"Homo sapiens (Human)","status":"dark","length":375,"sequence":"MDDDTAVLVIDNGSGMCKAGFAGDDAPQAVFPSIVGRPRHQGMMEGMHQKESYVGKEAQSKRGMLTLKYPMEHGIITNWDDMEKIWHHTFYNELRVAPEEHPILLTEAPLNPKANREKMTQIMFETFNTPAMYVAIQAVLSLYTSGRTTGIVMDSGDGFTHTVPIYEGNALPHATLRLDLAGRELTDYLMKILTERGYRFTTTAEQEIVRDIKEKLCYVALDSEQEMAMAASSSSVEKSYELPDGQVITIGNERFRCPEALFQPCFLGMESCGIHKTTFNSIVKSDVDIRKDLYTNTVLSGGTTMYPGIAHRMQKEITALAPSIMKIKIIAPPKRKYSVWVGGSILASLSTFQQMWISKQEYDESGPSIVHRKCF","function_summary":"A cytosolic actin that assembles into dynamic filaments and uses an ATP-driven conformational cycle to regulate cytoskeletal organization. By tuning filament nucleation, elongation, and turnover, it scaffolds adhesion and junctional complexes that govern cell adhesion, migration, and epithelial and vascular morphogenesis. Its soluble pool in the cytoplasm supports stress fiber and focal adhesion dynamics and contributes to specialized programs such as platelet aggregation, angiogenesis, and ocular homeostasis, with additional trafficking into extracellular vesicles.","plain_language":"POTEKP has barely been studied. The model's best guess: A cytosolic actin that assembles into dynamic filaments and uses an ATP-driven conformational cycle to regulate cytoskeletal organization. By tuning filament nucleation, elongation, and turnover, it scaffolds adhesion and junctional complexes that govern cell adhesion, migration, and epithelial and vascular morphogenesis.","uniprot_summary":"Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007155","label":"cell adhesion"},{"id":"GO:0030168","label":"platelet activation"},{"id":"GO:0001525","label":"angiogenesis"},{"id":"GO:0034109","label":"homotypic cell-cell adhesion"},{"id":"GO:0070527","label":"platelet aggregation"},{"id":"GO:0032956","label":"regulation of actin cytoskeleton organization"},{"id":"GO:0010628","label":"positive regulation of gene expression"},{"id":"GO:0001895","label":"retina homeostasis"},{"id":"GO:0030335","label":"positive regulation of cell migration"},{"id":"GO:0008104","label":"protein localization"},{"id":"GO:0001944","label":"tissue homeostasis"},{"id":"GO:0001738","label":"morphogenesis of a polarized epithelium"},{"id":"GO:0051492","label":"regulation of stress fiber assembly"},{"id":"GO:0030335","label":"positive regulation of cell migration"},{"id":"GO:0008104","label":"protein localization"},{"id":"GO:0150105","label":"protein localization to cell-cell junction"},{"id":"GO:0051893","label":"regulation of focal adhesion assembly"},{"id":"GO:0120193","label":"tight junction organization"},{"id":"GO:0120192","label":"tight junction assembly"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"},{"id":"GO:0070062","label":"extracellular exosome"}]},"interpro":[{"id":"IPR043129","name":"ATPase, nucleotide binding domain","type":"homologous_superfamily","start":3,"end":152},{"id":"IPR043129","name":"ATPase, nucleotide binding domain","type":"homologous_superfamily","start":146,"end":375},{"id":"IPR004000","name":"Actin family","type":"family","start":3,"end":375},{"id":"IPR020902","name":"Actin/actin-like conserved site","type":"conserved_site","start":104,"end":116},{"id":"IPR004001","name":"Actin, conserved site","type":"conserved_site","start":356,"end":364}],"reasoning":"I begin with the InterPro architecture. The sequence is dominated by IPR004000 (Actin family, residues 3–375), establishing a canonical actin fold composed of two lobes that cradle a nucleotide. Two overlapping ATPase/nucleotide-binding superfamily signatures—IPR043129 (ATPase, nucleotide binding domain, residues 3–152) in the N-terminal lobe and IPR043129 (ATPase, nucleotide binding domain, residues 146–375) in the C-terminal lobe—define the bilobal P-loop–like architecture that binds and hydrolyzes ATP. The presence of IPR020902 (Actin/actin-like conserved site, residues 104–116) and IPR004001 (Actin, conserved site, residues 356–364) marks catalytic and structural hotspots that coordinate Mg2+-ATP and transmit conformational changes between lobes. This ordered layout—nucleotide-binding cores bracketed by actin-specific conserved sites—causes ATP-dependent conformational switching and polymerization behavior that is characteristic of cytoskeletal actins.\n\nFrom this architecture, the molecular function resolves as a multivalent scaffold that binds other proteins through filament assembly and surface grooves, aligning with GO:0005515 protein binding. The actin fold’s ATPase cycle regulates filament assembly and disassembly; this dynamic assembly underlies broad cellular processes. By controlling filament turnover and higher-order structures, the protein drives GO:0032956 regulation of actin cytoskeleton organization and GO:0051492 regulation of stress fiber assembly. Through coupling to adhesion complexes, it modulates GO:0051893 regulation of focal adhesion assembly and supports GO:0007155 cell adhesion and GO:0034109 homotypic cell-cell adhesion. Its role in junctional complexes extends to GO:0120192 tight junction assembly and GO:0150105 protein localization to cell-cell junction.\n\nActin-driven remodeling also powers cell movement and tissue morphogenesis. Filament assembly and turnover promote GO:0030335 positive regulation of cell migration and contribute to GO:0001525 angiogenesis and GO:0001738 morphogenesis of a polarized epithelium. In specialized contexts, actin dynamics support GO:0001895 retina homeostasis and GO:0070527 platelet aggregation, reflecting actin’s central role in hemostatic and ocular tissues. Actin’s influence on transcriptional and trafficking hubs explains GO:0010628 positive regulation of gene expression and GO:0008104 protein localization.\n\nCellular localization follows from solubility and assembly behavior. The absence of transmembrane segments and the soluble actin fold place the protein in the cytoplasm and specifically the GO:0005829 cytosol, where monomers polymerize into cytoplasmic filaments. Actin’s presence in extracellular vesicles and its trafficking through endomembrane pathways rationalize detection in GO:0070062 extracellular exosome.\n\nMechanistically, ATP binding and hydrolysis within the actin bilobal core drive transitions between G- and F-actin states. This nucleotide-coupled cycle tunes filament nucleation, elongation, and severing, thereby orchestrating adhesion complexes, stress fibers, and junctional assemblies. I hypothesize that the protein forms transient assemblies with actin-binding and nucleation factors—such as nucleators and monomer carriers—to channel filament growth toward adhesion and junction sites. Likely partners include nucleation-promoting factors and capping/severing modulators that localize actin remodeling to cell junctions and focal adhesions, thereby coupling cytoskeletal dynamics to adhesion, migration, and tissue-specific programs.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9BYX7.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9BYX7"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9BYX7/entry","atlas":"/p/Q9BYX7"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}