{"uniprot":"P59074","gene":"CHMP4BP1","name":"Putative charged multivesicular body protein 4B-like protein CHMP4BP1","organism":"Homo sapiens (Human)","status":"dark","length":171,"sequence":"MLSKKQEFLEKKIEQRHGTKNKPAALQALKRKKRYEKQLAQIDGTLSTIEFQQQALENANTNTEVLKNMGSAAKAKKAAHDNMDIDKVDELMQDIADQQELGEEISTAISKPVGFGEKSDEDELMAELEELEQEEPDKNLLEVSGPETVPLPNVPSIALPSKPAKKRKTTT","function_summary":"A cytosolic ESCRT-III filament-forming factor that homodimerizes and polymerizes to remodel membranes during endosomal sorting, multivesicular body biogenesis, and late cytokinesis. By assembling dynamic scaffolds at late endosomes and the midbody ring, it drives intraluminal vesicle formation, coordinates abscission, and couples membrane fission to ubiquitin-dependent cargo degradation and autophagic maturation. Its membrane-remodeling capacity extends to plasma membrane repair and enveloped-virus budding, and pathway tuning in neural and proliferative contexts helps restrain excessive autophagy and supports cell survival.","plain_language":"CHMP4BP1 has barely been studied. The model's best guess: A cytosolic ESCRT-III filament-forming factor that homodimerizes and polymerizes to remodel membranes during endosomal sorting, multivesicular body biogenesis, and late cytokinesis. By assembling dynamic scaffolds at late endosomes and the midbody ring, it drives intraluminal vesicle formation, coordinates abscission, and couples membrane fission to ubiquitin-dependent cargo degradation and autophagic maturation.","uniprot_summary":"Probable peripherally associated component of the endosomal sorting complex required for transport III (ESCRT-III) complex, a cytosolic complex that is recruited to endosomal or plasma-membrane-derived invaginations to drive membrane scission. The ESCRT-III complex is required for the down-regulation and internalization of membrane proteins, for the formation of multivesicular bodies (MVBs) and cytokinesis (By similarity).","go_terms":{"molecular_function":[{"id":"GO:0042803","label":"protein homodimerization activity"}],"biological_process":[{"id":"GO:0019068","label":"virion assembly"},{"id":"GO:0046761","label":"viral budding from plasma membrane"},{"id":"GO:0046755","label":"viral budding from plasma membrane"},{"id":"GO:0039702","label":"viral budding via host ESCRT complex"},{"id":"GO:0051301","label":"cell division"},{"id":"GO:0061952","label":"midbody abscission"},{"id":"GO:0046907","label":"intracellular transport"},{"id":"GO:0061640","label":"cytoskeleton-dependent cytokinesis"},{"id":"GO:0007080","label":"mitotic metaphase plate congression"},{"id":"GO:0010507","label":"negative regulation of autophagy"},{"id":"GO:1901564","label":"organonitrogen compound metabolic process"},{"id":"GO:1901215","label":"negative regulation of neuron death"},{"id":"GO:2000785","label":"regulation of autophagosome assembly"},{"id":"GO:0007032","label":"endosome organization"},{"id":"GO:0039702","label":"viral budding via host ESCRT complex"},{"id":"GO:0006886","label":"intracellular protein transport"},{"id":"GO:0007080","label":"mitotic metaphase plate congression"},{"id":"GO:0061640","label":"cytoskeleton-dependent cytokinesis"},{"id":"GO:0015031","label":"protein transport"},{"id":"GO:0045047","label":"protein targeting to ER"},{"id":"GO:0071985","label":"multivesicular body sorting pathway"},{"id":"GO:0016242","label":"negative regulation of macroautophagy"},{"id":"GO:0007041","label":"lysosomal transport"},{"id":"GO:0090169","label":"regulation of spindle assembly"},{"id":"GO:0001778","label":"plasma membrane repair"},{"id":"GO:0097352","label":"autophagosome maturation"},{"id":"GO:0061952","label":"midbody abscission"},{"id":"GO:0036258","label":"multivesicular body assembly"},{"id":"GO:1901673","label":"regulation of mitotic spindle assembly"},{"id":"GO:0051603","label":"proteolysis involved in protein catabolic process"},{"id":"GO:0065003","label":"protein-containing complex assembly"},{"id":"GO:0061952","label":"midbody abscission"},{"id":"GO:0031468","label":"nuclear membrane reassembly"},{"id":"GO:1902774","label":"late endosome to lysosome transport"},{"id":"GO:0051258","label":"protein polymerization"},{"id":"GO:0097320","label":"plasma membrane tubulation"},{"id":"GO:0006620","label":"post-translational protein targeting to endoplasmic reticulum membrane"},{"id":"GO:0043162","label":"ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway"}],"cellular_component":[{"id":"GO:0005829","label":"cytosol"}]},"interpro":[{"id":"IPR005024","name":"Vacuolar-sorting protein SNF7-like","type":"family","start":1,"end":165}],"reasoning":"I begin with the InterPro architecture: a single, continuous SNF7-like ESCRT-III family signature, IPR005024 (Vacuolar-sorting protein SNF7-like, residues 1–165), spans essentially the entire polypeptide. This architecture encodes a helical hairpin core that self-assembles into curved polymers on membranes. Such ESCRT-III family modules nucleate and extend filamentous scaffolds that remodel membranes by constriction and fission. Their N-to-C terminal continuity and propensity to form higher-order assemblies causally impose homotypic interfaces that drive GO:0042803 protein homodimerization activity as a primary molecular function.\n\nHomodimerization by the SNF7-like core seeds filament formation that underlies multiple membrane-remodeling pathways. ESCRT-III polymers generate and stabilize narrow membrane necks, directly producing GO:0061952 midbody abscission and GO:0061640 cytoskeleton-dependent cytokinesis. By assembling and disassembling at the midbody ring, the scaffold coordinates late cytokinesis and thereby influences GO:0007080 mitotic metaphase plate congression and GO:1901673 regulation of mitotic spindle assembly through spatial coupling of the abscission checkpoint to spindle dynamics. The same polymerization logic explains GO:0051603 proteolysis involved in protein catabolic process and GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway, because ESCRT-III filaments drive intraluminal vesicle formation that delivers ubiquitinated cargo to lysosomes.\n\nThe ESCRT-III system also governs endosomal maturation and retrograde flux. By assembling at late endosomes and sorting into intraluminal vesicles, the scaffold enacts GO:0071985 multivesicular body sorting pathway and GO:0036258 multivesicular body assembly, and it channels cargo toward GO:1902774 late endosome to lysosome transport. Its membrane-remodeling capacity extends to ER-associated pathways: ESCRT-III–dependent budding and membrane repair support GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane and GO:0001778 plasma membrane repair. At the cell surface, ESCRT-III–mediated scission and tubulation underpin GO:0097320 plasma membrane tubulation and GO:0046761 viral budding from plasma membrane, GO:0039702 viral budding via host ESCRT complex, and GO:0019068 virion assembly, because enveloped viruses exploit ESCRT-driven membrane fission.\n\nAutophagic and endolysosomal pathways are tightly coupled to ESCRT-III dynamics. Filament assembly and turnover modulate autophagosome–endosome interfaces, accounting for GO:0097352 autophagosome maturation and GO:2000785 regulation of autophagosome assembly, with pathway tuning that can produce GO:0016242 negative regulation of macroautophagy under specific signaling contexts. In neural cells, this restraint on autophagy and endolysosomal stress pathways contributes to GO:1901215 negative regulation of neuron death.\n\nCellular localization follows from this assembly logic. The soluble monomeric pool resides in GO:0005829 cytosol, while membrane-bound polymers concentrate at late endosomes and the midbody. The SNF7-like architecture thus explains a dynamic cytosolic–membrane distribution that is essential for endosomal and cytokinetic functions.\n\nMechanistically, I hypothesize that this protein cycles between a soluble homodimer and higher-order ESCRT-III polymers that template membrane neck constriction. It likely partners with upstream ESCRT-I/II adaptors to nucleate assembly and with the AAA+ ATPase disassembly machinery to recycle the polymer. Through these assemblies it coordinates cytokinesis, MVB biogenesis, plasma membrane repair, and viral budding. Predicted interaction partners include ESCRT-I and II adaptors that recruit the polymer, other ESCRT-III subunits that co-assemble into curvature-generating filaments, and the VPS4 ATPase that remodels and recycles the scaffold; together these interactions channel cargo toward lysosomes and ensure faithful cell division and membrane homeostasis.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-P59074.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/P59074"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/P59074/entry","atlas":"/p/P59074"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}