ZFYVE26 encodes spastizin/SPG15, a FYVE-domain PI3P-binding protein that functions with SPG11/spatacsin and AP-5 in endolysosomal membrane remodeling. The strongest protein-homeostasis evidence supports a core role in autophagic lysosome reformation, lysosomal membrane organization, membrane bending, and autophagosome maturation through PI3P-dependent recruitment to lysosomal/late-endosomal membranes. ZFYVE26 also has experimentally supported cytokinesis and HR-DSBR roles, but its principal cellular role is endolysosomal membrane remodeling.
Definition: A lysosome organization process in which autolysosomal membranes tubulate and regenerate functional lysosomes after autophagic degradation.
Justification: ZFYVE26/spastizin and SPG11/spatacsin are described as pivotal for ALR and essential for initiation of lysosomal tubulation, but the review must currently use broader lysosome organization and lysosomal membrane organization terms.
Parent term: lysosome organization
Supporting Evidence:
Definition: A lysosomal membrane organization process in which the AP5-SPG11-SPG15 complex binds PI3P-positive membranes, senses curvature, and remodels membranes during autolysosome tubulation.
Justification: The 2025 structural study supports PI3P binding, curvature sensing, and membrane remodeling by the AP5-SPG11-SPG15 complex, but current GO terms separate membrane bending from the specific lysosomal complex/process context.
Parent term: lysosomal membrane organization
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005813 centrosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Centrosome localization is supported in the FYVE-CENT cytokinesis paper, but it reflects the non-core cytokinesis role rather than the endolysosomal proteostasis core. Reason: Retain as non-core localization tied to the midbody/cytokinesis context. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0030496 midbody | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Midbody localization is directly supported and mechanistically linked to PI3P-dependent cytokinesis, but it is non-core for this proteostasis-focused review. Reason: Retain as non-core localization tied to cytokinesis. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: ZFYVE26/spastizin has an informative FYVE-domain molecular function: PI3P binding. This binding recruits spastizin to PI3P-positive membranes in cytokinesis and is also required for lysosomal targeting/AP5-SPG11-SPG15 membrane remodeling. Reason: Retain PI3P binding as the core molecular function that links spastizin to both midbody biology and the proteostasis-relevant endolysosomal membrane-remodeling machinery. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0032465 regulation of cytokinesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ZFYVE26/FYVE-CENT has direct midbody/cytokinesis evidence, but this is not the core proteostasis function emphasized by the PN review. Reason: Retain as a supported non-core cytokinesis role while prioritizing ALR/endolysosomal membrane organization as the proteostasis core. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0000281 mitotic cytokinesis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Mitotic cytokinesis is supported by the FYVE-CENT midbody paper, but it is a non-core role relative to ZFYVE26/spastizin proteostasis biology. Reason: Retain as non-core cytokinesis biology. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0000724 double-strand break repair via homologous recombination | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: SPG15/ZFYVE26 silencing affected the DR-GFP homologous recombination readout in the KIAA0415/SPG48 DNA-repair study, but this is not the principal proteostasis function. Reason: Retain as non-core experimental DNA-repair context with the caveat that the better-supported core is endolysosomal membrane remodeling. Supporting Evidence: PMID:20613862 KIAA0415 interacts with SPG11, SPG15 PMID:20613862 significant reduction of GFP positive cells were observed upon silencing of C20orf29 and SPG15 |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Centrosome localization is supported in the FYVE-CENT cytokinesis paper, but it reflects the non-core cytokinesis role rather than the endolysosomal proteostasis core. Reason: Retain as non-core localization tied to the midbody/cytokinesis context. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0007040 lysosome organization | IEA GO_REF:0000117 | ACCEPT | Summary: Lysosome organization is the best current GO representation for spastizin-dependent ALR, free lysosome regeneration, lysosomal tubulation, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core proteostasis function; GO lacks a more specific autophagic lysosome reformation term in the review file. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:37871017 Spastizin and AP5Z1 contribute to regulate tubular lysosome formation PMID:37871017 indirectly regulates spastizin recruitment at lysosomes |
| GO:0030496 midbody | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Midbody localization is directly supported and mechanistically linked to PI3P-dependent cytokinesis, but it is non-core for this proteostasis-focused review. Reason: Retain as non-core localization tied to cytokinesis. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: ZFYVE26/spastizin has an informative FYVE-domain molecular function: PI3P binding. This binding recruits spastizin to PI3P-positive membranes in cytokinesis and is also required for lysosomal targeting/AP5-SPG11-SPG15 membrane remodeling. Reason: Retain PI3P binding as the core molecular function that links spastizin to both midbody biology and the proteostasis-relevant endolysosomal membrane-remodeling machinery. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: The FYVE zinc finger implies structural metal binding, but this annotation is less informative than the experimentally supported PI3P-binding function. Reason: Use PI3P binding as the informative molecular-function term for the FYVE domain rather than retaining generic metal ion binding as a core function. Proposed replacements: phosphatidylinositol-3-phosphate binding Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0005515 protein binding | IPI PMID:23825025 Interaction between AP-5 and the hereditary spastic parapleg... | MODIFY | Summary: The AP-5/SPG11/SPG15 interaction is real, but generic protein binding obscures the coat-like endolysosomal membrane-organization role. Reason: Replace generic binding with lysosomal membrane organization and lysosome organization for the AP5-SPG11-SPG15 coat context. Proposed replacements: lysosomal membrane organization lysosome organization Supporting Evidence: PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0005515 protein binding | IPI PMID:37871017 Spatacsin regulates directionality of lysosome trafficking b... | MODIFY | Summary: The spastizin/AP5Z1/motor-protein interaction context is biologically meaningful, but the informative function is tubular lysosome formation and lysosome trafficking organization rather than generic protein binding. Reason: Replace generic binding with lysosome organization/lysosomal membrane organization. Proposed replacements: lysosome organization lysosomal membrane organization Supporting Evidence: PMID:37871017 Spastizin and AP5Z1 contribute to regulate tubular lysosome formation PMID:37871017 indirectly regulates spastizin recruitment at lysosomes file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0005515 protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: The 2025 structural paper supports a membrane-remodeling AP5-SPG11-SPG15 complex, not generic protein binding as an informative molecular function. Reason: Replace generic binding with membrane bending, lysosomal membrane organization, and lysosome organization. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0042802 identical protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: Identical protein binding is less informative than the structural mechanism showing SPG11-SPG15/AP5 assembly driving PI3P-dependent membrane remodeling. Reason: Replace the generic self/complex-binding term with membrane bending and lysosomal membrane organization. Proposed replacements: membrane bending lysosomal membrane organization Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0005764 lysosome | IPI PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome is a core compartment for ZFYVE26/spastizin because ALR and AP5-SPG11-SPG15 membrane remodeling depend on spastizin recruitment to lysosomal/endolysosomal membranes. Reason: Retain as a core endolysosomal location. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0005770 late endosome | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP-5/SPG11/SPG15 colocalization and the 2025 AP5-SPG11-SPG15 late-endosome membrane sorting/remodeling model. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 machinery. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0097212 lysosomal membrane organization | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosomal membrane organization is directly supported by the AP5-SPG11-SPG15 PI3P-dependent membrane-remodeling study and ALR/tubulation evidence. Reason: Retain as a core proteostasis process. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0097753 membrane bending | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Membrane bending is supported by the AP5-SPG11-SPG15 structural study; the lysosomal/endolysosomal context should remain explicit in curation notes. Reason: Retain as a core membrane-remodeling process coupled to lysosomal membrane organization. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation |
| GO:0005764 lysosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosome is a core compartment for ZFYVE26/spastizin because ALR and AP5-SPG11-SPG15 membrane remodeling depend on spastizin recruitment to lysosomal/endolysosomal membranes. Reason: Retain as a core endolysosomal location. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0005770 late endosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP-5/SPG11/SPG15 colocalization and the 2025 AP5-SPG11-SPG15 late-endosome membrane sorting/remodeling model. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 machinery. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0007040 lysosome organization | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosome organization is the best current GO representation for spastizin-dependent ALR, free lysosome regeneration, lysosomal tubulation, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core proteostasis function; GO lacks a more specific autophagic lysosome reformation term in the review file. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:37871017 Spastizin and AP5Z1 contribute to regulate tubular lysosome formation PMID:37871017 indirectly regulates spastizin recruitment at lysosomes |
| GO:0005764 lysosome | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome is a core compartment for ZFYVE26/spastizin because ALR and AP5-SPG11-SPG15 membrane remodeling depend on spastizin recruitment to lysosomal/endolysosomal membranes. Reason: Retain as a core endolysosomal location. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0005769 early endosome | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | KEEP AS NON CORE | Summary: The cached PMID:25365221 abstract does not verify the early-endosome row, but independent spastizin literature reports partial early-endosome colocalization. Reason: Retain as a non-core reported compartment rather than a defining proteostasis location. Supporting Evidence: PMID:24030950 co-localizes partially with early endosomes, the endoplasmic reticulum, microtubules and vesicles involved in protein trafficking file:human/ZFYVE26/ZFYVE26-notes.md The seeded paper's accessible abstract does not verify early endosome, but independent Brain abstract reports partial early-endosome colocalization. |
| GO:0005770 late endosome | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Late endosome is supported by AP-5/SPG11/SPG15 colocalization and the 2025 AP5-SPG11-SPG15 late-endosome membrane sorting/remodeling model. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 machinery. Supporting Evidence: PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0007040 lysosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation for spastizin-dependent ALR, free lysosome regeneration, lysosomal tubulation, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core proteostasis function; GO lacks a more specific autophagic lysosome reformation term in the review file. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:37871017 Spastizin and AP5Z1 contribute to regulate tubular lysosome formation PMID:37871017 indirectly regulates spastizin recruitment at lysosomes |
| GO:0019901 protein kinase binding | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | UNDECIDED | Summary: The available cached PMID:25365221 text supports ALR, PI3P-dependent lysosomal targeting, and lysosomal tubulation, but it does not provide enough evidence to verify protein kinase binding for ZFYVE26. Reason: Leave undecided pending access to the underlying full-text/MGI evidence for this specific molecular-function annotation. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation file:human/ZFYVE26/ZFYVE26-notes.md The `GO:0019901 protein kinase binding` annotation from PMID:25365221 could not be verified from the cached abstract. |
| GO:1905037 autophagosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR paper primarily supports lysosome reformation/tubulation after autophagy rather than organization of autophagosomes themselves. Reason: Replace with lysosome organization for the PMID:25365221 ALR evidence. Add autophagosome maturation separately from PMID:24030950, which directly supports that term. Proposed replacements: lysosome organization autophagosome maturation Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:24030950 spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation PMID:24030950 impairment of autophagosome maturation and an accumulation of immature autophagosomes |
| GO:0007040 lysosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation for spastizin-dependent ALR, free lysosome regeneration, lysosomal tubulation, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core proteostasis function; GO lacks a more specific autophagic lysosome reformation term in the review file. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:37871017 Spastizin and AP5Z1 contribute to regulate tubular lysosome formation PMID:37871017 indirectly regulates spastizin recruitment at lysosomes |
| GO:1905037 autophagosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR paper primarily supports lysosome reformation/tubulation after autophagy rather than organization of autophagosomes themselves. Reason: Replace with lysosome organization for the PMID:25365221 ALR evidence. Add autophagosome maturation separately from PMID:24030950, which directly supports that term. Proposed replacements: lysosome organization autophagosome maturation Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:24030950 spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation PMID:24030950 impairment of autophagosome maturation and an accumulation of immature autophagosomes |
| GO:0032465 regulation of cytokinesis | IMP PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr... | KEEP AS NON CORE | Summary: ZFYVE26/FYVE-CENT has direct midbody/cytokinesis evidence, but this is not the core proteostasis function emphasized by the PN review. Reason: Retain as a supported non-core cytokinesis role while prioritizing ALR/endolysosomal membrane organization as the proteostasis core. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: Lysosomal membrane association is supported by lysosomal membrane proteomics and is consistent with the AP5-SPG11-SPG15 lysosomal membrane remodeling model. Reason: Retain as a broad core endolysosomal membrane location. Supporting Evidence: PMID:17897319 identified 58 proteins, known to reside at least partially in the lysosomal membrane PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:20613862 A genome-scale DNA repair RNAi screen identifies SPG48 as a ... | KEEP AS NON CORE | Summary: SPG15/ZFYVE26 silencing affected the DR-GFP homologous recombination readout in the KIAA0415/SPG48 DNA-repair study, but this is not the principal proteostasis function. Reason: Retain as non-core experimental DNA-repair context with the caveat that the better-supported core is endolysosomal membrane remodeling. Supporting Evidence: PMID:20613862 KIAA0415 interacts with SPG11, SPG15 PMID:20613862 significant reduction of GFP positive cells were observed upon silencing of C20orf29 and SPG15 |
| GO:0005515 protein binding | IPI PMID:20613862 A genome-scale DNA repair RNAi screen identifies SPG48 as a ... | MARK AS OVER ANNOTATED | Summary: The SPG15 interaction evidence supports membership in an HSP/DNA-repair-associated complex, but generic protein binding is not useful as a retained molecular function. Reason: Do not retain generic protein binding; the same paper already supports a non-core HR-DSBR process annotation. Supporting Evidence: PMID:20613862 KIAA0415 interacts with SPG11, SPG15 PMID:20613862 significant reduction of GFP positive cells were observed upon silencing of C20orf29 and SPG15 file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0005515 protein binding | IPI PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr... | MODIFY | Summary: The KIF13A/TTC19/FYVE-CENT interactions support recruitment of cytokinesis machinery to the PI3P-positive midbody rather than generic protein binding as a useful function. Reason: Replace generic binding with regulation of cytokinesis for this evidence source. Proposed replacements: regulation of cytokinesis Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells file:human/ZFYVE26/ZFYVE26-notes.md generic `protein binding` rows should be replaced by lysosome organization, lysosomal membrane organization, membrane bending, or regulation of cytokinesis depending on the source |
| GO:0005813 centrosome | IDA PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr... | KEEP AS NON CORE | Summary: Centrosome localization is supported in the FYVE-CENT cytokinesis paper, but it reflects the non-core cytokinesis role rather than the endolysosomal proteostasis core. Reason: Retain as non-core localization tied to the midbody/cytokinesis context. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0030496 midbody | IDA PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr... | KEEP AS NON CORE | Summary: Midbody localization is directly supported and mechanistically linked to PI3P-dependent cytokinesis, but it is non-core for this proteostasis-focused review. Reason: Retain as non-core localization tied to cytokinesis. Supporting Evidence: PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IDA PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr... | ACCEPT | Summary: ZFYVE26/spastizin has an informative FYVE-domain molecular function: PI3P binding. This binding recruits spastizin to PI3P-positive membranes in cytokinesis and is also required for lysosomal targeting/AP5-SPG11-SPG15 membrane remodeling. Reason: Retain PI3P binding as the core molecular function that links spastizin to both midbody biology and the proteostasis-relevant endolysosomal membrane-remodeling machinery. Supporting Evidence: PMID:25365221 pivotal for autophagic lysosome reformation (ALR) PMID:25365221 Lysosomal targeting of spastizin required an intact FYVE domain, which binds phosphatidylinositol 3-phosphate PMID:25365221 Loss of spastizin or spatacsin resulted in depletion of free lysosomes PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:40175557 essential for the initiation of autolysosome tubulation PMID:23825025 the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15 PMID:23825025 AP-5, SPG11, and SPG15 colocalize on a late endosomal/lysosomal compartment PMID:23825025 SPG15 facilitating the docking of the coat onto membranes by interacting with PI3P via its FYVE domain PMID:20208530 PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26) PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to the midbody requires another FYVE-CENT-interacting protein, the microtubule motor KIF13A PMID:20208530 cytokinesis arrest and an increased number of binucleate and multinucleate cells |
| GO:0097352 autophagosome maturation | IMP PMID:24030950 Defective autophagy in spastizin mutated patients with hered... | NEW | Summary: Spastizin has direct autophagosome-maturation evidence through patient-cell and silencing experiments showing impaired maturation and immature autophagosome accumulation when spastizin is absent or mutant. Reason: Add autophagosome maturation as a distinct annotation from the ALR/lysosome-organization rows, because PMID:24030950 explicitly supports maturation of autophagosomes. Supporting Evidence: PMID:24030950 spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation PMID:24030950 impairment of autophagosome maturation and an accumulation of immature autophagosomes |
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Download this section (compressed HTML)Q: Should GO add an autophagic lysosome reformation term under lysosome organization so ZFYVE26/SPG15, SPG11, PIP5K1B, KIF5B, and related ALR factors can be annotated without overusing broad lysosome organization?
Suggested experts: Li Yu, Craig Blackstone, GO biological process editors
Q: Should spastizin-mediated autophagosome maturation through Beclin 1-UVRAG-Rubicon be curated separately from AP5-SPG11-SPG15-dependent ALR/lysosomal membrane remodeling?
Suggested experts: Maria Teresa Bassi, Li Yu, GO autophagy editors
Q: Should the HR-DSBR annotation for ZFYVE26/SPG15 remain as a non-core process, or is the DR-GFP evidence too indirect relative to the stronger SPG48/KIAA0415 focus of PMID:20613862?
Suggested experts: Andreas Ladurner, Craig Blackstone, GO DNA repair editors
Experiment: Rescue ZFYVE26/SPG15-deficient cells with FYVE-domain and AP5/SPG11-interface mutants, then quantify starvation-refeeding ALR, free lysosome regeneration, lysosomal tubulation, and autophagosome maturation.
Hypothesis: PI3P binding and AP5-SPG11-SPG15 complex assembly are required for spastizin-dependent ALR and lysosomal membrane organization.
Type: genetic rescue/live-cell lysosome and autophagy imaging
Experiment: Measure membrane curvature sensing and remodeling by purified AP5-SPG11-SPG15 complexes containing SPG15 FYVE-domain or complex-interface mutants on PI3P-containing liposomes.
Hypothesis: Spastizin contributes directly to PI3P-dependent membrane remodeling as part of the AP5-SPG11-SPG15 complex.
Type: in vitro membrane remodeling/structural biochemistry
Experiment: Separate cytokinesis, autophagosome maturation, and ALR outputs using domain-specific ZFYVE26 mutants in matched midbody, Beclin 1-UVRAG-Rubicon, and lysosomal tubulation assays.
Hypothesis: ZFYVE26 has separable PI3P-dependent cytokinesis and proteostasis functions that should not be collapsed into one broad GO process.
Type: domain-function epistasis
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