SPG11 encodes spatacsin, a large cytoplasmic/peripheral membrane-associated protein that functions with SPG15/spastizin and AP-5 in endolysosomal membrane remodeling. The strongest protein-homeostasis evidence supports a core role in autophagic lysosome reformation, lysosomal tubulation, lysosome membrane recycling, and ER-linked lysosome trafficking/organization. SPG11 also has supported neuronal axonal/synaptic transport contexts, but its principal described cellular role is endolysosomal membrane remodeling.
Definition: A lysosome organization process in which autolysosomal membranes tubulate and give rise to new functional lysosomes after autophagic degradation.
Justification: SPG11/spatacsin and SPG15/spastizin are described as pivotal for ALR and essential for initiation of lysosomal tubulation, but the review currently must use broader lysosome organization and lysosomal membrane organization terms.
Parent term: lysosome organization
Supporting Evidence:
Definition: A lysosome organization process that recycles lysosomal membrane components from autolysosomes or lysosome-derived carriers to regenerate functional lysosomes.
Justification: SPG11/spatacsin is required for lysosome membrane recycling and recruits dynamin for this process, but existing GO terms are broader than the specific recycling step.
Parent term: lysosomal membrane organization
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axonogenesis is plausible from orthology and disease biology, but human experimental evidence more directly supports axonal maintenance/transport defects than a core developmental axonogenesis role. Reason: Retain as non-core neuronal/developmental context rather than the proteostasis core function. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0007268 chemical synaptic transmission | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Chemical synaptic transmission is a plausible neuronal consequence of SPG11 dysfunction, but the direct evidence centers on synaptic vesicle/cargo transport defects. Reason: Retain as non-core neuronal phenotype/context. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0008088 axo-dendritic transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axo-dendritic transport is supported by impaired anterograde vesicle trafficking in SPG11-deficient neurons, but it is secondary to the endolysosomal proteostasis core. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0030424 axon | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axon localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, axon PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0030425 dendrite | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Dendrite localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, dendrite PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0045202 synapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0048489 synaptic vesicle transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Synaptic vesicle transport is supported in neuronal models, but it is a secondary neuronal consequence/context for this proteostasis review. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nucleus is reported in early localization evidence but UniProt notes that SPG11 is mainly cytoplasmic, and the proteostasis literature centers on endolysosomal remodeling. Reason: Retain as a non-core reported location rather than a defining SPG11 location. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Nucleus file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0030424 axon | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Axon localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, axon PMID:24794856 spatacsin was located in axons and dendrites |
| GO:0030425 dendrite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Dendrite localization is supported in neurons, but it reflects the neuronal disease/transport context rather than the core ALR function. Reason: Retain as non-core neuronal localization. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cell projection, dendrite PMID:24794856 spatacsin was located in axons and dendrites |
| 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 endolysosomal coat/scaffold role. Reason: Replace generic binding with lysosomal membrane organization for the AP5-SPG11-SPG15 coat-like complex 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 AP-5, SPG15, and SPG11 form a coat-like complex |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: This proteome-scale interactome evidence is too generic to define an SPG11 molecular function. Reason: Avoid retaining GO:0005515 when no SPG11-specific mechanism is curated from the evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Proteome-scale interactome rows from PMID:25416956 and PMID:33961781 are insufficiently informative for core GO curation without a mechanism specific to SPG11 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:29949766 Inhibition of Lysosome Membrane Recycling Causes Accumulatio... | MODIFY | Summary: The dynamin interaction is mechanistic, but the informative function is lysosome membrane recycling/lysosome organization. Reason: Replace generic protein binding with lysosome organization/lysosomal membrane organization. Proposed replacements: lysosome organization lysosomal membrane organization Supporting Evidence: PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: This proteome-scale interactome evidence is too generic to define an SPG11 molecular function. Reason: Avoid retaining GO:0005515 when no SPG11-specific mechanism is curated from the evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Proteome-scale interactome rows from PMID:25416956 and PMID:33961781 are insufficiently informative for core GO curation without a mechanism specific to SPG11 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:36096339 Cytosolic sequestration of spatacsin by Protein Kinase A and... | MARK AS OVER ANNOTATED | Summary: PKA/14-3-3-dependent interaction regulates spatacsin trafficking, but generic protein binding is not an informative GO function for SPG11. Reason: Do not retain generic protein binding as a core molecular function; capture this as regulatory context in notes/questions instead. Supporting Evidence: PMID:36096339 identified a subset of 14-3-3 proteins as physiological interactors of spatacsin PMID:36096339 The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
| GO:0005515 protein binding | IPI PMID:37871017 Spatacsin regulates directionality of lysosome trafficking b... | MODIFY | Summary: The AP5Z1/spastizin interaction/regulation evidence is real, but the useful function is ER-linked tubular lysosome formation and lysosome trafficking directionality. Reason: Replace generic binding with lysosome organization, which better captures the functional outcome. Proposed replacements: lysosome organization Supporting Evidence: PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005515 protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: The structural paper defines AP5-SPG11-SPG15 assembly and membrane remodeling, not a useful standalone generic protein-binding function. Reason: Replace generic binding with membrane bending and lysosomal membrane organization. Proposed replacements: membrane bending lysosomal membrane organization Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0042802 identical protein binding | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | MODIFY | Summary: The homomeric/complex assembly evidence is less informative than the demonstrated AP5-SPG11-SPG15 membrane remodeling function. Reason: Replace identical protein binding with membrane bending and lysosomal membrane organization. Proposed replacements: membrane bending lysosomal membrane organization Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Endoplasmic reticulum is supported by recent endogenous localization and functional lysosome-trafficking evidence. Reason: Retain ER as a core functional location for SPG11-dependent tubular lysosome formation and ER-lysosome trafficking regulation. ORGANELLES check (2026-11-06) - this Ensembl projection comes from the mouse Spg11 (Q3UHA3) is_active_in IDA by MGI on PMID:37871017, which was read in full. There, endogenous spatacsin from mouse brain fractionated with the ER proteins REEP5 and STIM1 and away from the cathepsin D-containing lysosomal fraction, and V5-tagged spatacsin was mainly on the Sec61beta- or REEP5-labelled ER by STED, so the organelle claim holds for a resident pool rather than biosynthetic transit (spatacsin is not secreted). The is_active_in qualifier is justified - spatacsin at the ER promotes ER-lysosome contacts and tubular lysosome formation, and ER-lysosome contacts are reduced in Spg11 knockout cells (same paper). No ER membrane row is added. Endogenous spatacsin resisted high-salt and high- or low-pH extraction like the integral ER protein STIM1, but UniProt predicts no transmembrane segment, curates the protein as mainly cytoplasmic, and the authors place the same pool either at the ER or at nondegradative late-endosome membranes; these lines disagree, so the row stays at the root. A topology assay (protease protection of ER microsomes, or mapping a membrane-embedded segment) would settle membrane insertion. Supporting Evidence: PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Nucleolus is a weak high-throughput localization relative to the stronger cytoplasmic, ER, late-endolysosomal, and neuronal-process evidence. Reason: Do not treat nucleolus as an informative SPG11 location without stronger gene-specific mechanistic evidence. Supporting Evidence: file:human/SPG11/SPG11-notes.md Nucleolus and plasma membrane HPA rows are weak |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Plasma membrane is not a defining SPG11 location; PKA/14-3-3 work mentions trafficking from plasma membrane to intracellular space, but core function is endolysosomal/ER membrane remodeling. Reason: Retain only as non-core trafficking/regulatory context. Supporting Evidence: file:human/SPG11/SPG11-notes.md Nucleolus and plasma membrane HPA rows are weak PMID:36096339 identified a subset of 14-3-3 proteins as physiological interactors of spatacsin PMID:36096339 The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955 |
| GO:0005634 nucleus | EXP PMID:17322883 Mutations in SPG11, encoding spatacsin, are a major cause of... | KEEP AS NON CORE | Summary: Nucleus is reported in early localization evidence but UniProt notes that SPG11 is mainly cytoplasmic, and the proteostasis literature centers on endolysosomal remodeling. Reason: Retain as a non-core reported location rather than a defining SPG11 location. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Nucleus file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0005764 lysosome | IPI PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome is a supported core compartment for SPG11-dependent ALR, lysosome membrane recycling, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core endolysosomal location/process context. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005770 late endosome | IPI PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP5-SPG11-SPG15 membrane sorting/remodeling evidence and AP-5/SPG11/SPG15 colocalization. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 complex. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro 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 AP-5, SPG15, and SPG11 form a coat-like complex |
| GO:0097212 lysosomal membrane organization | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosomal membrane organization directly captures SPG11-dependent AP5-SPG11-SPG15 membrane remodeling and ALR/tubulation. Reason: Retain as a core process annotation for SPG11 in the proteostasis network. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:0097753 membrane bending | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Membrane bending is directly supported by the AP5-SPG11-SPG15 structural/mechanistic study, though the lysosomal context should be retained in curation notes. Reason: Retain as a core membrane-remodeling process coupled to lysosomal membrane organization. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005764 lysosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Lysosome is a supported core compartment for SPG11-dependent ALR, lysosome membrane recycling, and AP5-SPG11-SPG15 membrane remodeling. Reason: Retain as a core endolysosomal location/process context. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0005770 late endosome | NAS PMID:40175557 Structural basis for membrane remodeling by the AP5-SPG11-SP... | ACCEPT | Summary: Late endosome is supported by AP5-SPG11-SPG15 membrane sorting/remodeling evidence and AP-5/SPG11/SPG15 colocalization. Reason: Retain as a core endolysosomal compartment for the AP5-SPG11-SPG15 complex. Supporting Evidence: PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro 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 AP-5, SPG15, and SPG11 form a coat-like complex |
| 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 of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0007040 lysosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| GO:0007040 lysosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | ACCEPT | Summary: Lysosome organization is the best current GO representation of SPG11-dependent ALR, lysosome membrane recycling, and tubular lysosome formation. Reason: Retain as a core SPG11 function in the proteostasis network. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation PMID:29949766 spatacsin, which is required for lysosome recycling PMID:29949766 spatacsin acts downstream of clathrin and recruits dynamin to allow lysosome membrane recycling and clearance of gangliosides from lysosomes PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro |
| 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 and lysosomal tubulation, but it does not provide enough evidence to verify protein kinase binding for SPG11. Reason: Leave undecided pending access to the underlying MGI/full-text evidence for this specific molecular-function annotation. Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation file:human/SPG11/SPG11-notes.md GO:1905037 autophagosome organization is less precise |
| GO:1905037 autophagosome organization | IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR evidence concerns reformation/tubulation of lysosomes after autophagy, not organization of autophagosomes themselves. Reason: Replace with lysosome organization, which better matches depletion of free lysosomes, autolysosome accumulation, and failure of ALR. Proposed replacements: lysosome organization Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:1905037 autophagosome organization | IMP PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ... | MODIFY | Summary: The cited ALR evidence concerns reformation/tubulation of lysosomes after autophagy, not organization of autophagosomes themselves. Reason: Replace with lysosome organization, which better matches depletion of free lysosomes, autolysosome accumulation, and failure of ALR. Proposed replacements: lysosome organization Supporting Evidence: PMID:25365221 the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR) PMID:25365221 spastizin and spatacsin were essential components for the initiation of lysosomal tubulation |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Cytosol is supported by UniProt/HPA-style localization and is compatible with a large cytoplasmic scaffold associated with endolysosomal membranes. Reason: Retain cytosol as a core broad location, not as a substitute for the more specific endolysosomal/ER locations. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic |
| GO:0045202 synapse | IDA PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Synapse localization is supported by neuronal/synaptosome evidence, but it is secondary to the lysosome reformation and membrane-remodeling function. Reason: Retain as non-core neuronal localization. Supporting Evidence: PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0008088 axo-dendritic transport | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Axo-dendritic transport is supported by impaired anterograde vesicle trafficking in SPG11-deficient neurons, but it is secondary to the endolysosomal proteostasis core. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0007268 chemical synaptic transmission | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Chemical synaptic transmission is a plausible neuronal consequence of SPG11 dysfunction, but the direct evidence centers on synaptic vesicle/cargo transport defects. Reason: Retain as non-core neuronal phenotype/context. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0048489 synaptic vesicle transport | IMP PMID:24794856 Dysfunction of spatacsin leads to axonal pathology in SPG11-... | KEEP AS NON CORE | Summary: Synaptic vesicle transport is supported in neuronal models, but it is a secondary neuronal consequence/context for this proteostasis review. Reason: Retain as non-core neuronal transport biology. Supporting Evidence: PMID:24794856 spatacsin was located in axons and dendrites PMID:24794856 reduction in the anterograde vesicle trafficking indicative of impaired axonal transport PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking PMID:24794856 colocalized with cytoskeletal and synaptic vesicle (SV) markers PMID:24794856 SPG11 is implicated in axonal maintenance and cargo trafficking |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: Lysosomal membrane association is supported by proteomic evidence and is consistent with SPG11-dependent lysosomal membrane remodeling/recycling. Reason: Retain as a core endolysosomal membrane location, while noting that recent work also supports ER-associated pools. Supporting Evidence: PMID:17897319 identified 58 proteins, known to reside at least partially in the lysosomal membrane PMID:40175557 SPG11-SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes PMID:40175557 AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0005737 cytoplasm | IDA PMID:21545838 Cellular distribution and subcellular localization of spatac... | ACCEPT | Summary: SPG11/spatacsin is mainly cytoplasmic and functions as a cytoplasmic/peripheral membrane-associated endolysosomal remodeling factor. Reason: Retain cytoplasm as a core broad location, while relying on ER, late endosome, lysosome, and lysosomal membrane terms for more specific context. Supporting Evidence: file:human/SPG11/SPG11-uniprot.txt Cytoplasm, cytosol file:human/SPG11/SPG11-uniprot.txt Mainly cytoplasmic PMID:37871017 spatacsin is an ER-resident protein regulating the formation of tubular lysosomes PMID:37871017 spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking |
| GO:0031410 cytoplasmic vesicle | IDA PMID:21545838 Cellular distribution and subcellular localization of spatac... | KEEP AS NON CORE | Summary: Cytoplasmic vesicle localization is supported by early antibody localization, but the informative locations are ER, late endosome, lysosome, and lysosomal membrane. Reason: Retain as non-core/broad vesicular context rather than a defining location. Supporting Evidence: PMID:21545838 diffuse punctate, cytoplasmic PMID:21545838 protein-trafficking vesicles, endoplasmic reticulum and microtubules |
| GO:0005515 protein binding | IPI PMID:20613862 A genome-scale DNA repair RNAi screen identifies SPG48 as a ... | MARK AS OVER ANNOTATED | Summary: The interaction evidence supports AP5/SPG15/SPG11 network membership, but generic protein binding is not an informative retained function. Reason: Use the later endolysosomal membrane-remodeling terms for the functional complex; do not retain generic binding as a function. Supporting Evidence: PMID:20613862 putative helicase that interacts with SPG11 and SPG15 file:human/SPG11/SPG11-uniprot.txt Interacts with AP5Z1, AP5B1, AP5S1 and ZFYVE26 file:human/SPG11/SPG11-notes.md Generic `GO:0005515 protein binding` is overused in this record. |
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Download this section (compressed HTML)Q: Should GO add an autophagic lysosome reformation term under lysosome organization so SPG11, SPG15, KIF5B, PIP5K1B, and related ALR factors can be annotated without overusing broad lysosome organization?
Suggested experts: Li Yu, Craig Blackstone, GO biological process editors
Q: Should SPG11 be annotated to a complex/scaffold molecular function, or should AP5-SPG11-SPG15 activity be represented only through biological process terms such as lysosomal membrane organization and membrane bending?
Suggested experts: Margaret Robinson, Yong Ma, GO molecular function editors
Q: What is the best GO representation for SPG11-dependent AP5Z1 degradation and control of lysosome trafficking directionality in neurons?
Suggested experts: Frederic Darios, Giovanni Stevanin, GO biological process editors
Experiment: Rescue SPG11-null cells with SPG11 mutants defective in AP-5/SPG15 binding and quantify ALR after starvation-refeeding, including autolysosome tubulation, free lysosome regeneration, and lysosome membrane recycling.
Hypothesis: AP5-SPG11-SPG15 complex assembly is required for SPG11-dependent autophagic lysosome reformation and lysosomal membrane organization.
Type: genetic rescue/live-cell lysosome imaging
Experiment: Measure membrane curvature sensing and remodeling by purified AP5-SPG11-SPG15 complexes with SPG11 interface mutants on PI3P-containing liposomes.
Hypothesis: SPG11 contributes directly to PI3P-dependent membrane remodeling as part of the AP5-SPG11-SPG15 complex.
Type: in vitro membrane remodeling/structural biochemistry
Experiment: Track lysosome movement in polarized neurons after perturbing SPG11, AP5Z1 degradation, KIF13A, and dynein/dynactin interactions while separately scoring axonal synaptic vesicle transport.
Hypothesis: SPG11-dependent ER/lysosome membrane remodeling controls lysosome trafficking directionality independently from broader synaptic vesicle transport phenotypes.
Type: neuronal live imaging/rescue epistasis
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