Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia.
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KIAA0415 depletion causes an on-target homologous-recombination phenotype.
"Stable expression of mouse KIAA0415 in the human DR-GFP cell line rendered this cell line resistant to the human esiRNAs, authenticating a role of KIAA0415 in HR-DSBR"
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AP5Z1 coassociates with AP-5 and spastic-paraplegia complex partners.
"Immunoprecipitation experiments followed by spectrometric identification of co-isolated proteins revealed interactions of KIAA0415-LAP with SPG11, SPG15, C20orf29, and DKFZp761E198"
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Nuclear and cytoplasmic electrophoretic species were observed without current isoform resolution.
"Cell fractionations showed that the shorter isoform was predominantly nuclear, whereas the longer form was found mostly in the cytoplasm"
The fifth adaptor protein complex.
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AP5Z1 depletion perturbs the CIMPR/Vps26 endosomal compartment.
"Knockdown of either KIAA0415/SPG48 or C20orf29 phenocopies μ5 and β5 knockdowns, causing both the CIMPR and Vps26 to localise to larger puncta."
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The earlier repair phenotype is robust but its direct mechanism remains unresolved.
"The DNA repair phenotype appears to be robust and on-target, because the authors were able to rescue it with RNAi-resistant KIAA0415. However, the phenotype could be indirect."
Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15.
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The four AP-5 subunits form a stable assembly with SPG11 and SPG15.
"Here we show that the four AP-5 subunits can be
coimmunoprecipitated with SPG11 and SPG15, both from cytosol and from
detergent-extracted membranes, with a stoichiometry of ∼1:1:1:1:1:1."
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Structural basis for membrane remodeling by the AP5-SPG11-SPG15 complex.
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The N-terminal SPG11 region contacts the AP-5 assembly.
"the N-terminal
region of SPG11 is required for AP5 complex interaction and assembly."
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The assembled AP5–SPG11–SPG15 machinery remodels membranes in vitro.
"Our findings reveal that the
AP5-SPG11-SPG15 complex can bind PI3P molecules, sense membrane curvature and
drive membrane remodeling in vitro."
Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease.
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Human control-cell AP5Z1 puncta overlap LAMP1.
"Note that in control cells there is a significant overlap between LAMP1 and AP-5 ζ."
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AP5Z1 depletion causes abnormal endolysosomal storage structures.
"Note that the loss of AP-5 ζ led to the accumulation of enlarged morphologically defined endosomal structures filled with aberrant storage material, typically containing bands of striated material, multiple exaggerated membrane whorls and many intraluminal vesicles."
Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval.
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Native SPG15 complexes contain AP5Z1 and the CIMPR cargo receptor.
"Both AP-5 ζ and CIMPR are specifically brought down with SPG15-GFP."
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The isolated SPG15 cargo-binding fragment does not recruit AP5Z1.
"In contrast, TGN46 (used as a control) was not pulled down by the SPG15 construct, nor was the AP-5 ζ subunit, indicating that this domain of SPG15 does not interact with AP-5"
Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.
AP5Z1 primary-source research and annotation review notes