Vps53 (CG3338) is the Drosophila ortholog of VPS53, a large CATCHR-family helical-rod subunit shared by the GARP and EARP multisubunit tethering complexes. With Vps51 and Vps52 it forms the common core of GARP, which also contains Vps54 (scattered) and tethers endosome-derived carriers at the trans-Golgi network for retrograde retrieval of cargo such as lysosomal hydrolase receptors, and of EARP, which contains Vps50 (syndetin) instead and supports recycling of endocytosed cargo to the plasma membrane. Fly Vps53 co-purifies with the other GARP subunits on GTP-bound Arl5, Rab4 and Rab30 and co-precipitates with Vps50 in S2 cells. In larval salivary gland cells, Vps53 knockdown, like loss of other endosome-to-TGN retrograde transport components, leaves glue granules small and immature and sends them to early crinophagic degradation in lysosomes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000938 GARP complex | IBA GO_REF:0000033 | ACCEPT | Summary: Vps53 is a core subunit of the GARP tethering complex. Reason: Fly Vps53 (CG3338) co-purifies with Vps51, Vps52 and Vps54/scat on GTP-locked Arl5 and Rab columns; GARP membership is conserved from yeast to human (IBA/ISS donor human VPS53 Q5VIR6, yeast VPS53 S000003566; IEA from InterPro IPR039766). Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes |
| GO:0000938 GARP complex | IEA GO_REF:0000002 | ACCEPT | Summary: Vps53 is a core subunit of the GARP tethering complex. Reason: Fly Vps53 (CG3338) co-purifies with Vps51, Vps52 and Vps54/scat on GTP-locked Arl5 and Rab columns; GARP membership is conserved from yeast to human (IBA/ISS donor human VPS53 Q5VIR6, yeast VPS53 S000003566; IEA from InterPro IPR039766). Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes |
| GO:0000938 GARP complex | ISS GO_REF:0000024 | ACCEPT | Summary: Vps53 is a core subunit of the GARP tethering complex. Reason: Fly Vps53 (CG3338) co-purifies with Vps51, Vps52 and Vps54/scat on GTP-locked Arl5 and Rab columns; GARP membership is conserved from yeast to human (IBA/ISS donor human VPS53 Q5VIR6, yeast VPS53 S000003566; IEA from InterPro IPR039766). Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes |
| GO:0000938 GARP complex | NAS PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | ACCEPT | Summary: Vps53 is a core subunit of the GARP tethering complex. Reason: Fly Vps53 (CG3338) co-purifies with Vps51, Vps52 and Vps54/scat on GTP-locked Arl5 and Rab columns; GARP membership is conserved from yeast to human (IBA/ISS donor human VPS53 Q5VIR6, yeast VPS53 S000003566; IEA from InterPro IPR039766). Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes |
| GO:0000938 GARP complex | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps53 is a core subunit of the GARP tethering complex. Reason: Fly Vps53 (CG3338) co-purifies with Vps51, Vps52 and Vps54/scat on GTP-locked Arl5 and Rab columns; GARP membership is conserved from yeast to human (IBA/ISS donor human VPS53 Q5VIR6, yeast VPS53 S000003566; IEA from InterPro IPR039766). Supporting Evidence: PMID:25795912 Amongst the more abundant proteins that bound specifically to Arl5-GTP were the Drosophila orthologues of the four subunits of the GARP complex PMID:25453831 Most striking were Vps51, Vps52, and Vps53, three subunits of the GARP tethering complex that is found on the Golgi and involved in retrograde traffic from endosomes |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular function ND annotation: when it was made, no molecular function had been curated for this gene product from literature. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the molecular function is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: MODIFY. Re-checked 2026-10-31: the tethering papers cited in core_functions are on human GARP/EARP and a Rab-effector map (PMID:25795912, PMID:25799061, PMID:25453831). The term the earlier MODIFY proposed, vesicle membrane tethering activity, is kept as its own NEW row. Possibly stale: the 2026-11-06 ND citation pass found literature on this gene in this species that may identify a molecular function; see Vps53-notes.md, section "ND literature-search citations (2026-11-06)". A curator should check it before this ACCEPT stands. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | MODIFY | Summary: Golgi localization; correct but less specific than trans-Golgi network. Reason: GARP acts at the trans-Golgi network, as shown for the fly Vps52 subunit, and UniProt places Vps53 at the trans-Golgi network membrane. The more specific term trans-Golgi network (GO:0005802) is not yet annotated to Vps53 and is proposed as the replacement. ISS from human VPS53 (Q5VIR6); IEA from UniProt subcellular location. Proposed replacements: trans-Golgi network Supporting Evidence: file:DROME/Vps53/Vps53-uniprot.txt Golgi apparatus, trans-Golgi network |
| GO:0005794 Golgi apparatus | ISS GO_REF:0000024 | MODIFY | Summary: Golgi localization; correct but less specific than trans-Golgi network. Reason: GARP acts at the trans-Golgi network, as shown for the fly Vps52 subunit, and UniProt places Vps53 at the trans-Golgi network membrane. The more specific term trans-Golgi network (GO:0005802) is not yet annotated to Vps53 and is proposed as the replacement. ISS from human VPS53 (Q5VIR6); IEA from UniProt subcellular location. Proposed replacements: trans-Golgi network Supporting Evidence: file:DROME/Vps53/Vps53-uniprot.txt Golgi apparatus, trans-Golgi network |
| GO:0005829 cytosol | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Cytosolic pool of a peripheral membrane complex. Reason: GARP subunits cycle between membrane-bound and cytosolic pools; the functional locations are the TGN and endosome membranes, so cytosol is non-core. Inferred from the process annotation (GO_REF:0000108). |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome membrane localization from UniProt subcellular location mapping. Reason: As a shared EARP subunit, Vps53 is expected on recycling endosome membranes, and fly Vps53 associates with the endosomal Rab4-binding Vps50 subunit. Human VPS53 is relocated to endosomes by Rab4 overexpression. Supporting Evidence: PMID:25453831 We also examined a GARP subunit (Vps53) in mammalian cells and found that it could be relocated to endosomes by overexpression of Rab4 file:DROME/Vps53/Vps53-uniprot.txt SUBCELLULAR LOCATION: Endosome membrane |
| GO:0032456 endocytic recycling | ISS GO_REF:0000024 | ACCEPT | Summary: Vps53 is a shared subunit of EARP, which mediates endocytic recycling. Reason: Vps53 is shared by GARP and EARP; EARP (with Vps50/syndetin) supports recycling of internalized transferrin to the cell surface, and fly Vps53 co-precipitates with Vps50/CG4996. ISS from human VPS53 (Q5VIR6). Supporting Evidence: PMID:25799061 Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 |
| GO:0032456 endocytic recycling | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps53 is a shared subunit of EARP, which mediates endocytic recycling. Reason: Vps53 is shared by GARP and EARP; EARP (with Vps50/syndetin) supports recycling of internalized transferrin to the cell surface, and fly Vps53 co-precipitates with Vps50/CG4996. ISS from human VPS53 (Q5VIR6). Supporting Evidence: PMID:25799061 Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 |
| GO:0042147 retrograde transport, endosome to Golgi | IBA GO_REF:0000033 | ACCEPT | Summary: Vps53, as part of GARP, tethers endosome-derived vesicles at the TGN. Reason: Core process of GARP. In flies GARP (including Vps53) is recruited to the TGN by Arl5, and loss of Arl5 gives phenotypes consistent with an endosome-to-Golgi defect. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
| GO:0042147 retrograde transport, endosome to Golgi | IEA GO_REF:0000002 | ACCEPT | Summary: Vps53, as part of GARP, tethers endosome-derived vesicles at the TGN. Reason: Core process of GARP. In flies GARP (including Vps53) is recruited to the TGN by Arl5, and loss of Arl5 gives phenotypes consistent with an endosome-to-Golgi defect. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
| GO:0042147 retrograde transport, endosome to Golgi | NAS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | ACCEPT | Summary: Vps53, as part of GARP, tethers endosome-derived vesicles at the TGN. Reason: Core process of GARP. In flies GARP (including Vps53) is recruited to the TGN by Arl5, and loss of Arl5 gives phenotypes consistent with an endosome-to-Golgi defect. Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
| GO:1990745 EARP complex | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | NEW | Summary: Vps53 associates with the Vps50 (CG4996/Vps54L) subunit that defines the fly EARP (GARPII) complex. Reason: GFP-CG4996/Vps50 co-precipitated Myc-tagged Vps53 (CG3338) and Vps52 from S2 cells, and the four proteins co-purified on Rab4 columns, defining a Vps54-free version of GARP that corresponds to EARP. Vps51 already carries EARP complex by IBA; adding it here keeps the shared core subunits consistent. Supporting Evidence: PMID:25453831 These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996 PMID:25799061 The two complexes share the Ang2, Vps52 and Vps53 subunits |
| GO:7770062 vesicle membrane tethering activity | ISS PMID:25795912 The small G protein Arl5 contributes to endosome-to-Golgi tr... | NEW | Summary: Inferred vesicle membrane tethering activity for this gene product, proposed during the NO_DATA re-action pass. Reason: Vesicle membrane tethering activity is inferred for this gene product (ISS), not shown for it experimentally; the ND row for the aspect therefore stays (projects/NO_DATA.md). Vps53 contributes, as a subunit of GARP/EARP, to the vesicle-tethering activity of these complexes (contributes_to). Supporting Evidence: PMID:25795912 complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN) |
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Download this section (compressed HTML)Q: Are fly Vps53 loss-of-function phenotypes (e.g. in neurons or spermatogenesis) a combination of the scat (GARP) and Vps50 (EARP) phenotypes, as expected for a shared core subunit?
Experiment: Tissue-specific Vps53 RNAi with readouts for Lerp (M6PR) retrieval to the TGN and for endocytic recycling of a plasma-membrane cargo, compared with scat and Vps50 depletion.
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Download this section (compressed HTML)Vacuolar protein sorting 53 (Vps53) encodes a predicted component of the Golgi-Associated Retrograde Protein (GARP) complex. It is important for secretory granule maturation and for preventing early degradation of these granules.
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