Vps29 (CG4764) is the Drosophila ortholog of VPS29, a small catalytically inactive metallophosphoesterase-fold subunit of the retromer cargo-selective complex (Vps35-Vps26-Vps29), which retrieves transmembrane cargo from endosomes to the trans-Golgi network or the plasma membrane. Vps29 binds the C-terminal region of Vps35 and serves as a platform for regulators such as the Rab7 GAP TBC1D5; by homology it is also a subunit of the related retriever complex, which together with the CCC subcomplex forms the larger commander complex for retromer-independent endosomal recycling. In flies Vps29 is dispensable for embryogenesis but required for retromer function in adults: without it Vps35 and Vps26 still assemble but retromer is mislocalized from the neuropil to neuronal cell bodies together with Rab7, leading to synaptic vesicle endocytosis and transmission defects at the neuromuscular junction, retinal degeneration and age-dependent endolysosomal dysfunction. In the larval fat body mCherry-Vps29 forms Vps35-dependent puncta that associate mainly with Rab4/Rab5 early endosomes, and human VPS29 can substitute for the fly protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Generic location; less specific than the endosome localization. Reason: Correct but less specific than the evidence supports: Vps29 is a peripheral protein of the retromer coat on endosomes, and endosome (GO:0005768) is already annotated to Vps29 (IBA, ISS, IEA), as are endosome membrane and late endosome membrane. Proposed replacements: endosome Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Retromer acts on endosomes. Reason: Correct location of the cargo-selective complex; more specific late endosome membrane is also annotated (IDA). Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0005768 endosome | IEA GO_REF:0000117 | ACCEPT | Summary: Retromer acts on endosomes. Reason: Correct location of the cargo-selective complex; more specific late endosome membrane is also annotated (IDA). Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0005768 endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Retromer acts on endosomes. Reason: Correct location of the cargo-selective complex; more specific late endosome membrane is also annotated (IDA). Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0005829 cytosol | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Cytosolic pool of a peripheral membrane complex. Reason: Retromer cycles between cytosol and endosome membranes; the functional location is the endosome. Inferred from the process annotation (GO_REF:0000108). |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome membrane, from UniProt subcellular-location mapping. Reason: Vps29 is a peripheral membrane protein of the retromer coat on endosomes. Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0012505 endomembrane system | NAS PMID:26172538 Retromer Ensures the Degradation of Autophagic Cargo by Main... | MODIFY | Summary: Generic location; less specific than the endosome localization. Reason: Correct but less specific than the evidence supports: Vps29 is a peripheral protein of the retromer coat on endosomes, and endosome (GO:0005768) is already annotated to Vps29 (IBA, ISS, IEA), as are endosome membrane and late endosome membrane. Proposed replacements: endosome Supporting Evidence: file:DROME/Vps29/Vps29-uniprot.txt Endosome membrane |
| GO:0030904 retromer complex | IBA GO_REF:0000033 | MODIFY | Summary: Retromer complex; correct but less specific than the cargo-selective subcomplex. Reason: Vps29 is a subunit of the Vps35-Vps26-Vps29 cargo-selective trimer of retromer; retromer, cargo-selective complex (GO:0030906) is already annotated to Vps29 (ISS). Proposed replacements: retromer, cargo-selective complex Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:0030904 retromer complex | IEA GO_REF:0000002 | MODIFY | Summary: Retromer complex; correct but less specific than the cargo-selective subcomplex. Reason: Vps29 is a subunit of the Vps35-Vps26-Vps29 cargo-selective trimer of retromer; retromer, cargo-selective complex (GO:0030906) is already annotated to Vps29 (ISS). Proposed replacements: retromer, cargo-selective complex Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:0030904 retromer complex | NAS PMID:26172538 Retromer Ensures the Degradation of Autophagic Cargo by Main... | MODIFY | Summary: Retromer complex; correct but less specific than the cargo-selective subcomplex. Reason: Vps29 is a subunit of the Vps35-Vps26-Vps29 cargo-selective trimer of retromer; retromer, cargo-selective complex (GO:0030906) is already annotated to Vps29 (ISS). Proposed replacements: retromer, cargo-selective complex Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:0030906 retromer, cargo-selective complex | ISS GO_REF:0000024 | ACCEPT | Summary: Vps29 is a core subunit of the retromer cargo-selective complex. Reason: Conserved trimer subunit (ISS from yeast VPS29); in fly Vps29 is required for proper retromer localization. Supporting Evidence: PMID:32286230 Our results reveal the role of Vps29 in retromer localization and function |
| GO:0031594 neuromuscular junction | IDA PMID:32286230 Retromer subunit, VPS29, regulates synaptic transmission and... | KEEP AS NON CORE | Summary: Vps29 is required for retromer function at the neuromuscular junction. Reason: Vps29 is needed for retromer (Vps35) localization to synaptic boutons; NMJ is a valid, specific site of activity in neurons but peripheral to the core endosomal function. Supporting Evidence: PMID:32286230 our results (above) establish a largely conserved Vps29 requirement for retromer function in the retina and at the NMJ synapse |
| GO:0031594 neuromuscular junction | IMP PMID:32286230 Retromer subunit, VPS29, regulates synaptic transmission and... | KEEP AS NON CORE | Summary: Vps29 is required for retromer function at the neuromuscular junction. Reason: Vps29 is needed for retromer (Vps35) localization to synaptic boutons; NMJ is a valid, specific site of activity in neurons but peripheral to the core endosomal function. Supporting Evidence: PMID:32286230 our results (above) establish a largely conserved Vps29 requirement for retromer function in the retina and at the NMJ synapse |
| GO:0031902 late endosome membrane | IDA PMID:22791894 Type II phosphatidylinositol 4-kinase regulates trafficking ... | ACCEPT | Summary: Vps29 on late endosome membranes in salivary glands. Reason: The cited study analyses retromer dynamics on late endosomes and tubular endosomes that retrieve Lerp to the TGN; only the abstract is cached, and the curator's IDA is accepted. Supporting Evidence: PMID:22791894 it is required for normal retromer dynamics and for formation of tubular endosomes |
| GO:0032456 endocytic recycling | NAS PMID:26172538 Retromer Ensures the Degradation of Autophagic Cargo by Main... | ACCEPT | Summary: Retromer also recycles cargo to the plasma membrane. Reason: The retromer cargo-selective complex, including Vps29, recycles proteins within the endolysosomal system, including back to the cell surface. Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:0042147 retrograde transport, endosome to Golgi | IBA GO_REF:0000033 | ACCEPT | Summary: Core retromer process. Reason: Vps29 is required for retromer function; conserved endosome-to-Golgi retrieval role of the cargo-selective complex (IBA donors yeast and fission yeast VPS29). Supporting Evidence: PMID:26172538 Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network |
| GO:0042147 retrograde transport, endosome to Golgi | IEA GO_REF:0000002 | ACCEPT | Summary: Core retromer process. Reason: Vps29 is required for retromer function; conserved endosome-to-Golgi retrieval role of the cargo-selective complex (IBA donors yeast and fission yeast VPS29). Supporting Evidence: PMID:26172538 Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network |
| GO:0042147 retrograde transport, endosome to Golgi | ISS GO_REF:0000024 | ACCEPT | Summary: Core retromer process. Reason: Vps29 is required for retromer function; conserved endosome-to-Golgi retrieval role of the cargo-selective complex (IBA donors yeast and fission yeast VPS29). Supporting Evidence: PMID:26172538 Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network |
| GO:0042147 retrograde transport, endosome to Golgi | NAS PMID:26172538 Retromer Ensures the Degradation of Autophagic Cargo by Main... | ACCEPT | Summary: Core retromer process. Reason: Vps29 is required for retromer function; conserved endosome-to-Golgi retrieval role of the cargo-selective complex (IBA donors yeast and fission yeast VPS29). Supporting Evidence: PMID:26172538 Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network |
| GO:0046718 symbiont entry into host cell | HMP PMID:30445201 Identification of insect genes involved in baculovirus AcMNP... | KEEP AS NON CORE | Summary: Vps29 knockdown reduced baculovirus entry in an RNAi screen in fly cells. Reason: A host requirement in a trafficking-focused RNAi screen for AcMNPV entry; plausibly an indirect effect of disturbed endosomal trafficking. Only the abstract is cached, which does not name the individual hits, so the curator's annotation is retained as non-core. Supporting Evidence: PMID:30445201 We identified 24 genes required for efficient virus entry and reporter expression |
| GO:0098796 membrane protein complex | IEA GO_REF:0000117 | MODIFY | Summary: Generic membrane protein complex; less specific than the retromer cargo-selective complex. Reason: Correct but uninformative; retromer, cargo-selective complex (GO:0030906) is already annotated to Vps29 (ISS). Proposed replacements: retromer, cargo-selective complex Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:0140312 cargo adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Vps29 contributes to the cargo-adaptor activity of the retromer trimer. Reason: The cargo-selective complex recognizes transmembrane cargo and links it to the sorting-nexin coat; Vps29 contributes as a structural subunit (contributes_to). IBA donor yeast VPS29. Supporting Evidence: PMID:32286230 Retromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IDA PMID:32286230 Retromer subunit, VPS29, regulates synaptic transmission and... | KEEP AS NON CORE | Summary: Vps29 mutant NMJs show impaired synaptic vesicle endocytosis. Reason: Reduced FM1-43 uptake at Vps29 mutant NMJs reflects a requirement for retromer function at the synapse; a tissue-level consequence rather than the core molecular role. Supporting Evidence: PMID:32286230 Vps291 NMJs show reduced FM 1-43 dye uptake following KCl stimulation, consistent with impaired synaptic vesicle endocytosis. |
| GO:1900242 regulation of synaptic vesicle endocytosis | IMP PMID:32286230 Retromer subunit, VPS29, regulates synaptic transmission and... | KEEP AS NON CORE | Summary: Vps29 mutant NMJs show impaired synaptic vesicle endocytosis. Reason: Reduced FM1-43 uptake at Vps29 mutant NMJs reflects a requirement for retromer function at the synapse; a tissue-level consequence rather than the core molecular role. Supporting Evidence: PMID:32286230 Vps291 NMJs show reduced FM 1-43 dye uptake following KCl stimulation, consistent with impaired synaptic vesicle endocytosis. |
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Download this section (compressed HTML)Q: Does fly Vps29 also act in a retriever (Vps35L-Vps26C-Vps29) complex, and do some Vps29 mutant phenotypes reflect loss of retriever rather than retromer?
Experiment: Test whether Vps29 point mutants that abolish TBC1D5 binding but preserve Vps35 binding reproduce the neuronal retromer-mislocalization phenotype of Vps29 nulls.
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Download this section (compressed HTML)Vacuolar protein sorting 29 (Vps29) encodes a subunit of the retromer complex involved in cargo recognition and recycling from endosomes to the trans-Golgi network or plasma membrane.
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