Vps50

UniProt ID: A1ZAY8
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Vps50 (CG4996; also called Vps54L, ortholog of human VPS50/syndetin/CCDC132) is the subunit that defines the endosome-associated recycling protein (EARP) complex. It is distantly related to Vps54 and replaces it on the shared Vps51-Vps52-Vps53 core, converting the Golgi-associated GARP tether into an endosomal tether. In Drosophila S2 cells Vps50 co-purifies with Vps51-Vps53 as an effector of GTP-bound Rab4 and Rab14, co-localizes with Rab4 on endosomes and co-precipitates with Vps52 and Vps53. By analogy with mammalian syndetin, EARP engages the SNARE syntaxin 6 and supports recycling of internalized cargo from endosomes to the plasma membrane, rather than endosome-to-Golgi retrograde traffic. Vps50 null flies are viable and male fertile, but adult class IV sensory neurons show reduced dendrite regrowth after developmental pruning, a milder phenotype than loss of the GARP-specific Vps54.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000149 SNARE binding
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: SNARE binding inferred from human VPS50/syndetin.
Reason: Human EARP binds syntaxin 6 and cognate SNAREs, which is part of its tethering mechanism; this is plausible for fly Vps50 but untested, and is better represented by the complex's tethering activity. IBA donor human VPS50 (Q96JG6).
Supporting Evidence:
PMID:25799061
EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs.
GO:0000938 GARP complex
IDA
PMID:25453831
Toward a comprehensive map of the effectors of rab GTPases.
MODIFY
Summary: Vps50 is part of the Vps54-free form of GARP described as GARPII, which corresponds to EARP.
Reason: The cited paper found CG4996 co-purifying with Vps51-53 in place of Vps54 and named the resulting complex GARPII. This complex was subsequently defined in mammals as EARP, which has its own GO term (GO:1990745); GARP complex (GO:0000938) refers to the Vps54-containing complex. The correct location for Vps50 is EARP complex.
Proposed replacements: EARP complex
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
EARP contains an uncharacterized protein, syndetin, in place of the Vps54 subunit of GARP
GO:0000938 GARP complex
NAS
PMID:25453831
Toward a comprehensive map of the effectors of rab GTPases.
MODIFY
Summary: Vps50 is part of the Vps54-free form of GARP described as GARPII, which corresponds to EARP.
Reason: The cited paper found CG4996 co-purifying with Vps51-53 in place of Vps54 and named the resulting complex GARPII. This complex was subsequently defined in mammals as EARP, which has its own GO term (GO:1990745); GARP complex (GO:0000938) refers to the Vps54-containing complex. The correct location for Vps50 is EARP complex.
Proposed replacements: EARP complex
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
EARP contains an uncharacterized protein, syndetin, in place of the Vps54 subunit of GARP
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 EARP and a Rab-effector map (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 Vps50-notes.md, section "ND literature-search citations (2026-11-06)". A curator should check it before this ACCEPT stands.
GO:0005768 endosome
IDA
PMID:25453831
Toward a comprehensive map of the effectors of rab GTPases.
ACCEPT
Summary: GFP-Vps50 colocalizes with Rab4 on endosomes in S2 cells.
Reason: Direct localization of the fly protein with the endosomal Rab4 and Hrs-labelled compartment.
Supporting Evidence:
PMID:25453831
GFP-tagged CG4996 colocalized with Rab4 in S2 cells
GO:0005829 cytosol
IEA
GO_REF:0000108
KEEP AS NON CORE
Summary: Cytosolic pool of a peripheral membrane complex.
Reason: Tethering-complex subunits cycle between membrane-bound and cytosolic pools; the functional location is the endosome membrane, so cytosol is non-core. Inferred from the (over-annotated) endosome-to-Golgi process annotation (GO_REF:0000108).
GO:0032456 endocytic recycling
IBA
GO_REF:0000033
ACCEPT
Summary: EARP, defined by Vps50/syndetin, acts in endocytic recycling.
Reason: Depletion of syndetin, the human ortholog of Vps50, delays transferrin recycling to the cell surface; endocytic recycling is the core process of EARP. The fly protein binds the recycling-associated Rab4 and localizes with it on endosomes. IBA/ISS donors human VPS50 (Q96JG6) and mouse Vps50 (MGI:1920538).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
PMID:25453831
GFP-tagged CG4996 colocalized with Rab4 in S2 cells and interacted with GARP subunits by coprecipitation
GO:0032456 endocytic recycling
IEA
GO_REF:0000002
ACCEPT
Summary: EARP, defined by Vps50/syndetin, acts in endocytic recycling.
Reason: Depletion of syndetin, the human ortholog of Vps50, delays transferrin recycling to the cell surface; endocytic recycling is the core process of EARP. The fly protein binds the recycling-associated Rab4 and localizes with it on endosomes. IBA/ISS donors human VPS50 (Q96JG6) and mouse Vps50 (MGI:1920538).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
PMID:25453831
GFP-tagged CG4996 colocalized with Rab4 in S2 cells and interacted with GARP subunits by coprecipitation
GO:0032456 endocytic recycling
ISS
GO_REF:0000024
ACCEPT
Summary: EARP, defined by Vps50/syndetin, acts in endocytic recycling.
Reason: Depletion of syndetin, the human ortholog of Vps50, delays transferrin recycling to the cell surface; endocytic recycling is the core process of EARP. The fly protein binds the recycling-associated Rab4 and localizes with it on endosomes. IBA/ISS donors human VPS50 (Q96JG6) and mouse Vps50 (MGI:1920538).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
PMID:25453831
GFP-tagged CG4996 colocalized with Rab4 in S2 cells and interacted with GARP subunits by coprecipitation
GO:0032456 endocytic recycling
NAS
PMID:25795912
The small G protein Arl5 contributes to endosome-to-Golgi tr...
ACCEPT
Summary: EARP, defined by Vps50/syndetin, acts in endocytic recycling.
Reason: Depletion of syndetin, the human ortholog of Vps50, delays transferrin recycling to the cell surface; endocytic recycling is the core process of EARP. The fly protein binds the recycling-associated Rab4 and localizes with it on endosomes. IBA/ISS donors human VPS50 (Q96JG6) and mouse Vps50 (MGI:1920538).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
PMID:25453831
GFP-tagged CG4996 colocalized with Rab4 in S2 cells and interacted with GARP subunits by coprecipitation
GO:0042147 retrograde transport, endosome to Golgi
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: Endosome-to-Golgi retrograde transport is the function of GARP (Vps54), not of Vps50-containing EARP.
Reason: Depletion of syndetin, the human Vps50 ortholog, did not affect retrograde transport of Shiga toxin B subunit to the Golgi or TGN46 localization; the retrograde process belongs to GARP, which contains Vps54/scat instead of Vps50. The IEA (InterPro IPR040047) and NAS rows transfer a GARP property to the EARP-specific subunit.
Supporting Evidence:
PMID:25799061
These experiments thus demonstrated that, unlike GARP, the Syndetin-containing complex is not involved in retrograde transport from endosomes to the TGN.
GO:0042147 retrograde transport, endosome to Golgi
NAS
PMID:25795912
The small G protein Arl5 contributes to endosome-to-Golgi tr...
MARK AS OVER ANNOTATED
Summary: Endosome-to-Golgi retrograde transport is the function of GARP (Vps54), not of Vps50-containing EARP.
Reason: Depletion of syndetin, the human Vps50 ortholog, did not affect retrograde transport of Shiga toxin B subunit to the Golgi or TGN46 localization; the retrograde process belongs to GARP, which contains Vps54/scat instead of Vps50. The IEA (InterPro IPR040047) and NAS rows transfer a GARP property to the EARP-specific subunit.
Supporting Evidence:
PMID:25799061
These experiments thus demonstrated that, unlike GARP, the Syndetin-containing complex is not involved in retrograde transport from endosomes to the TGN.
GO:1990745 EARP complex
IBA
GO_REF:0000033
ACCEPT
Summary: Vps50 is the defining subunit of the EARP complex.
Reason: Fly Vps50/CG4996 associates with the Vps51-Vps53 core in place of Vps54, as mammalian syndetin does in EARP. IBA donor human VPS50 (Q96JG6); IEA from InterPro IPR040047.
Supporting Evidence:
PMID:25453831
These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996
GO:1990745 EARP complex
IEA
GO_REF:0000002
ACCEPT
Summary: Vps50 is the defining subunit of the EARP complex.
Reason: Fly Vps50/CG4996 associates with the Vps51-Vps53 core in place of Vps54, as mammalian syndetin does in EARP. IBA donor human VPS50 (Q96JG6); IEA from InterPro IPR040047.
Supporting Evidence:
PMID:25453831
These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996
GO:7770062 vesicle membrane tethering activity
ISS
PMID:25799061
EARP is a multisubunit tethering complex involved in endocyt...
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). Vps50 contributes, as the defining subunit of EARP, to the vesicle-tethering activity of the complex (contributes_to).
Supporting Evidence:
PMID:25799061
These findings implicate EARP in canonical membrane-fusion events in the process of endocytic recycling.

Core Functions

As the defining subunit of the EARP tethering complex, Vps50 directs the shared Vps51-Vps52-Vps53 core to Rab4-positive endosomes and contributes to tethering of carriers that recycle internalized cargo to the plasma membrane.

Directly Involved In:
In Complex:
EARP complex
Supporting Evidence:
  • PMID:25453831
    GFP-tagged CG4996 colocalized with Rab4 in S2 cells and interacted with GARP subunits by coprecipitation
  • PMID:25799061
    Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
  • PMID:25799061
    This change determines differential localization of EARP to recycling endosomes and GARP to the Golgi complex.

References

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Suggested Questions for Experts

Q: Which cargoes depend on Vps50/EARP for recycling in Drosophila tissues, and does fly EARP function in dense-core vesicle maturation in neurons as reported for worm and mouse EARP?

Suggested Experiments

Experiment: Generate Vps50 null flies and measure recycling of endocytosed cargo (e.g. in nephrocytes or S2 cells) and Rab4-endosome morphology, contrasting with scat (GARP) mutants.

Deep Research

Falcon

(Vps50-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Vps50-notes.md)

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