Vps51

UniProt ID: Q8MSY4
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Vps51 (CG15087; Ang2/Fat-free in other species) is the Drosophila ortholog of VPS51, the small N-terminal coiled-coil subunit of the GARP and EARP multisubunit tethering complexes. With Vps52 and Vps53 it forms the core shared by GARP, which additionally contains Vps54 (scattered) and tethers endosome-derived carriers at the trans-Golgi network for retrograde transport of cargo such as lysosomal hydrolase receptors, and EARP, which contains Vps50 (syndetin) instead and supports recycling of endocytosed cargo to the plasma membrane. In Drosophila cell and head lysates Vps51 co-purifies with the other GARP subunits as an effector of GTP-bound Rab4, Rab6/Rab14 and the Arf-like GTPase Arl5.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000938 GARP complex
IBA
GO_REF:0000033
ACCEPT
Summary: Vps51 is a core subunit of the GARP tethering complex.
Reason: Fly Vps51 (CG15087) co-purifies with Vps52, Vps53 and Vps54/scat on GTP-locked Arl5 and Rab4 columns; GARP membership is the defining property of Vps51 and is conserved from yeast to human (IBA/ISS from human VPS51 Q9UID3).
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: Vps51 is a core subunit of the GARP tethering complex.
Reason: Fly Vps51 (CG15087) co-purifies with Vps52, Vps53 and Vps54/scat on GTP-locked Arl5 and Rab4 columns; GARP membership is the defining property of Vps51 and is conserved from yeast to human (IBA/ISS from human VPS51 Q9UID3).
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: Vps51 is a core subunit of the GARP tethering complex.
Reason: Fly Vps51 (CG15087) co-purifies with Vps52, Vps53 and Vps54/scat on GTP-locked Arl5 and Rab4 columns; GARP membership is the defining property of Vps51 and is conserved from yeast to human (IBA/ISS from human VPS51 Q9UID3).
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: Vps51 is a core subunit of the GARP tethering complex.
Reason: Fly Vps51 (CG15087) co-purifies with Vps52, Vps53 and Vps54/scat on GTP-locked Arl5 and Rab4 columns; GARP membership is the defining property of Vps51 and is conserved from yeast to human (IBA/ISS from human VPS51 Q9UID3).
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 Vps51-notes.md, section "ND literature-search citations (2026-11-06)". A curator should check it before this ACCEPT stands.
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 cytosolic pool of the Vps52 subunit increases when Arl5 is absent); the functional location is the TGN membrane, so cytosol is non-core. Inferred from the process annotation (GO_REF:0000108).
GO:0007030 Golgi organization
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Golgi organization inferred phylogenetically.
Reason: Loss of GARP perturbs Golgi structure secondarily (in fly spermatids, loss of the GARP subunit Vps54/scat disrupts the trans side of the acroblast Golgi), but this is a consequence of defective retrograde retrieval rather than a primary activity. IBA donor is zebrafish vps51 (ZDB-GENE-030131-6008).
Supporting Evidence:
PMID:27481842
these results suggest the importance of retrograde tethering complexes in the formation of a functional Golgi ribbon
GO:0007034 vacuolar transport
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: Vacuolar transport inferred phylogenetically.
Reason: Defects in GARP lead to missorting of vacuolar/lysosomal hydrolases because their sorting receptors are not retrieved to the TGN; vacuolar transport is a downstream consequence of the core endosome-to-Golgi role. No fly evidence; IBA donors human VPS51 (Q9UID3) and Arabidopsis AT4G02030.
GO:0016020 membrane
IBA
GO_REF:0000033
MODIFY
Summary: Generic membrane location.
Reason: Correct but uninformative; GARP, of which Vps51 is a core subunit, is a peripheral complex of the trans-Golgi network membrane (shown for the fly Vps52 subunit), so trans-Golgi network membrane (GO:0032588) is the more specific location. It is not yet annotated to Vps51. IBA donor human VPS51 (Q9UID3).
Proposed replacements: trans-Golgi network membrane
Supporting Evidence:
PMID:25795912
complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN)
GO:0032456 endocytic recycling
IBA
GO_REF:0000033
ACCEPT
Summary: Vps51 is a shared subunit of EARP, which mediates endocytic recycling.
Reason: As a subunit shared by GARP and EARP, Vps51 participates in EARP-dependent recycling of internalized cargo to the plasma membrane; this role is established for human EARP and the fly EARP (GARPII) complex contains Vps51. IBA/ISS donor human VPS51 (Q9UID3).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
GO:0032456 endocytic recycling
ISS
GO_REF:0000024
ACCEPT
Summary: Vps51 is a shared subunit of EARP, which mediates endocytic recycling.
Reason: As a subunit shared by GARP and EARP, Vps51 participates in EARP-dependent recycling of internalized cargo to the plasma membrane; this role is established for human EARP and the fly EARP (GARPII) complex contains Vps51. IBA/ISS donor human VPS51 (Q9UID3).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
GO:0032456 endocytic recycling
NAS
PMID:25795912
The small G protein Arl5 contributes to endosome-to-Golgi tr...
ACCEPT
Summary: Vps51 is a shared subunit of EARP, which mediates endocytic recycling.
Reason: As a subunit shared by GARP and EARP, Vps51 participates in EARP-dependent recycling of internalized cargo to the plasma membrane; this role is established for human EARP and the fly EARP (GARPII) complex contains Vps51. IBA/ISS donor human VPS51 (Q9UID3).
Supporting Evidence:
PMID:25799061
Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface.
GO:0042147 retrograde transport, endosome to Golgi
IBA
GO_REF:0000033
ACCEPT
Summary: Vps51, as part of GARP, tethers endosome-derived vesicles at the TGN.
Reason: Core process of GARP. In flies GARP (including Vps51) 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: Vps51, as part of GARP, tethers endosome-derived vesicles at the TGN.
Reason: Core process of GARP. In flies GARP (including Vps51) 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:0048193 Golgi vesicle transport
IBA
GO_REF:0000033
MODIFY
Summary: Golgi vesicle transport inferred phylogenetically.
Reason: Correct but general; the specific GARP process is retrograde transport, endosome to Golgi (GO:0042147), which is already annotated to Vps51 (IBA, NAS) and accepted. IBA donor zebrafish vps51 (ZDB-GENE-030131-6008).
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
IBA
GO_REF:0000033
ACCEPT
Summary: Vps51 is a shared subunit of the EARP complex.
Reason: EARP shares the Vps51(Ang2)-Vps52-Vps53 core with GARP; in flies the Vps50/CG4996 subunit co-purifies with Vps51-53 on Rab4 columns, defining a Vps54-free form of GARP (GARPII) that corresponds to EARP. IBA donor human VPS51 (Q9UID3).
Supporting Evidence:
PMID:25799061
The two complexes share the Ang2, Vps52 and Vps53 subunits
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: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). Vps51 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)

Core Functions

As a core subunit of GARP (with Vps54/scat), Vps51 contributes to tethering of endosome-derived carriers at the trans-Golgi network for retrograde endosome-to-Golgi transport.

Cellular Locations:
In Complex:
GARP complex
Supporting Evidence:
  • PMID:25795912
    complex that acts in the tethering of vesicles moving from endosomes to the trans-Golgi network (TGN)
  • 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

As a core subunit of EARP (with Vps50), Vps51 contributes to tethering of carriers at recycling endosomes for recycling of internalized cargo to the plasma membrane.

Directly Involved In:
Cellular Locations:
In Complex:
EARP complex
Supporting Evidence:
  • 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.
  • PMID:25453831
    These results suggest that the GARP complex exists in a second version in which Vps54 is replaced by CG4996

References

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Suggested Questions for Experts

Q: Does Drosophila Vps51 mediate GARP/EARP binding to SNAREs (e.g. Syx16, Syx6) as its yeast and human orthologs do, and is it needed for assembly of both complexes in vivo?

Suggested Experiments

Experiment: Generate Vps51 null mutants and test GARP and EARP integrity (co-immunoprecipitation of Vps52/Vps53 with scat and Vps50), Lerp retrieval to the TGN, and male fertility.

Deep Research

Falcon

(Vps51-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Vps51-notes.md)

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