Rab7 (mouse, Rab7a) — Review Notes

UniProt: P51150 (RAB7A_MOUSE), 207 aa. Official MGI symbol Rab7a (MGI:105068),
historical/synonym symbol Rab7. Directory and files use the Rab7 prefix (as
fetched). NCBI taxon 10090.

Summary of gene function

Mouse Rab7 (Rab7a) is the direct ortholog of human RAB7A and is functionally identical:
a Rab-family small GTPase (EC 3.6.5.2) that acts as the master regulator of the late
endocytic pathway. It cycles between an inactive GDP-bound (cytosolic) state and an
active GTP-bound (membrane-associated) state. When GTP-loaded by the Mon1–Ccz1 GEF on
maturing endosomes (Rab5→Rab7 conversion), it recruits effectors (RILP, HOPS,
retromer, FYCO1, PLEKHM1, ORP1L) to drive late endosome–lysosome fusion,
autophagosome–lysosome fusion, phagosome maturation, retrograde endosome→Golgi
transport, and lysosome positioning. It is inactivated by TBC-domain GAPs.

The mouse-specific experimental literature emphasizes physiological roles:
- Lipophagy / β-adrenergic lipolysis in adipocytes PMID:23708524.
- Synaptic AMPA-receptor trafficking and LTD in neurons PMID:24217640.
- Osteoclast bone resorption / ruffled border via PLEKHM1/DEF8 and RUFY4
[PMID:27777970, PMID:38744829, PMID:22467241].
- Secretory-lysosome trafficking via V-ATPase a3-mediated Rab7 recruitment
PMID:29712939.
- Numerous late-endosome/lysosome co-localization studies (TrkB/NHE6, TrkA/Nedd4-2,
BACE1, TMEM127, WASH/strumpellin, C9ORF72, etc.).

2026-07-19 SynGO revisit

The SynGO annotations from PMID:24217640 were revisited during the human/mouse
RAB7A/Rab7a comparison for the Deliverome project. The accessible paper text
supports AMPA-receptor routing from early endosomes toward late
endosomal/lysosomal compartments during LTD [PMID:24217640 Stargazin regulates
AMPA receptor trafficking through adaptor protein complexes during long-term
depression, "transport from the cell surface to early endosomes and from early
endosomes to late endosomes/lysosomes"]. However, the experimentally centered
actors in the accessible text are stargazin, AP-2, and AP-3A, not Rab7. I
therefore changed the four cached SynGO review rows from UNDECIDED to
KEEP_AS_NON_CORE, retaining them as indirect neuronal-context annotations
rather than core Rab7 biology.

Key requested reference

PMID:41814093 Jozić et al. (2026) Nature Biotechnology,
"In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP
delivery." DOI: 10.1038/s41587-026-03022-6.
- Used LysoTag mice for immunoisolation of liver lysosomes and lysosomal
proteomics to quantify endosomal escape of lipid nanoparticles (LNPs) in vivo.
- Key Rab7 finding: "Loss of Rab7, a mediator of late endosomal maturation,
increased LNP escape."
In vivo evidence (mouse liver) that Rab7 is a mediator of
late endosomal maturation and that its loss diverts cargo away from the
degradative lysosomal route, increasing cytosolic escape.
- This supports the core Rab7 functions of late-endosome maturation
(early→late endosome transport, endosome→lysosome transport) in an intact mouse.
- Added as a reference and cited as supporting evidence on the relevant
maturation/transport annotations.

Deep research provider status

Automated deep research could not be run in this environment: the Falcon
provider requires the agentapi binary (not in PATH), and the
OpenAI/Perplexity/Anthropic providers require API keys that are unset. No
-deep-research-{provider}.md file was fabricated (per project policy). A manual,
fully-cited synthesis was written to Rab7-deep-research-manual.md instead.

Annotation review approach

119 GOA annotations seeded. The biology mirrors human RAB7A
(genes/human/RAB7A/RAB7A-ai-review.yaml). Decisions:
- ACCEPT core MF (GTPase activity, G protein activity, GTP/GDP binding) and core
CC/BP (late endosome, lysosome, endosome→lysosome transport, retromer, retrograde
transport, autophagy/lipophagy, phagosome maturation).
- REMOVE all GO:0005515 protein binding (uninformative per curation guidelines);
the underlying effector interactions are captured by specific terms.
- KEEP_AS_NON_CORE for tissue/context-specialized roles (synaptic, bone resorption,
melanosome, mitophagy, exosome, viral, sterol sensing, EGF catabolism).
- MARK_AS_OVER_ANNOTATED for Golgi apparatus (GO:0005794, IDA from a bulk Golgi
membrane proteomics study PMID:11042173) — Rab7 is a late-endosome/lysosome
protein and this is most consistent with co-fractionation/contamination rather
than a genuine steady-state Golgi pool.