Mouse Rab7 (official symbol Rab7a; UniProt P51150) is a Rab-family small GTPase (EC 3.6.5.2) and the direct ortholog of human RAB7A. It is the master regulator of the late endocytic pathway, cycling between an inactive GDP-bound (cytosolic) state and an active GTP-bound (membrane-associated) state. GTP-loading by the Mon1-Ccz1 GEF on maturing endosomes (the Rab5-to-Rab7 conversion) recruits effectors including RILP, the HOPS tethering complex, retromer, FYCO1, PLEKHM1 and ORP1L to drive early-to-late endosome maturation, late endosome-lysosome fusion, autophagosome-lysosome fusion, phagosome maturation, retrograde endosome-to-Golgi transport and lysosome positioning. It is inactivated by TBC-domain GAPs. Mouse studies have established physiological roles in lipophagy and beta-adrenergic lipolysis in adipocytes, synaptic AMPA-receptor trafficking during long-term depression in neurons, osteoclast ruffled-border function and bone resorption, and secretory-lysosome trafficking. In vivo work in mouse liver using LysoTag mice further confirms Rab7 as a mediator of late endosomal maturation, where its loss diverts cargo away from the degradative route and increases the cytosolic escape of lipid nanoparticles (PMID:41814093).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: Rab7 is a canonical lysosomal marker and effector platform. UniProt lists lysosome membrane localization with experimental support across orthologs. Reason: Core localization where Rab7 exerts its regulatory function in fusion and cargo degradation; supported by phylogenetic conservation and experimental data in mouse. |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Late endosome is the canonical site of active Rab7, where it is GTP-loaded by Mon1-Ccz1 during the Rab5-to-Rab7 conversion. Reason: Defining core localization for Rab7, confirmed by many mouse IDA studies in this review. |
| GO:0008333 endosome to lysosome transport | IBA GO_REF:0000033 | ACCEPT | Summary: The core biological process for Rab7: it controls maturation of late endosomes and their fusion with lysosomes for cargo degradation. In vivo mouse liver data confirm Rab7 as a mediator of late endosomal maturation. Reason: Core biological function, strongly supported across orthologs and directly in mouse. Supporting Evidence: PMID:41814093 Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape. file:mouse/Rab7/Rab7-deep-research-manual.md Manual synthesis of mouse Rab7/Rab7a literature supports the conserved late-endosome maturation and endosome-to-lysosome routing function. |
| GO:0045335 phagocytic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Rab7 is recruited to phagosomes and regulates phagosome maturation. Reason: Core function in phagosome maturation; conserved across the Rab7 ortholog group. |
| GO:0090385 phagosome-lysosome fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Rab7 is required for phagosome-lysosome fusion and phagolysosome maturation. Reason: Core function in innate immunity / pathogen degradation, conserved across orthologs. |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to autophagosome membranes and is required for autophagosome-lysosome fusion. Reason: Core localization for the autophagy role of Rab7; consistent with phagophore assembly site annotation in this review. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Rab7 has intrinsic GTPase activity (EC 3.6.5.2) hydrolyzing GTP to GDP, accelerated by TBC-domain GAPs. Reason: Core molecular function, fundamental to the molecular-switch behavior; directly demonstrated for mouse Rab7 (PMID:16855591). |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: Rab7 functions as a G protein, cycling between active GTP-bound and inactive GDP-bound states to regulate membrane trafficking. Reason: Accurate core molecular function for a Rab-family small GTPase. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GTP binding activates Rab7 and enables membrane association and effector recruitment. Reason: Core molecular function of the GTPase cycle. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to lysosomal membranes as a peripheral membrane protein on the cytoplasmic face. Reason: Core localization, confirmed experimentally in mouse (e.g. PMID:28063257). |
| GO:0005770 late endosome | IEA GO_REF:0000117 | ACCEPT | Summary: Late endosome localization predicted by ARBA, consistent with abundant experimental evidence. Reason: Canonical core localization. |
| GO:0005811 lipid droplet | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to lipid droplets during lipophagy, directly demonstrated in mouse adipocytes. Reason: Valid localization related to lipophagy; experimentally supported in mouse (PMID:23708524). |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to endosome membranes, primarily late endosome membranes. Reason: Accurate localization; the more specific late endosome membrane term is also annotated. |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to phagosomal membranes during phagosome maturation. Reason: Core localization for the phagosome maturation function. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: Rab7 localizes to multiple types of cytoplasmic vesicles. Reason: Accurate but general; more specific vesicle annotations are present. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Late endosome membrane is the canonical site for active Rab7. Reason: Core localization where Rab7 recruits effectors for maturation and transport. |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Rab7 can be recruited to mitochondrial membranes during mitophagy and at ER-mitochondria/endosome contact sites. Reason: Context-dependent localization during mitophagy rather than constitutive mitochondrial residence. |
| GO:0033162 melanosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Rab7 localizes to melanosome membranes; melanosomes are lysosome-related organelles. Reason: Cell-type-specific localization relevant to melanocyte biology and lysosome-related organelle biogenesis. |
| GO:0098588 bounding membrane of organelle | IEA GO_REF:0000117 | ACCEPT | Summary: Rab7 localizes to the bounding membranes of various organelles as a peripheral membrane protein. Reason: Accurate general localization consistent with Rab7 membrane-association pattern. |
| GO:0005765 lysosomal membrane | ISO GO_REF:0000096 | ACCEPT | Summary: Lysosomal membrane localization transferred from experimentally characterized orthologs. Reason: Core localization, well supported. |
| GO:0005765 lysosomal membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Lysosomal membrane localization transferred from human ortholog. Reason: Core localization, consistent with mouse experimental data. |
| GO:0031902 late endosome membrane | ISO GO_REF:0000096 | ACCEPT | Summary: Late endosome membrane localization transferred from orthologs. Reason: Core localization. |
| GO:0031902 late endosome membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Late endosome membrane localization transferred from human ortholog. Reason: Core localization. |
| GO:0033162 melanosome membrane | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Melanosome membrane localization transferred from human ortholog. Reason: Cell-type-specific localization in melanocytes (lysosome-related organelle). |
| GO:0003924 GTPase activity | ISO GO_REF:0000119 | ACCEPT | Summary: GTPase activity transferred from human ortholog; also directly demonstrated for mouse Rab7. Reason: Core molecular function. |
| GO:0003925 G protein activity | ISO GO_REF:0000119 | ACCEPT | Summary: G protein (molecular switch) activity transferred from human ortholog. Reason: Core molecular function for a Rab GTPase. |
| GO:0005525 GTP binding | ISO GO_REF:0000096 | ACCEPT | Summary: GTP binding transferred from experimentally characterized orthologs. Reason: Core molecular function. |
| GO:0005525 GTP binding | ISO GO_REF:0000119 | ACCEPT | Summary: GTP binding transferred from human ortholog. Reason: Core molecular function. |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Mitochondrial association during mitophagy / at contact sites, transferred from human ortholog. Reason: Context-dependent localization, not constitutive. |
| GO:0005764 lysosome | ISO GO_REF:0000119 | ACCEPT | Summary: Lysosome colocalization transferred from human ortholog. Reason: Core localization. |
| GO:0005764 lysosome | ISO GO_REF:0000119 | ACCEPT | Summary: Lysosome localization transferred from human ortholog. Reason: Core localization. |
| GO:0005765 lysosomal membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Active Rab7 functions on the lysosomal membrane (ortholog transfer). Reason: Core site of action. |
| GO:0005770 late endosome | ISO GO_REF:0000119 | ACCEPT | Summary: Late endosome colocalization transferred from human ortholog. Reason: Core localization. |
| GO:0005770 late endosome | ISO GO_REF:0000096 | ACCEPT | Summary: Late endosome localization transferred from orthologs. Reason: Canonical core localization. |
| GO:0005770 late endosome | ISO GO_REF:0000119 | ACCEPT | Summary: Late endosome localization transferred from human ortholog. Reason: Canonical core localization. |
| GO:0006622 protein targeting to lysosome | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 targets cargo proteins to the lysosome for degradation (ortholog transfer). Reason: Core function in degradative trafficking. |
| GO:0007174 epidermal growth factor catabolic process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 mediates EGF/EGFR degradation through the endolysosomal pathway. Reason: Specific instance of the general endosome-to-lysosome degradative function. |
| GO:0008333 endosome to lysosome transport | ISO GO_REF:0000119 | ACCEPT | Summary: Endosome-to-lysosome transport transferred from human ortholog. Reason: Core biological function. |
| GO:0009617 response to bacterium | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 participates in responses to intracellular bacteria via phagosome maturation. Reason: Downstream physiological consequence of the core phagosome maturation function. |
| GO:0010008 endosome membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Active Rab7 functions on the endosome membrane (ortholog transfer). Reason: Core site of action. |
| GO:0010008 endosome membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Endosome membrane localization transferred from human ortholog. Reason: Core localization. |
| GO:0019003 GDP binding | ISO GO_REF:0000096 | ACCEPT | Summary: Rab7 binds GDP in its inactive cytosolic state (ortholog transfer). Reason: Core molecular function of the GTPase cycle. |
| GO:0019003 GDP binding | ISO GO_REF:0000119 | ACCEPT | Summary: GDP binding transferred from human ortholog. Reason: Core molecular function. |
| GO:0019076 viral release from host cell | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 endolysosomal function is co-opted during certain viral life cycles (e.g. HIV-1). Reason: Host-pathogen exploitation of Rab7 function rather than a primary biological role. |
| GO:0022615 protein to membrane docking | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 mediates docking of the retromer coat complex to endosomal membranes. Reason: Core function in retromer recruitment and cargo sorting. |
| GO:0030672 synaptic vesicle membrane | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 activity at synaptic vesicle membranes / presynaptic endosomes (ortholog transfer). Reason: Neuron-specific localization relevant to synaptic recycling and neuropathy. |
| GO:0030904 retromer complex | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 colocalizes with the retromer complex on endosomes (ortholog transfer). Reason: Core function; Rab7 recruits retromer for cargo sorting. |
| GO:0031267 small GTPase binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 can interact with other small GTPases in Rab cascade regulation. Reason: Secondary function; Rab7 primarily recruits dedicated effectors. |
| GO:0032935 sterol sensor activity | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 contributes to sterol sensing via the ORP1L complex (contributes_to qualifier). Reason: ORP1L carries the sterol-sensing domain; Rab7 scaffolds the complex rather than directly sensing sterol. |
| GO:0032991 protein-containing complex | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 forms complexes with multiple effectors (RILP, ORP1L, PLEKHM1, retromer, HOPS). Reason: Accurate, though general; specific complex memberships are also captured. |
| GO:0036466 synaptic vesicle recycling via endosome | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 involvement in synaptic vesicle recycling via endosomes (ortholog transfer). Reason: Neuron-specific process, not a ubiquitous Rab7 function. |
| GO:0042147 retrograde transport, endosome to Golgi | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7-dependent retromer recruitment drives endosome-to-Golgi retrograde transport (e.g. CI-M6PR). Reason: Core function downstream of retromer recruitment. |
| GO:0042632 cholesterol homeostasis | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7-ORP1L coordinates cholesterol sensing and late endosome positioning. Reason: Specialized function mediated by the ORP1L effector; not the primary degradative role. |
| GO:0045022 early endosome to late endosome transport | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 controls the Rab5-to-Rab7 conversion that matures early endosomes into late endosomes. Confirmed in vivo in mouse liver as a mediator of late endosomal maturation. Reason: Core function; loss of Rab7 perturbs endosomal maturation in vivo. Supporting Evidence: PMID:41814093 Loss of Rab7, a mediator of late endosomal maturation, increased LNP escape. |
| GO:0045335 phagocytic vesicle | ISO GO_REF:0000119 | ACCEPT | Summary: Phagocytic vesicle localization transferred from human ortholog. Reason: Consistent with the phagosome maturation function. |
| GO:0045453 bone resorption | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 is required for osteoclast ruffled-border function and bone resorption, directly demonstrated in mouse osteoclasts. Reason: Cell-type-specific physiological role; the ruffled border is a lysosome-related compartment dependent on Rab7-mediated trafficking. |
| GO:0045732 positive regulation of protein catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7-mediated endolysosomal and autophagic flux promotes protein degradation. Reason: Direct consequence of the core degradative trafficking function. |
| GO:0048524 positive regulation of viral process | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 endolysosomal function can be exploited to promote viral processes. Reason: Host-pathogen interaction rather than a primary biological role. |
| GO:0061462 protein localization to lysosome | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 directs protein cargo to the lysosome. Reason: Core function in lysosomal targeting. |
| GO:0090120 lysosome to ER cholesterol transport | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7-ORP1L complex regulates cholesterol transport from lysosomes to the ER. Reason: Specialized lipid-homeostasis function mediated by the ORP1L effector. |
| GO:0090383 phagosome acidification | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 regulates phagosomal acidification during maturation. Reason: Part of the core phagosome maturation function. |
| GO:0090385 phagosome-lysosome fusion | ISO GO_REF:0000119 | ACCEPT | Summary: Phagosome-lysosome fusion transferred from human ortholog. Reason: Core function in phagolysosome formation. |
| GO:0097208 alveolar lamellar body | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 localization to alveolar lamellar bodies (lysosome-related organelles of type II pneumocytes). Reason: Cell-type-specific localization. |
| GO:0098830 presynaptic endosome | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rab7 activity at presynaptic endosomes (ortholog transfer). Reason: Neuron-specific localization relevant to synaptic function. |
| GO:0099638 endosome to plasma membrane protein transport | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 can influence recycling of cargo to the plasma membrane. Reason: Secondary function; the primary Rab7 role is degradative trafficking. |
| GO:1903542 negative regulation of exosomal secretion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 can negatively regulate exosome secretion by directing MVBs toward lysosomal degradation. Reason: Context-dependent regulatory role affecting exosome biogenesis. |
| GO:1903543 positive regulation of exosomal secretion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Rab7 can also positively regulate exosome secretion in the syndecan-syntenin-ALIX pathway. Reason: Context-dependent; Rab7 has opposing effects on exosome release depending on pathway. |
| GO:1905394 retromer complex binding | ISO GO_REF:0000119 | ACCEPT | Summary: Rab7 recruits/binds the retromer complex on endosomes for cargo sorting. Reason: Core molecular function specifying the retromer interaction. |
| GO:0003924 GTPase activity | EXP PMID:16855591 TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by... | ACCEPT | Summary: Biochemical study of TBC-domain GAPs directly characterizing Rab7 GTP hydrolysis, including the intrinsic GTPase activity accelerated by GAPs. Reason: Core molecular function with direct experimental support. Supporting Evidence: PMID:16855591 TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. |
| GO:0005765 lysosomal membrane | EXP PMID:28063257 Genetic screen in Drosophila muscle identifies autophagy-med... | ACCEPT | Summary: Experimental localization of Rab7 to the lysosomal membrane in an autophagy screen; Rab7 is cited as the defining marker of late endosomes and lysosomes. Reason: Core localization, experimentally supported. Supporting Evidence: PMID:28063257 late endosomes (Rab7, Rab9), lysosomes (Rab7) and others |
| GO:0010008 endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Endosome membrane localization by sequence similarity to characterized orthologs. Reason: Core localization. |
| GO:0031410 cytoplasmic vesicle | EXP PMID:23179371 Charcot-Marie-Tooth type 2B disease-causing RAB7A mutant pro... | ACCEPT | Summary: Rab7 on cytoplasmic vesicles in a study of CMT2B mutant interaction with peripherin; the paper notes Rab7a localizes to late endosomes and controls transport to late endosomes/lysosomes and maturation of phagosomes and autophagosomes. Reason: Accurate, though general; consistent with vesicular Rab7 localization. Supporting Evidence: PMID:23179371 RAB7A is localized to late endosomes and controls transport to late endosomes and lysosomes as well as maturation of phagosomes and autophagosomes |
| GO:0031902 late endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Late endosome membrane localization by sequence similarity. Reason: Core localization. |
| GO:0031966 mitochondrial membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial membrane association by sequence similarity (mitophagy / contact-site context). Reason: Context-dependent localization. |
| GO:0033162 melanosome membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Melanosome membrane localization by sequence similarity. Reason: Cell-type-specific (melanocyte) localization. |
| GO:0003925 G protein activity | IDA PMID:16855591 TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by... | ACCEPT | Summary: Direct demonstration of Rab7 nucleotide-dependent G protein behavior in the GAP study. Reason: Core molecular function, directly supported. Supporting Evidence: PMID:16855591 TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. |
| GO:0005515 protein binding | IPI PMID:38744829 RUFY4 deletion prevents pathological bone loss by blocking e... | REMOVE | Summary: Interaction between Rab7 and the effector RUFY4 in osteoclasts. Reason: GO:0005515 protein binding is uninformative. RUFY4 is a characterized Rab7 effector for autophagy/lysosome tethering; the functional role is captured by trafficking terms. Supporting Evidence: PMID:38744829 Recent studies have shown that RUFY4 is an effector of small GTPases such as Rab7 |
| GO:0098943 neurotransmitter receptor transport, postsynaptic endosome to lysosome | IDA PMID:24217640 Stargazin regulates AMPA receptor trafficking through adapto... | KEEP AS NON CORE | Summary: SynGO annotation associating Rab7 with postsynaptic endosome-to-lysosome AMPA-receptor trafficking during long-term depression. Reason: Revisited in the human/mouse Deliverome comparison. The accessible PMID text supports AMPA-receptor movement into late endosomal/lysosomal compartments during LTD, which is compatible with Rab7's conserved endosome-to-lysosome role. However, the paper emphasizes stargazin/AP-2/AP-3A rather than a Rab7-specific perturbation, so this should be retained only as a SynGO neuronal-context annotation and not treated as core Rab7 biology. Supporting Evidence: PMID:24217640 stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors |
| GO:0098943 neurotransmitter receptor transport, postsynaptic endosome to lysosome | IMP PMID:24217640 Stargazin regulates AMPA receptor trafficking through adapto... | KEEP AS NON CORE | Summary: SynGO IMP annotation for Rab7 in AMPA-receptor degradative trafficking during LTD. Reason: Revisited in the human/mouse Deliverome comparison. The PMID supports activity-dependent AMPA-receptor routing from early endosomes toward late endosomes/lysosomes, a route Rab7 generally controls. Because the accessible text identifies stargazin/AP-2/AP-3A as the experimental focus and does not give Rab7-specific mechanistic evidence, retain this as non-core and indirect. Supporting Evidence: PMID:24217640 transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes |
| GO:0098978 glutamatergic synapse | IDA PMID:24217640 Stargazin regulates AMPA receptor trafficking through adapto... | KEEP AS NON CORE | Summary: SynGO annotation placing Rab7 at glutamatergic synapses in AMPA-receptor trafficking. Reason: The source is a hippocampal LTD/AMPAR-trafficking study, so the glutamatergic-synapse context is biologically plausible for the SynGO annotation. It is not a core Rab7 localization, and the accessible text does not provide direct Rab7 localization or perturbation evidence, so retain only as a context-specific neuronal annotation. Supporting Evidence: PMID:24217640 necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons |
| GO:0098978 glutamatergic synapse | IMP PMID:24217640 Stargazin regulates AMPA receptor trafficking through adapto... | KEEP AS NON CORE | Summary: SynGO IMP annotation for Rab7 functional role at glutamatergic synapses (LTD). Reason: The PMID supports postsynaptic AMPA-receptor trafficking during LTD in hippocampal neurons, but the accessible text centers on stargazin and adaptor complexes rather than Rab7-specific evidence. Retain the SynGO row as a non-core neuronal-context annotation and avoid using it as a primary assertion about Rab7 function. Supporting Evidence: PMID:24217640 postsynaptic AMPA receptor trafficking mediates LTD |
| GO:0005770 late endosome | IDA PMID:35353806 TMED2 binding restricts SMO to the ER and Golgi compartments... | ACCEPT | Summary: Rab7 on late endosomes in a study of TMED2/SMO trafficking, by super-resolution 3D-STORM imaging. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:35353806 Dual color 3D-STORM analysis showing ERP72 (C), RCAS1 (D) and RAB7 (E) distribution |
| GO:0005765 lysosomal membrane | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | ACCEPT | Summary: Rab7 colocalizes with lysosomal membranes during autolysosomal lipid degradation in adipocytes. Reason: Core localization, experimentally supported in mouse. Supporting Evidence: PMID:23708524 RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells. |
| GO:0005829 cytosol | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | ACCEPT | Summary: Inactive GDP-bound Rab7 is cytosolic; observed in the lipolysis/lipophagy study. Reason: Consistent with the GTPase cycle (cytosolic GDP-bound pool). The cached text of PMID:23708524 does not include the localization panels, but the cytosolic GDP-bound pool is standard Rab GTPase biology. Supporting Evidence: file:mouse/Rab7/Rab7-notes.md It cycles between an inactive GDP-bound (cytosolic) state and an active GTP-bound (membrane-associated) state. |
| GO:0005515 protein binding | IPI PMID:29712939 Essential Role of the a3 Isoform of V-ATPase in Secretory Ly... | REMOVE | Summary: Interaction supporting V-ATPase a3-dependent Rab7 recruitment to secretory lysosomes. Reason: GO:0005515 protein binding is uninformative; the functional relationship is captured by recruitment/localization terms. Supporting Evidence: PMID:29712939 Rab7, a small GTPase involved in organelle trafficking. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial association by sequence similarity (mitophagy context). Reason: Context-dependent localization, not constitutive. |
| GO:0099638 endosome to plasma membrane protein transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rab7 influence on plasma-membrane-directed cargo transport by sequence similarity. Reason: Secondary function relative to the core degradative role. |
| GO:0005770 late endosome | IDA PMID:27390154 Loss of strumpellin in the melanocytic lineage impairs the W... | ACCEPT | Summary: Rab7 used as the late endosomal marker in a melanocyte WASH/strumpellin colocalization study. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:27390154 a significant increase in the colocalization of WASH and the late endosomal marker Rab7 |
| GO:0005764 lysosome | IDA PMID:29712939 Essential Role of the a3 Isoform of V-ATPase in Secretory Ly... | ACCEPT | Summary: Active Rab7 functions on (secretory) lysosomes, recruited in a V-ATPase a3-dependent manner. Reason: Core site of action, experimentally supported in mouse. Supporting Evidence: PMID:29712939 Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment. |
| GO:0051650 establishment of vesicle localization | IMP PMID:29712939 Essential Role of the a3 Isoform of V-ATPase in Secretory Ly... | ACCEPT | Summary: Rab7 recruitment is required for proper trafficking/positioning of secretory lysosomes (V-ATPase a3-dependent). Reason: Consistent with the established Rab7 role in vesicle/organelle positioning. Supporting Evidence: PMID:29712939 Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment. |
| GO:0005770 late endosome | IDA PMID:25592972 An aberrant sugar modification of BACE1 blocks its lysosomal... | ACCEPT | Summary: Rab7 used as a late-endosome marker in subcellular fractionation in a study of BACE1 lysosomal targeting. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:25592972 immunoblotted for BACE1, APP, rab5, or rab7 |
| GO:0005515 protein binding | IPI PMID:27777970 PLEKHM1/DEF8/RAB7 complex regulates lysosome positioning and... | REMOVE | Summary: Rab7 binds the PLEKHM1/DEF8 lysosome-positioning effector complex. Reason: GO:0005515 protein binding is uninformative. PLEKHM1 is a well-characterized Rab7 effector; the function is captured by lysosome positioning/trafficking terms. Supporting Evidence: PMID:27777970 PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. |
| GO:0005768 endosome | IDA PMID:26582200 Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum... | ACCEPT | Summary: Rab7 on endosomes in a study of Lifeguard/Fas signaling. Reason: Accurate, though general; more specific late endosome terms are also annotated. |
| GO:0005811 lipid droplet | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | ACCEPT | Summary: Rab7 localizes to lipid droplets and the LD-associated pool drives their autophagic degradation during beta-adrenergic lipolysis in mouse adipocytes. Reason: Experimentally supported localization underpinning the lipophagy function. Supporting Evidence: PMID:23708524 ADRB2 stimulation has caused a marked increase in the autophagy-targeted LDs for lysosomal degradation, which is dependent on the LD-associated RAB7 |
| GO:0031902 late endosome membrane | IDA PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | ACCEPT | Summary: Rab7 on late endosome membranes in the adipocyte lipolysis/lipophagy study. Reason: Core localization, experimentally supported. Supporting Evidence: PMID:23708524 RAB7, being primarily associated with late endosomes, is a central factor in endosomal trafficking |
| GO:0061724 lipophagy | IMP PMID:23708524 Ξ²-adrenergic receptor-stimulated lipolysis requires the RAB7... | ACCEPT | Summary: Rab7 is required for autolysosome-mediated lipid-droplet degradation (lipophagy) in fat cells, shown by knockdown and dominant-negative mutant. Reason: Directly demonstrated mouse function; a specialized branch of the core autophagy role. Supporting Evidence: PMID:23708524 RAB7 plays a pivotal role in the regulation of this autolysosome-mediated lipid degradation in fat cells. |
| GO:0005770 late endosome | IDA PMID:24760869 In vivo regulation of NGF-mediated functions by Nedd4-2 ubiq... | ACCEPT | Summary: Rab7 on late endosomes in a study of Nedd4-2/TrkA trafficking. Reason: Core localization. The cached text of PMID:24760869 does not name Rab7 (marker usage is in figure panels), so the localization claim is corroborated from another cached study using Rab7 as the late endosomal marker. Supporting Evidence: PMID:15588329 the late endosomal marker, Rab7 |
| GO:0034045 phagophore assembly site membrane | IDA PMID:19956673 An initial step of GAS-containing autophagosome-like vacuole... | MODIFY | Summary: Rab7 is recruited to Atg5-positive early membranes during formation of GAS-containing autophagosome-like vacuoles (GcAVs), a xenophagy structure - not to the phagophore assembly site. Reason: The term is wrong in kind, not the localization. The cited paper reports Rab7 on GcAVs labelled by GFP-LC3 and, at the early phase, on GFP-Atg5- positive membranes in NIH3T3 and HeLa cells. It never examines the phagophore assembly site, and it explicitly excludes canonical autophagosome formation, in which Rab7 is dispensable. An Atg5-positive early sequestering membrane is a phagophore (GO:0061908), so that is the supported destination; GO:0034045 additionally asserts a bounding membrane that the PAS does not have (see modules/phagophore_assembly_site.yaml and GO issue #29437). Note this annotation is the source of the human RAB7A GO:0034045 IEA, projected via GO_REF:0000107, so the error propagates. Prior review of this annotation was ACCEPT on the non-specific ground that it was "consistent with the Rab7 role in autophagy", which does not distinguish the compartment. Proposed replacements: phagophore Supporting Evidence: PMID:19956673 Thus, a population of Rab7 is recruited to GFP-Atg5 positive membranes during the early phase of GcAV formation. PMID:19956673 Rab7 as an additional component, which is dispensable in canonical autophagosome formation |
| GO:0005770 late endosome | IDA PMID:24334765 The tumor susceptibility gene TMEM127 is mutated in renal ce... | ACCEPT | Summary: Rab7 on late endosomes in a study of TMEM127 endolysosomal function. Reason: Core localization. The cached text of PMID:24334765 does not name Rab7 (marker usage is in figure panels), so the localization claim is corroborated from another cached study using Rab7 as the late endosomal marker. Supporting Evidence: PMID:15588329 the late endosomal marker, Rab7 |
| GO:0005515 protein binding | IPI PMID:22467241 V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differe... | REMOVE | Summary: Rab7 interaction in the context of ATP6AP1/Ac45 and osteoclast lysosomal trafficking. Reason: GO:0005515 protein binding is uninformative; the relevant function is lysosomal trafficking in osteoclasts. |
| GO:0005770 late endosome | IDA PMID:24035762 Christianson syndrome protein NHE6 modulates TrkB endosomal ... | ACCEPT | Summary: Rab7 used as a late-endosome marker (co-staining with NHE6) in a study of TrkB endosomal signaling. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:24035762 Rab7-associated endosomes (late endosomes) |
| GO:0005515 protein binding | IPI PMID:24549040 C9ORF72, implicated in amytrophic lateral sclerosis and fron... | REMOVE | Summary: Rab7 interaction in the context of C9ORF72 endosomal trafficking. Reason: GO:0005515 protein binding is uninformative; C9ORF72 regulates Rab-mediated endosomal trafficking, captured by trafficking terms. |
| GO:0005515 protein binding | IPI PMID:22275436 Melanoregulin regulates retrograde melanosome transport thro... | REMOVE | Summary: Rab7 interaction in melanoregulin/RILP-p150Glued retrograde melanosome transport. Reason: GO:0005515 protein binding is uninformative; the RILP effector axis is captured by trafficking/transport terms. |
| GO:0005770 late endosome | IDA PMID:23028046 Cellular adaptation to anthrax lethal toxin-induced mitochon... | ACCEPT | Summary: Rab7 on late endosomes in a macrophage anthrax-toxin/MLN64 study. Reason: Core localization, experimentally observed. |
| GO:0005737 cytoplasm | IDA PMID:18656450 Trafficking of cGMP-dependent protein kinase II via interact... | ACCEPT | Summary: Cytoplasmic localization observed in a cGKII/Rab11 trafficking study. Reason: Accurate but general; the cytosol and specific vesicular compartments are more informative and also annotated. |
| GO:0045335 phagocytic vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: Phagocytic vesicle localization by sequence similarity. Reason: Consistent with the phagosome maturation function. |
| GO:0090383 phagosome acidification | ISS GO_REF:0000024 | ACCEPT | Summary: Phagosome acidification by sequence similarity. Reason: Part of the core phagosome maturation function. |
| GO:0090385 phagosome-lysosome fusion | ISS GO_REF:0000024 | ACCEPT | Summary: Phagosome-lysosome fusion by sequence similarity. Reason: Core function in phagolysosome formation. |
| GO:0005515 protein binding | IPI PMID:19368996 The drs tumor suppressor is involved in the maturation proce... | REMOVE | Summary: Rab7 interaction in a study of the drs tumor suppressor in autophagy maturation. Reason: GO:0005515 protein binding is uninformative; the autophagy maturation role is captured by autophagy terms. |
| GO:0005770 late endosome | IDA PMID:19509052 Derlin-dependent accumulation of integral membrane proteins ... | ACCEPT | Summary: Rab7 on late endosomes in a Derlin membrane-protein accumulation study. Reason: Core localization, experimentally observed. |
| GO:0045022 early endosome to late endosome transport | ISS GO_REF:0000024 | ACCEPT | Summary: Early-to-late endosome transport by sequence similarity (Rab5-to-Rab7 conversion). Reason: Core function in endosomal maturation. |
| GO:0005770 late endosome | IDA PMID:20943658 Expression, localization, and biochemical characterization o... | ACCEPT | Summary: Rab7 marks the late endosomes to which Nmnat2 localizes. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:20943658 Nmnat2 localizes to Rab7-containing late endosomes |
| GO:0005515 protein binding | IPI PMID:12972561 Rabring7, a novel Rab7 target protein with a RING finger mot... | REMOVE | Summary: Identification of Rabring7 (BCA2/RNF115) as a Rab7 target protein with a RING finger motif. Reason: GO:0005515 protein binding is uninformative; this is a specific effector interaction whose function is better captured by other terms. |
| GO:0005770 late endosome | IDA PMID:15588329 Membrane trafficking and mitochondrial abnormalities precede... | ACCEPT | Summary: Rab7 used as the late endosomal marker in a juvenile neuronal ceroid lipofuscinosis cerebellar cell model. Reason: Core localization, experimentally observed. Supporting Evidence: PMID:15588329 the late endosomal marker, Rab7 |
| GO:0005764 lysosome | ISO PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi... | ACCEPT | Summary: Lysosome localization transferred from the retromer ortholog study, where the retromer subunit VPS26 colocalizes with Rab7. Reason: Core localization. Supporting Evidence: PMID:15078902 modest colocalization between mVPS26 and GFP-rab7 |
| GO:0005770 late endosome | ISO PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi... | ACCEPT | Summary: Late endosome localization transferred from the retromer ortholog study, where the retromer subunit VPS26 colocalizes with Rab7. Reason: Core localization. Supporting Evidence: PMID:15078902 modest colocalization between mVPS26 and GFP-rab7 |
| GO:0005770 late endosome | IDA PMID:11172003 A FYVE-finger-containing protein, Rabip4, is a Rab4 effector... | ACCEPT | Summary: Rab7 on late endosomes in a study of the Rab4 effector Rabip4. Reason: Core localization, experimentally observed. |
| GO:0006886 intracellular protein transport | TAS PMID:11042173 Proteomics characterization of abundant Golgi membrane prote... | KEEP AS NON CORE | Summary: Rab7 general role in intracellular protein transport, from a Golgi membrane proteomics paper. Reason: Too general; the specific endosome-to-lysosome and retrograde transport terms capture the actual function more precisely. |
| GO:0005794 Golgi apparatus | IDA PMID:11042173 Proteomics characterization of abundant Golgi membrane prote... | MARK AS OVER ANNOTATED | Summary: Rab7 detected in a bulk proteomic characterization of abundant Golgi membrane proteins. Reason: Rab7 is a late-endosome/lysosome GTPase; detection in a Golgi membrane fraction most plausibly reflects co-fractionation/contamination or transient retrograde-pathway association rather than a genuine steady-state Golgi pool. Not a core localization. |
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Download this section (compressed HTML)Q: The Nature Biotechnology study (PMID:41814093) shows that loss of Rab7 increases cytosolic escape of lipid nanoparticles in mouse liver. Does Rab7 activity define a general, druggable checkpoint that partitions endocytosed cargo between degradation and cytosolic escape, and can transient Rab7 modulation be exploited to enhance therapeutic nucleic-acid delivery?
Q: How are the tissue-specialized Rab7 functions (adipocyte lipophagy, synaptic AMPA-receptor turnover, osteoclast ruffled-border trafficking) differentially wired through distinct effectors despite a single ubiquitous GTPase switch?
Experiment: Use the LysoTag/Lysosomal Barcoding in vivo endosomal-escape assay (PMID:41814093) across conditional Rab7 (Rab7a) knockout tissues to quantify, in a tissue-resolved manner, how Rab7 loss shifts the balance between lysosomal degradation and cytosolic escape of endocytosed cargo.
Experiment: Effector-interaction profiling (proximity labeling) of mouse Rab7 in adipocytes, neurons and osteoclasts to map the cell-type-specific effector modules that route the common Rab7 switch to lipophagy, synaptic receptor degradation and ruffled-border trafficking, respectively.
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