RAB7A is a small GTPase (EC 3.6.5.2) of the Rab family that serves as a master regulator of late endocytic trafficking, autophagy, and lysosomal biogenesis. It functions as a molecular switch cycling between inactive GDP-bound (cytosolic) and active GTP-bound (membrane-associated) states. When active, RAB7A localizes to late endosomes, lysosomes, autophagosomes, and phagosomes where it recruits effector proteins (RILP, FYCO1, HOPS, retromer) to control vesicle maturation, transport, tethering, and fusion. RAB7A is activated by the Mon1-Ccz1 guanine nucleotide exchange factor (GEF) and inactivated by TBC-domain GTPase-activating proteins (GAPs) including TBC1D5 and TBC1D15. The protein governs the critical Rab5-to-Rab7 endosomal maturation transition, late endosome-lysosome fusion, autophagosome-lysosome fusion, phagosome maturation, and retrograde transport. Mutations in RAB7A cause Charcot-Marie-Tooth type 2B (CMT2B) neuropathy through dysregulated nucleotide exchange and inappropriate activation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: RAB7A is a well-established lysosomal marker. UniProt states "Lysosome membrane" with multiple experimental evidence codes. The deep research confirms RAB7A "localizes primarily to acidic, pre-degradative and degradative organelles such as late endosomes, lysosomes" (PMID:20028791). Reason: Core localization for RAB7A function. This is the primary site where RAB7A exerts its regulatory function in vesicle fusion and cargo degradation. Confirmed by extensive experimental data and phylogenetic conservation. Supporting Evidence: PMID:20028791 Rab7 localizes primarily to acidic, pre-degradative and degradative organelles such as late endosomes, lysosomes, multivesicular bodies, phagosomes, autophagosomes and autophagolysosomes file:human/RAB7A/RAB7A-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0045335 phagocytic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: RAB7A is recruited to phagosomes and regulates phagosome maturation. PMID:21255211 demonstrates RAB7A localization to phagosomes containing S. aureus and M. tuberculosis. Reason: Core function in phagosome maturation pathway. RAB7A recruitment to phagosomes is essential for phagolysosome fusion and pathogen degradation. Supporting Evidence: PMID:21255211 Rab7, Rab20 and Rab39 regulated phagosomal acidification and Rab7, Rab20, Rab22b, Rab32, Rab34, Rab38 and Rab43 controlled the recruitment of cathepsin D to the phagosome |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Late endosome is the canonical localization for RAB7A. This is where RAB7A becomes activated by Mon1-Ccz1 GEF during Rab5-to-Rab7 conversion and controls endosomal maturation. Reason: Canonical localization site. RAB7A is the defining marker of late endosomes and controls the transition from early to late endosomal compartments. Supporting Evidence: PMID:20028791 Rab7 localizes primarily to acidic, pre-degradative and degradative organelles such as late endosomes, lysosomes |
| GO:0008333 endosome to lysosome transport | IBA GO_REF:0000033 | ACCEPT | Summary: This is the core biological process for RAB7A. It controls the maturation of late endosomes and their fusion with lysosomes for cargo degradation. Reason: Core biological function. RAB7A-mediated endosome-to-lysosome transport is essential for degradation of internalized receptors (e.g., EGFR) and other endocytic cargo. Supporting Evidence: PMID:20028791 Rab7 specifically controls the transition of early endosomes into the late-endosomal/lysosomal system and subsequent degradation of cargos associated with target vesicles |
| GO:0090385 phagosome-lysosome fusion | IBA GO_REF:0000033 | ACCEPT | Summary: RAB7A is required for phagosome-lysosome fusion. PMID:21255211 demonstrates that dominant-negative RAB7A blocks phagosome-lysosome fusion and phagosomal acidification. Reason: Core function in innate immunity. RAB7A-mediated phagolysosome fusion is critical for pathogen destruction. Supporting Evidence: PMID:21255211 The Rab GTPases responsible for phagosome maturation, phagosomal acidification and recruitment of cathepsin D were examined |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: RAB7A binds GTP and GDP nucleotides, which is the molecular basis of its function as a molecular switch. Reason: Too general. RAB7A specifically binds guanine nucleotides (GTP and GDP), which should be annotated separately for specificity. Proposed replacements: GTP binding GDP binding |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: RAB7A localizes to autophagosome membranes and is required for autophagosome-lysosome fusion. UniProt confirms "Cytoplasmic vesicle, autophagosome membrane" localization. Reason: Core localization for RAB7A role in autophagy. RAB7A on autophagosomes recruits effectors like FYCO1 and facilitates autolysosome formation. Supporting Evidence: PMID:20028791 fusion of autophagic vacuoles with lysosomes requires Rab7 activity |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: RAB7A has intrinsic GTPase activity (EC 3.6.5.2) that hydrolyzes GTP to GDP. This activity is accelerated by GAP proteins and is essential for the RAB7A activity cycle. Reason: Core molecular function. GTPase activity is fundamental to RAB7A function as a molecular switch controlling membrane trafficking. Supporting Evidence: PMID:20028791 when GTP is in constant supply (as is the case in vivo), catalytic activity in disease mutants is not significantly impaired |
| GO:0003925 G protein activity | IEA GO_REF:0000120 | ACCEPT | Summary: RAB7A functions as a G protein, cycling between active GTP-bound and inactive GDP-bound states to regulate membrane trafficking. Reason: Accurate molecular function. RAB7A belongs to the Rab family of small GTPases that function as molecular switches. Supporting Evidence: PMID:20028791 Rab GTPases function as molecular switches by cycling between active, GTP-bound states in which they are reversibly associated with specific vesicular membranes and inactive, GDP-bound states |
| GO:0005525 GTP binding | IEA GO_REF:0000120 | ACCEPT | Summary: GTP binding is essential for RAB7A activation and membrane association. Crystal structures confirm GTP binding pocket with Mg2+ cofactor. Reason: Core molecular function. GTP binding activates RAB7A and enables effector recruitment. Supporting Evidence: PMID:20028791 The structure of full-length L129F Rab7 bound to the non-hydrolysable GTP analog GppNHp was solved to 2.8 Γ
by molecular replacement (MR) using wild-type Rab7 as a search model (Table 1) |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000120 | ACCEPT | Summary: RAB7A localizes to lysosomal membranes as a peripheral membrane protein on the cytoplasmic face. Reason: Core localization. RAB7A on lysosomal membranes coordinates fusion events and lysosome positioning. Supporting Evidence: PMID:20028791 Rab7 localizes primarily to acidic, pre-degradative and degradative organelles such as late endosomes, lysosomes |
| GO:0005811 lipid droplet | IEA GO_REF:0000120 | ACCEPT | Summary: RAB7A localizes to lipid droplets, particularly during ADRB2-stimulated lipolysis through lipophagy. ISS evidence from mouse ortholog. Reason: Valid localization related to lipophagy function. RAB7A recruitment to lipid droplets facilitates their autophagic degradation. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: RAB7A participates in lipid metabolism through its role in lipophagy and cholesterol transport. Reason: Too general. RAB7A role in lipid metabolism is specifically through lipophagy and lysosome-to-ER cholesterol transport. Proposed replacements: lipophagy lysosome to ER cholesterol transport |
| GO:0006914 autophagy | IEA GO_REF:0000043 | ACCEPT | Summary: RAB7A is essential for autophagy, specifically autophagosome-lysosome fusion. Reason: Core biological function. RAB7A regulates the late stages of autophagy including autophagosome maturation and autolysosome formation. Supporting Evidence: PMID:20028791 fusion of autophagic vacuoles with lysosomes requires Rab7 activity |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: RAB7A localizes to endosome membranes, primarily late endosome membranes. Reason: Accurate localization. More specific term (late endosome membrane) is also annotated, but this parent term is appropriate for IEA evidence. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: RAB7A regulates protein transport through the endolysosomal system. Reason: Too general. RAB7A specifically regulates vesicular trafficking in the endolysosomal and autophagic pathways. More specific terms are annotated. |
| GO:0016042 lipid catabolic process | IEA GO_REF:0000043 | ACCEPT | Summary: RAB7A participates in lipid catabolism through lipophagy. Reason: Valid annotation through RAB7A role in lipophagy, which delivers lipid droplets to lysosomes for degradation. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: RAB7A has GTPase activity which is a type of hydrolase activity. Reason: Too general. The specific hydrolase activity is GTPase activity (GO:0003924), which is already annotated. Proposed replacements: GTPase activity |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: RAB7A localizes to phagosomal membranes during phagosome maturation. Reason: Core localization for innate immunity function. RAB7A on phagosome membranes coordinates maturation and fusion with lysosomes. Supporting Evidence: PMID:21255211 Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: RAB7A localizes to multiple types of cytoplasmic vesicles. Reason: Accurate but general. More specific vesicle type annotations are also present. |
| GO:0031902 late endosome membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Late endosome membrane is the canonical localization for active RAB7A. Reason: Core localization. This is where RAB7A is activated and recruits effectors for endosomal maturation and transport. Supporting Evidence: PMID:20028791 Rab7 localizes primarily to acidic, pre-degradative and degradative organelles such as late endosomes |
| GO:0031966 mitochondrial membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: RAB7A can be recruited to mitochondrial membranes during mitophagy. PMID:34432599 shows RIMOC1-dependent recruitment to damaged mitochondria. Reason: Context-dependent localization during mitophagy rather than constitutive localization. Important for specialized autophagy pathway. |
| GO:0033162 melanosome membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: RAB7A localizes to melanosome membranes. Melanosomes are lysosome-related organelles and RAB7A participates in their biogenesis. Reason: Cell-type specific localization relevant to melanocyte biology. Part of RAB7A role in lysosome-related organelle biogenesis. |
| GO:0098588 bounding membrane of organelle | IEA GO_REF:0000117 | ACCEPT | Summary: RAB7A localizes to the bounding membranes of various organelles as a peripheral membrane protein. Reason: Accurate general localization consistent with RAB7A membrane association pattern. |
| GO:0005515 protein binding | IPI PMID:15933719 Structural basis for recruitment of RILP by small GTPase Rab... | REMOVE | Summary: This study demonstrates RAB7A interaction with RILP effector. The structure of RAB7A-RILP complex was solved. Reason: GO:0005515 is uninformative for annotation purposes. The RILP interaction represents RAB7A effector binding which is part of its core molecular function. Consider more specific effector binding terms if available. Supporting Evidence: PMID:15933719 Mar 31. Structural basis for recruitment of RILP by small GTPase Rab7. |
| GO:0005515 protein binding | IPI PMID:18787122 The Salmonella virulence protein SifA is a G protein antagon... | REMOVE | Summary: Study on Salmonella virulence protein SifA as a G protein antagonist interacting with RAB7A. Reason: GO:0005515 is uninformative. This represents host-pathogen interaction where bacterial effector targets RAB7A. Supporting Evidence: PMID:18787122 The Salmonella virulence protein SifA is a G protein antagonist. |
| GO:0005515 protein binding | IPI PMID:25500191 PLEKHM1 regulates Salmonella-containing vacuole biogenesis a... | REMOVE | Summary: PLEKHM1 interaction with RAB7A during Salmonella-containing vacuole biogenesis. Reason: GO:0005515 is uninformative. PLEKHM1 is a RAB7A effector involved in lysosome/phagosome fusion. Supporting Evidence: PMID:25500191 Epub 2014 Dec 11. PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: High-throughput interactome study identifying RAB7A protein interactions. Reason: GO:0005515 is uninformative. HTP study without specific functional context. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:27291868 Characterization of a Relatively Malignant Form of Osteopetr... | REMOVE | Summary: RAB7A interaction with PLEKHM1 in context of osteopetrosis. Reason: GO:0005515 is uninformative. PLEKHM1 is a characterized RAB7A effector. Supporting Evidence: PMID:27291868 Jul 13. Characterization of a Relatively Malignant Form of Osteopetrosis Caused by a Novel Mutation in the PLEKHM1 Gene. |
| GO:0005515 protein binding | IPI PMID:28325809 The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traff... | REMOVE | Summary: PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes, with RAB7A interaction demonstrated. Reason: GO:0005515 is uninformative. PLEKHM1-RAB7A interaction is well-characterized effector binding. Supporting Evidence: PMID:28325809 2017 Mar 21. The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to lysosomes. |
| GO:0005515 protein binding | IPI PMID:30323948 Regulation of the small GTPase Rab1 function by a bacterial ... | REMOVE | Summary: Study on bacterial glucosyltransferase regulation of Rab GTPases. Reason: GO:0005515 is uninformative. Host-pathogen interaction context. Supporting Evidence: PMID:30323948 Regulation of the small GTPase Rab1 function by a bacterial glucosyltransferase. |
| GO:0005515 protein binding | IPI PMID:30721249 Structural basis of human ORP1-Rab7 interaction for the late... | REMOVE | Summary: Structural basis of ORP1L-RAB7A interaction for late endosome/lysosome targeting. Reason: GO:0005515 is uninformative. ORP1L is a characterized RAB7A effector involved in cholesterol sensing. Supporting Evidence: PMID:30721249 eCollection 2019. Structural basis of human ORP1-Rab7 interaction for the late-endosome and lysosome targeting. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interactome mapping study for neurodegenerative disease proteins. Reason: GO:0005515 is uninformative. HTP interactome study. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33452816 The endolysosomal adaptor PLEKHM1 is a direct target for bot... | REMOVE | Summary: PLEKHM1 as target of mTOR and MAPK pathways interacting with RAB7A. Reason: GO:0005515 is uninformative. PLEKHM1 effector interaction. Supporting Evidence: PMID:33452816 Feb 28. The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways. |
| GO:0005515 protein binding | IPI PMID:33947832 The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosom... | REMOVE | Summary: SARS-CoV-2 ORF3a inhibits autophagosome-lysosome fusion, affecting RAB7A. Reason: GO:0005515 is uninformative. Viral protein interaction with RAB7A. Supporting Evidence: PMID:33947832 The SARS-CoV-2 protein ORF3a inhibits fusion of autophagosomes with lysosomes. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Dual proteome-scale network study of human interactome. Reason: GO:0005515 is uninformative. HTP interactome study. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005770 late endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Late endosome localization from Ensembl Compara ortholog transfer. Reason: Consistent with experimental evidence and IBA annotation for late endosome localization. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: RAB7A cycles between membrane-bound (active) and cytosolic (inactive) states. GDP-bound form is cytosolic. Reason: Accurate. Inactive GDP-bound RAB7A is cytosolic, bound by GDI proteins. Supporting Evidence: PMID:20028791 Rab GTPases function as molecular switches by cycling between active, GTP-bound states in which they are reversibly associated with specific vesicular membranes and inactive, GDP-bound states in which they are predominantly cytosolic |
| GO:0019003 GDP binding | IEA GO_REF:0000107 | ACCEPT | Summary: RAB7A binds GDP in its inactive state. GDP binding is essential for the GTPase cycle. Reason: Core molecular function. GDP-bound RAB7A is the inactive form sequestered in cytosol by GDI. Supporting Evidence: PMID:20028791 We found that Rab7 mutants have an increased rate of GTP dissociation relative to wild-type |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A localization to synaptic vesicle membrane from ortholog data. Reason: Neuron-specific localization. RAB7A role in synaptic vesicle recycling is relevant to CMT2B neuropathy pathogenesis. |
| GO:0031267 small GTPase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A can interact with other small GTPases in cascade regulation. Reason: Secondary function. RAB7A primarily recruits effectors rather than binding other GTPases as its main function. |
| GO:0034045 phagophore assembly site membrane | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl projection of the mouse Rab7a annotation, which rests on recruitment to Atg5-positive early membranes during xenophagy, not on localization to the phagophore assembly site. Reason: This IEA is projected (GO_REF:0000107, WITH UniProtKB:P51150) from the mouse Rab7a IDA whose source paper, PMID:19956673, reports Rab7 on GAS-containing autophagosome-like vacuoles and on GFP-Atg5-positive early membranes, and states that Rab7 is dispensable in canonical autophagosome formation. The projected term is therefore wrong at the source, and correcting the mouse annotation should carry through here. An Atg5-positive early sequestering membrane is a phagophore (GO:0061908). GO:0034045 additionally asserts a bounding membrane the PAS does not have; see GO issue #29437. Proposed replacements: phagophore |
| GO:0036466 synaptic vesicle recycling via endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A involvement in synaptic vesicle recycling from rat ortholog. Reason: Neuron-specific process. Relevant to CMT2B pathogenesis but not a ubiquitous RAB7A function. |
| GO:0045453 bone resorption | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A role in osteoclast ruffled border function and bone resorption. Reason: Cell-type specific function in osteoclasts. RAB7A is found in ruffled border which is a late endosomal-like compartment. |
| GO:0061724 lipophagy | IEA GO_REF:0000107 | ACCEPT | Summary: RAB7A participates in lipophagy, the autophagic degradation of lipid droplets. Reason: Valid function consistent with RAB7A role in autophagy and lipid droplet localization. |
| GO:0097208 alveolar lamellar body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A localization to alveolar lamellar bodies from ortholog data. Reason: Cell-type specific (type II pneumocytes). Lamellar bodies are lysosome-related organelles. |
| GO:0098830 presynaptic endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RAB7A localization to presynaptic endosomes from ortholog data. Reason: Neuron-specific localization. Relevant to CMT2B pathogenesis. |
| GO:0005764 lysosome | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based localization from Human Protein Atlas. Reason: Experimental confirmation of core localization. |
| GO:0042632 cholesterol homeostasis | IDA PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to cont... | ACCEPT | Summary: RAB7A participates in cholesterol sensing and transport from lysosomes. Study on ORP1L-RILP-RAB7A complex in cholesterol transport. Reason: Well-characterized function. RAB7A coordinates with ORP1L to sense cholesterol and regulate late endosome positioning and cholesterol efflux. Supporting Evidence: PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. |
| GO:0090120 lysosome to ER cholesterol transport | IDA PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to cont... | ACCEPT | Summary: RAB7A-ORP1L complex regulates cholesterol transport from lysosomes to ER. Reason: Specific function in lipid homeostasis mediated by RAB7A effector ORP1L. Supporting Evidence: PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. |
| GO:0010008 endosome membrane | IDA PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to cont... | ACCEPT | Summary: RAB7A localization to endosome membrane demonstrated experimentally. Reason: Core localization confirmed by direct experimental evidence. Supporting Evidence: PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. |
| GO:0032935 sterol sensor activity | IDA PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to cont... | KEEP AS NON CORE | Summary: RAB7A contributes to sterol sensing through ORP1L complex. The annotation uses "contributes_to" qualifier. Reason: RAB7A contributes to but is not the primary sterol sensor - ORP1L has the sterol-sensing domain. RAB7A scaffolds the complex. Supporting Evidence: PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. |
| GO:0032991 protein-containing complex | IDA PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to cont... | ACCEPT | Summary: RAB7A is part of protein complexes with effectors. Reason: Accurate. RAB7A forms complexes with multiple effector proteins (RILP, ORP1L, PLEKHM1, retromer components). Supporting Evidence: PMID:19564404 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning. |
| GO:0005515 protein binding | IPI PMID:37821429 C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediate... | REMOVE | Summary: C9orf72-catalyzed GTP loading study showing VPS39/VPS41 interactions. Reason: GO:0005515 is uninformative. VPS39/VPS41 are HOPS complex components that are characterized RAB7A effectors. Supporting Evidence: PMID:37821429 C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy. |
| GO:0003925 G protein activity | IDA PMID:20028791 Disease mutations in Rab7 result in unregulated nucleotide e... | ACCEPT | Summary: Direct experimental demonstration of RAB7A GTPase cycle and activity. Reason: Core molecular function confirmed by biochemical characterization including crystal structure and enzymatic assays. Supporting Evidence: PMID:20028791 We determined the crystal structure of GTP-bound L129F mutant Rab7 at 2.8 Γ
resolution revealing an alteration to the nucleotide binding pocket, but no impact on the catalytic region of Rab7 |
| GO:0005765 lysosomal membrane | IDA PMID:38538795 The HEAT repeat protein HPO-27 is a lysosome fission factor. | ACCEPT | Summary: RAB7A localization to lysosomal membrane in lysosome fission study. Reason: Recent experimental confirmation of core localization. Supporting Evidence: PMID:38538795 Mar 27. The HEAT repeat protein HPO-27 is a lysosome fission factor. |
| GO:0061462 protein localization to lysosome | IDA PMID:38538795 The HEAT repeat protein HPO-27 is a lysosome fission factor. | ACCEPT | Summary: RAB7A role in protein localization to lysosomes demonstrated in HPO-27 lysosome fission study. Reason: Core function in lysosomal targeting pathway. Supporting Evidence: PMID:38538795 Mar 27. The HEAT repeat protein HPO-27 is a lysosome fission factor. |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: Cytosolic localization of inactive RAB7A from mouse ortholog. Reason: Consistent with GTPase cycle - GDP-bound RAB7A is cytosolic. |
| GO:0009617 response to bacterium | IMP PMID:22042847 Proteolytic targeting of Rab29 by an effector protein distin... | ACCEPT | Summary: RAB7A involvement in response to Salmonella infection through phagosome maturation. Reason: Valid function. RAB7A regulates phagosome maturation for bacterial degradation. Supporting Evidence: PMID:22042847 Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella. |
| GO:0005515 protein binding | IPI PMID:34432599 C5orf51 is a component of the MON1-CCZ1 complex and controls... | REMOVE | Summary: C5orf51/RIMOC1 interaction with RAB7A during mitophagy. Reason: GO:0005515 is uninformative. RIMOC1 is an accessory component of MON1-CCZ1 GEF complex. Supporting Evidence: PMID:34432599 2021 Aug 25. C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy. |
| GO:0005739 mitochondrion | IDA PMID:34432599 C5orf51 is a component of the MON1-CCZ1 complex and controls... | KEEP AS NON CORE | Summary: RAB7A recruitment to damaged mitochondria during mitophagy in RIMOC1-dependent manner. Reason: Context-dependent localization during mitophagy. Not constitutive mitochondrial localization. Supporting Evidence: PMID:34432599 2021 Aug 25. C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy. |
| GO:0099638 endosome to plasma membrane protein transport | IMP PMID:33147445 Identification of Required Host Factors for SARS-CoV-2 Infec... | KEEP AS NON CORE | Summary: RAB7A role in ACE2 cell surface expression, relevant to SARS-CoV-2 infection. Reason: Specific function in receptor recycling pathway. Primary RAB7A function is degradative trafficking rather than recycling. Supporting Evidence: PMID:33147445 Oct 24. Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells. |
| GO:0005515 protein binding | IPI PMID:30709847 VPS13A is closely associated with mitochondria and is requir... | REMOVE | Summary: VPS13A interaction with RAB7A. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:30709847 VPS13A is closely associated with mitochondria and is required for efficient lysosomal degradation. |
| GO:0005515 protein binding | IPI PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | REMOVE | Summary: CLN3-Hook1-RAB7A interaction in Batten disease context. Reason: GO:0005515 is uninformative. CLN3 is involved in endosomal trafficking. Supporting Evidence: PMID:15471887 Oct 7. Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. |
| GO:0030670 phagocytic vesicle membrane | TAS Reactome:R-HSA-9636564 | ACCEPT | Summary: Reactome pathway annotation for RAB7A on phagosome membrane. Reason: Consistent with experimental evidence for phagosome localization. |
| GO:0005515 protein binding | IPI PMID:26416964 RUN and FYVE domain-containing protein 4 enhances autophagy ... | REMOVE | Summary: RUFY4 interaction with RAB7A. Reason: GO:0005515 is uninformative. RUFY4 is a RAB7A effector for autophagy and lysosome tethering. Supporting Evidence: PMID:26416964 RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome tethering in response to Interleukin-4. |
| GO:0005515 protein binding | IPI PMID:22431521 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) ... | REMOVE | Summary: CLN5 interaction with RAB7A in endosomal sorting. Reason: GO:0005515 is uninformative. CLN5 is involved in endosomal trafficking. Supporting Evidence: PMID:22431521 Mar 19. The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. |
| GO:0000045 autophagosome assembly | IMP PMID:19956673 An initial step of GAS-containing autophagosome-like vacuole... | ACCEPT | Summary: RAB7A requirement for initial step of GAS-containing autophagosome-like vacuole formation. Reason: Core autophagy function. RAB7A is required for autophagosome maturation. Supporting Evidence: PMID:19956673 2009 Nov 26. An initial step of GAS-containing autophagosome-like vacuoles formation requires Rab7. |
| GO:0010008 endosome membrane | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | ACCEPT | Summary: RAB7A localization affected by Parkin in endolysosomal pathway. Reason: Experimental confirmation of endosome membrane localization. Supporting Evidence: PMID:26911690 Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway. |
| GO:0005515 protein binding | IPI PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | REMOVE | Summary: RILP interaction with RAB7A in Parkin modulation study. Reason: GO:0005515 is uninformative. RILP is a canonical RAB7A effector. Supporting Evidence: PMID:26911690 Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway. |
| GO:1905366 negative regulation of intralumenal vesicle formation | TAS PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: RAB7A negatively regulates ILV formation affecting exosome biogenesis. Reason: Secondary regulatory function affecting exosome secretion pathway. Supporting Evidence: PMID:26911690 Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway. |
| GO:1903542 negative regulation of exosomal secretion | IMP PMID:26911690 Parkin Modulates Endosomal Organization and Function of the ... | KEEP AS NON CORE | Summary: RAB7A negatively regulates exosome secretion through its role in endolysosomal trafficking. Reason: Secondary function. Primary RAB7A role is promoting lysosomal degradation rather than exosome release. Supporting Evidence: PMID:26911690 Parkin Modulates Endosomal Organization and Function of the Endo-Lysosomal Pathway. |
| GO:1905394 retromer complex binding | IMP PMID:27385586 Parkinson Disease-linked Vps35 R524W Mutation Impairs the En... | ACCEPT | Summary: RAB7A binding to retromer complex in VPS35-linked Parkinson disease study. Reason: Core molecular function. RAB7A recruits retromer complex to endosomes for cargo sorting and retrograde transport. Supporting Evidence: PMID:19531583 Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 PMID:27385586 2016 Jul 6. Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces Ξ±-Synuclein Aggregation. |
| GO:0010008 endosome membrane | IDA PMID:22431521 The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) ... | ACCEPT | Summary: RAB7A localization to endosome membrane in CLN5 study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:22431521 Mar 19. The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-8877451 | ACCEPT | Summary: Reactome annotation for MON1:CCZ1 GEF exchanging nucleotide on RAB7 at lysosomal membrane. Reason: Core localization in Reactome pathway context. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877451 | ACCEPT | Summary: Reactome annotation for cytosolic GDP-bound RAB7A. Reason: Consistent with GTPase cycle for inactive form. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9636684 | ACCEPT | Summary: Reactome pathway for bacterial effector NdkA affecting RAB7A. Reason: Cytosolic localization consistent with GTPase cycle. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Reactome annotation for RAB7A in secretory granule exocytosis. Reason: Secondary localization during granule exocytosis. Not primary localization site for RAB7A. |
| GO:0030667 secretory granule membrane | TAS Reactome:R-HSA-6798743 | KEEP AS NON CORE | Summary: Reactome annotation for RAB7A in neutrophil degranulation. Reason: Cell-type specific localization (neutrophils). Secretory granules share features with lysosomes. |
| GO:0005811 lipid droplet | ISS GO_REF:0000024 | ACCEPT | Summary: Lipid droplet localization from mouse ortholog for lipophagy function. Reason: Consistent with RAB7A role in lipophagy. |
| GO:0031902 late endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Late endosome membrane localization from mouse ortholog. Reason: Core localization confirmed by ortholog data. |
| GO:0061724 lipophagy | ISS GO_REF:0000024 | ACCEPT | Summary: Lipophagy function from mouse ortholog data. Reason: Core autophagy-related function. |
| GO:0005770 late endosome | IDA PMID:17010938 RILP interacts with VPS22 and VPS36 of ESCRT-II and regulate... | ACCEPT | Summary: RAB7A localization to late endosomes in RILP-ESCRT-II study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:17010938 RILP interacts with VPS22 and VPS36 of ESCRT-II and regulates their membrane recruitment. |
| GO:0005515 protein binding | IPI PMID:24344282 A mechanism for retromer endosomal coat complex assembly wit... | REMOVE | Summary: RAB7A interaction with retromer complex components. Reason: GO:0005515 is uninformative. Retromer binding is captured by GO:1905394 retromer complex binding. Supporting Evidence: PMID:24344282 A mechanism for retromer endosomal coat complex assembly with cargo. |
| GO:0022615 protein to membrane docking | IDA PMID:24344282 A mechanism for retromer endosomal coat complex assembly wit... | ACCEPT | Summary: RAB7A role in retromer complex docking to endosomal membranes. Reason: Core function in retromer recruitment and cargo sorting. Supporting Evidence: PMID:24344282 A mechanism for retromer endosomal coat complex assembly with cargo. |
| GO:1903543 positive regulation of exosomal secretion | IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | KEEP AS NON CORE | Summary: RAB7A role in syndecan-syntenin-ALIX exosome biogenesis pathway. Reason: Context-dependent function. RAB7A can both positively and negatively regulate exosome secretion depending on pathway. Supporting Evidence: PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. |
| GO:0030904 retromer complex | IDA PMID:19531583 Membrane recruitment of the cargo-selective retromer subcomp... | ACCEPT | Summary: RAB7A colocalization with retromer complex. Uses "colocalizes_with" qualifier. Reason: Core function. RAB7A recruits and colocalizes with retromer for cargo sorting. Supporting Evidence: PMID:19531583 Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 |
| GO:0030904 retromer complex | IDA PMID:24344282 A mechanism for retromer endosomal coat complex assembly wit... | ACCEPT | Summary: RAB7A-retromer complex colocalization. Reason: Additional evidence for RAB7A-retromer association. Supporting Evidence: PMID:24344282 A mechanism for retromer endosomal coat complex assembly with cargo. |
| GO:0042147 retrograde transport, endosome to Golgi | IMP PMID:19531583 Membrane recruitment of the cargo-selective retromer subcomp... | ACCEPT | Summary: RAB7A catalyzes retromer recruitment for retrograde transport. Reason: Core function. RAB7A-dependent retromer recruitment is essential for endosome-to-Golgi transport of cargo like CI-M6PR. Supporting Evidence: PMID:19531583 Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5 |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: RAB7A detected in exosome proteomics study (prostatic secretions). Reason: HTP proteomics finding. RAB7A presence in exosomes is consistent with its role in MVB/late endosome biology. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: RAB7A in urinary exosome proteomics. Reason: HTP proteomics finding. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: RAB7A in B-cell exosome proteomics. Reason: HTP proteomics finding. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-2213248 | ACCEPT | Summary: Reactome MHC class II antigen presentation pathway. Reason: Core localization in Reactome pathway context. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-8854255 | ACCEPT | Summary: Reactome TBC1D2A GAP pathway. Reason: Core localization where GAPs regulate RAB7A. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-8854329 | ACCEPT | Summary: Reactome TBC1D15 GAP pathway. Reason: Core localization where GAPs regulate RAB7A. |
| GO:0045335 phagocytic vesicle | IDA PMID:21255211 Rab GTPases regulating phagosome maturation are differential... | ACCEPT | Summary: Direct observation of RAB7A on phagosomes containing S. aureus and M. tuberculosis. Reason: Core localization for innate immunity function experimentally confirmed. Supporting Evidence: PMID:21255211 We compared the localization of 42 distinct Rab GTPases to phagosomes containing either Staphylococcus aureus or M. tb |
| GO:0090383 phagosome acidification | IMP PMID:21255211 Rab GTPases regulating phagosome maturation are differential... | ACCEPT | Summary: RAB7A required for phagosome acidification shown by dominant-negative studies. Reason: Core function in phagosome maturation pathway. Supporting Evidence: PMID:21255211 Rab7, Rab20 and Rab39 regulated phagosomal acidification |
| GO:0090385 phagosome-lysosome fusion | IMP PMID:21255211 Rab GTPases regulating phagosome maturation are differential... | ACCEPT | Summary: RAB7A required for phagosome-lysosome fusion experimentally demonstrated. Reason: Core function. RAB7A on phagosomes mediates fusion with lysosomes for pathogen degradation. Supporting Evidence: PMID:21255211 2011 Feb 21. Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes. |
| GO:0006622 protein targeting to lysosome | IMP PMID:22115783 Lysosomal targeting of phafin1 mediated by Rab7 induces auto... | ACCEPT | Summary: RAB7A role in phafin1-mediated lysosomal targeting and autophagosome formation. Reason: Core function in lysosomal targeting pathway. Supporting Evidence: PMID:22115783 Lysosomal targeting of phafin1 mediated by Rab7 induces autophagosome formation. |
| GO:0005515 protein binding | IPI PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | REMOVE | Summary: CLN3 interaction with RAB7A affecting late endosomal compartment localization. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:22261744 Epub 2012 Jan 20. Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments. |
| GO:0015031 protein transport | TAS PMID:19392663 Rab7: roles in membrane trafficking and disease. | KEEP AS NON CORE | Summary: Review article on RAB7A roles in membrane trafficking. Reason: Too general. More specific transport processes are annotated. Supporting Evidence: PMID:19392663 Rab7 plays critical roles in the endocytic processes |
| GO:0090382 phagosome maturation | TAS PMID:19392663 Rab7: roles in membrane trafficking and disease. | ACCEPT | Summary: Review article describing RAB7A role in phagosome maturation. Reason: Core function in innate immunity supported by review. Supporting Evidence: PMID:19392663 Rab7 participates in multiple regulation mechanisms in endosomal sorting, biogenesis of lysosome |
| GO:0005515 protein binding | IPI PMID:14617358 Human VPS34 and p150 are Rab7 interacting partners. | REMOVE | Summary: VPS34-p150 complex interaction with RAB7A. Reason: GO:0005515 is uninformative. VPS34/PIK3C3 is a characterized RAB7A interacting partner involved in PI3P production. Supporting Evidence: PMID:14617358 Human VPS34 and p150 are Rab7 interacting partners. |
| GO:0005515 protein binding | IPI PMID:16176980 The oxysterol-binding protein homologue ORP1L interacts with... | REMOVE | Summary: ORP1L interaction with GTP-bound RAB7A. Reason: GO:0005515 is uninformative. ORP1L is a well-characterized RAB7A effector for cholesterol sensing. Supporting Evidence: PMID:16176980 2005 Sep 21. The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments. |
| GO:0005770 late endosome | IDA PMID:14617358 Human VPS34 and p150 are Rab7 interacting partners. | ACCEPT | Summary: RAB7A localization to late endosomes with VPS34/p150 complex. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:14617358 The hVPS34/p150 complex colocalized with rab7 on late endosomes |
| GO:0045022 early endosome to late endosome transport | IMP PMID:14617358 Human VPS34 and p150 are Rab7 interacting partners. | ACCEPT | Summary: RAB7A role in endosomal maturation from early to late endosomes. Reason: Core function. RAB7A controls the Rab5-to-Rab7 conversion during endosomal maturation. Supporting Evidence: PMID:14617358 Rab7 is required for late endosomal transport |
| GO:0019076 viral release from host cell | IMP PMID:22072966 Rab7A is required for efficient production of infectious HIV... | KEEP AS NON CORE | Summary: RAB7A required for HIV-1 production through endolysosomal pathway. Reason: Host-pathogen interaction function. RAB7A endolysosomal function is co-opted by HIV for viral assembly/release. Supporting Evidence: PMID:22072966 2011 Nov 3. Rab7A is required for efficient production of infectious HIV-1. |
| GO:0045732 positive regulation of protein catabolic process | IMP PMID:22072966 Rab7A is required for efficient production of infectious HIV... | ACCEPT | Summary: RAB7A promotes protein catabolism through lysosomal degradation. Reason: Core function. RAB7A-mediated endolysosomal and autophagic flux promotes protein degradation. Supporting Evidence: PMID:22072966 2011 Nov 3. Rab7A is required for efficient production of infectious HIV-1. |
| GO:0048524 positive regulation of viral process | IMP PMID:22072966 Rab7A is required for efficient production of infectious HIV... | KEEP AS NON CORE | Summary: RAB7A promotes HIV-1 infection through endolysosomal pathway. Reason: Host-pathogen interaction. Reflects viral exploitation of RAB7A function rather than primary biological role. Supporting Evidence: PMID:22072966 2011 Nov 3. Rab7A is required for efficient production of infectious HIV-1. |
| GO:0005515 protein binding | IPI PMID:20100911 FYCO1 is a Rab7 effector that binds to LC3 and PI3P to media... | REMOVE | Summary: FYCO1 effector interaction with RAB7A. Reason: GO:0005515 is uninformative. FYCO1 is a well-characterized RAB7A effector for plus-end directed transport. Supporting Evidence: PMID:20100911 FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport. |
| GO:0003924 GTPase activity | IDA PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: Direct biochemical characterization of RAB7A GTPase activity in CMT2B mutant study. Reason: Core molecular function confirmed by biochemical assays. Supporting Evidence: PMID:18272684 all three proteins exhibited higher nucleotide exchange rates and hydrolyzed GTP slower than the wild-type protein |
| GO:0005515 protein binding | IPI PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | REMOVE | Summary: RILP effector binding by RAB7A mutants. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:18272684 Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease. |
| GO:0005525 GTP binding | IDA PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: Direct demonstration of GTP binding by RAB7A. Reason: Core molecular function confirmed by nucleotide binding assays. Supporting Evidence: PMID:18272684 whereas 23% of overexpressed wild-type Rab7 was GTP bound in HeLa cells, the large majority of the mutant proteins (82-89%) were in the GTP-bound form |
| GO:0005764 lysosome | IDA PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: RAB7A localization to lysosomes in CMT2B study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:18272684 Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease. |
| GO:0005770 late endosome | IDA PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: RAB7A localization to late endosomes in CMT2B study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:18272684 Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease. |
| GO:0007174 epidermal growth factor catabolic process | IMP PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | KEEP AS NON CORE | Summary: RAB7A role in EGF receptor degradation through endolysosomal pathway. Reason: Specific example of RAB7A function in receptor downregulation. Core function is the general endosome-to-lysosome transport. Supporting Evidence: PMID:18272684 Functional characterization of Rab7 mutant proteins associated with Charcot-Marie-Tooth type 2B disease. |
| GO:0008333 endosome to lysosome transport | IMP PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: RAB7A requirement for endosome-to-lysosome transport demonstrated in CMT2B mutant study. Reason: Core biological function experimentally confirmed. Supporting Evidence: PMID:18272684 all three proteins exhibited higher nucleotide exchange rates and hydrolyzed GTP slower than the wild-type protein |
| GO:0019003 GDP binding | IDA PMID:18272684 Functional characterization of Rab7 mutant proteins associat... | ACCEPT | Summary: Direct demonstration of GDP binding by RAB7A in nucleotide dissociation assays. Reason: Core molecular function confirmed by nucleotide binding assays. Supporting Evidence: PMID:18272684 all three proteins exhibited higher nucleotide exchange rates and hydrolyzed GTP slower than the wild-type protein |
| GO:0005515 protein binding | IPI PMID:16925951 Novel RING E3 ubiquitin ligases in breast cancer. | REMOVE | Summary: RNF115 E3 ubiquitin ligase interaction with RAB7A. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:16925951 Novel RING E3 ubiquitin ligases in breast cancer. |
| GO:0005764 lysosome | IDA PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi... | ACCEPT | Summary: RAB7A localization to lysosomes in retromer study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. |
| GO:0005770 late endosome | IDA PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi... | ACCEPT | Summary: RAB7A localization to late endosomes in retromer study. Reason: Core localization experimentally confirmed. Supporting Evidence: PMID:15078902 Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. |
| GO:0003924 GTPase activity | TAS PMID:8954989 Molecular cloning and expression analysis of the human Rab7 ... | ACCEPT | Summary: Original cloning paper describing RAB7A as GTPase. Reason: Core molecular function from primary characterization. Supporting Evidence: PMID:8954989 Molecular cloning and expression analysis of the human Rab7 GTP-ase complementary deoxyribonucleic acid. |
| GO:0005770 late endosome | TAS PMID:2115402 Localization of low molecular weight GTP binding proteins to... | ACCEPT | Summary: Early study localizing Rab proteins to endocytic compartments. Reason: Core localization from early characterization studies. Supporting Evidence: PMID:2115402 Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. |
| GO:0006897 endocytosis | TAS PMID:2115402 Localization of low molecular weight GTP binding proteins to... | ACCEPT | Summary: RAB7A role in endocytic pathway from early localization study. Reason: General function in endocytic pathway. RAB7A specifically regulates late stages of endocytosis. Supporting Evidence: PMID:2115402 Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How do CMT2B mutations in RAB7A lead specifically to sensory neuron degeneration despite ubiquitous expression? CMT2B mutations cause increased nucleotide exchange and inappropriate activation rather than loss of function. Understanding the neuronal vulnerability could inform therapeutic strategies.
Q: What is the relative contribution of RAB7A to different autophagy pathways (macroautophagy, lipophagy, mitophagy)? RAB7A participates in multiple selective autophagy pathways but the specific mechanisms and relative importance may differ.
Experiment: Systematic comparison of RAB7A effector binding profiles in neurons vs. non-neuronal cells to understand CMT2B tissue specificity. This could reveal neuron-specific RAB7A functions that explain why CMT2B mutations cause peripheral neuropathy.
Experiment: Live imaging of RAB7A membrane cycling dynamics in patient-derived neurons carrying CMT2B mutations. Would directly test the hypothesis that dysregulated membrane cycling underlies neurodegeneration.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)