Affinage

RAB5A

Ras-related protein Rab-5A · UniProt P20339

Length
215 aa
Mass
23.7 kDa
Annotated
2026-06-10
100 papers in source corpus 56 papers cited in narrative 55 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB5A is a small GTPase that serves as the master regulator of early endosome biogenesis, tethering, and homotypic fusion, cycling between GTP- and GDP-bound states to control entry into the endocytic pathway (PMID:1900457, PMID:7890612). Its function depends on geranylgeranylation for membrane delivery and on a defined nucleotide cycle in which GTP-bound RAB5A is the active species (PMID:7890612); complete loss of all RAB5 isoforms abolishes early and late endosomes, collapses receptor-mediated and fluid-phase endocytosis, and is lethal, defining the pathway's dependence on RAB5 (PMID:34817057). Active RAB5A patterns endosomal membranes through a reconstituted GEF/effector handover from Rabex5 to Rabaptin5 that, together with RabGDI and PI(3)P, is sufficient to generate Rab5 membrane domains (PMID:32510320), and it recruits and allosterically activates the VPS34/VPS15 (PI3K complex II) lipid kinase by releasing the kinase domain over the bilayer to generate PI(3)P (PMID:33692360), which in turn recruits effectors such as EEA1 and SARA and engages a VPS34-TBC2 negative-feedback loop that enforces maturation directionality (PMID:12010460, PMID:12432064, PMID:28455411). RAB5A activity is set by an extensive regulatory network of Vps9-domain GEFs (Alsin/ALS2, RAP6) and TBC-domain GAPs (RN-tre, TBC1D17, TBC1D18), with GAP activity itself tuned by signaling kinases such as AMPK (PMID:15033976, PMID:16410077, PMID:11099046, PMID:34045668, PMID:36197338) and the protein further modulated by site-specific monoubiquitination at K140 and K165 that alters effector engagement and nucleotide handling, and by PKCε phosphorylation at Thr-7 (PMID:28968219, PMID:24872409). Through this machinery RAB5A drives internalization and signaling output of multiple surface receptors—EGFR, the insulin receptor/IRS1, TβRII, and TrkB—linking endocytosis to Raf-Erk, AKT-mTOR, and CREB-dependent transcriptional programs (PMID:11062256, PMID:15511088, PMID:32051546, PMID:16554017, PMID:32304339, PMID:32928890), and it governs phagosome and macropinosome maturation and the Rab5-to-Rab7 conversion that precedes lysosomal fusion (PMID:10206948, PMID:12640132, PMID:33722976). Beyond classical endocytosis, RAB5A executes ESCRT-dependent autophagosome closure and sequestration of damaged mitochondria, reversibly translocates to mitochondria under oxidative stress in an Alsin-dependent manner, drives focal-adhesion disassembly and integrin/MT1-MMP cycling to promote cell migration and invasion, and acts as the membrane anchor for the FERRY complex that delivers mRNAs and ribosomes to early endosomes (PMID:31010855, PMID:28134239, PMID:29469808, PMID:23813952, PMID:25049275, PMID:37267905, PMID:37267906).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1991 High

    Established RAB5 as a direct regulator of early endocytic membrane fusion, defining the founding activity of the protein.

    Evidence Cell-free endosome fusion assay with antibody inhibition and wild-type/dominant-negative overexpression

    PMID:1900457

    Open questions at the time
    • Did not resolve the nucleotide cycle kinetics
    • Effectors mediating fusion not yet identified
  2. 1995 High

    Showed that lipid prenylation is required for fusion activity and characterized the nucleotide-handling defects of key mutants, linking membrane targeting to GTPase function.

    Evidence In vitro fusion assay plus GTPase kinetics and nucleotide-binding analysis of Q79L and N133I mutants

    PMID:7890612

    Open questions at the time
    • Prenyltransferase and delivery machinery not addressed
    • Effector coupling unresolved
  3. 1998 High

    Placed RAB5 downstream of Ras-PKB/Akt signaling and revealed isoform-selective regulation of Rab5a by immune cytokines, connecting endocytosis to upstream signal transduction.

    Evidence Fluid-phase endocytosis and in vitro fusion assays with Akt constructs; IFN-γ induction with exchange and geranylgeranylation assays in macrophages

    PMID:9677351 PMID:9852039

    Open questions at the time
    • Direct molecular link between Akt and Rab5 GEFs not defined
    • Mechanism of isoform-selective transcription unknown
  4. 1999 High

    Defined RAB5A roles in phagosome maturation, recycling-pathway compartmentalization, and a PI3K-independent actin/migration function, broadening RAB5 beyond endosome fusion.

    Evidence Stable transfection and antisense knockdown phagosome assays; endosome immunoadsorption and EEA1 recruitment; microinjection of active Rab5 with cytoskeletal/migration readouts

    PMID:10206948 PMID:10512863 PMID:10574724

    Open questions at the time
    • Effectors for the migration function not identified at this stage
    • Rab5-to-Rab7 hand-off mechanism unresolved
  5. 2000 High

    Demonstrated isoform-specific Rab5a activation downstream of EGFR kinase and the Eps8/RN-tre GAP node, integrating receptor signaling with trafficking and Rac activation.

    Evidence GTP-Rab5a pulldowns with kinase-dead/truncated EGFR; reciprocal Co-IP and GAP assays linking Eps8, RN-tre and Rac; live-cell GFP-Rab5a imaging

    PMID:11062256 PMID:11073100 PMID:11099046

    Open questions at the time
    • GEF activating Rab5a downstream of EGFR not pinned
    • Quantitative dynamics of the activation/deactivation cycle unresolved
  6. 2002 Medium

    Defined the RAB5–VPS34/p150 PI(3)P axis and the FYVE effector SARA, establishing how active Rab5 generates the lipid signal that recruits downstream effectors.

    Evidence GTP-dependent binding and domain mapping to p150; subcellular fractionation; SARA epistasis with Rab5 mutants and transferrin recycling

    PMID:12010460 PMID:12432064

    Open questions at the time
    • Structural basis of VPS34 activation not yet resolved
    • Direct vs indirect recruitment of cytosolic kinase ambiguous
  7. 2003 High

    Placed RAB5 upstream of RAB7 in phagosome/endosome maturation and identified Rabip4' coordinating Rab4/Rab5 in recycling, articulating the conversion logic of the pathway.

    Evidence Dominant-negative Rab5/Rab7 with FRAP and PI3K inhibition; GTP-specific Rabip4' binding with transferrin recycling assays

    PMID:12640132 PMID:14617813

    Open questions at the time
    • Molecular machinery of Rab5-to-Rab7 conversion not defined here
    • GAP responsible for Rab5 inactivation unknown
  8. 2004 Medium

    Identified Alsin/ALS2 as a Vps9-domain GEF for Rab5 (and Rac1) and connected Rab5 to selective EGFR-Raf-Erk signaling and receptor surface availability.

    Evidence In vitro Vps9 GEF assays and localization; dominant-negative Rab5 effects on Erk vs JNK/p38 and on EGFR surface levels

    PMID:15033976 PMID:15260830 PMID:15511088

    Open questions at the time
    • How Alsin integrates Rab5 and Rac1 activation spatially unclear
    • Selectivity mechanism for Raf-Erk over other MAPKs not defined
  9. 2005 Medium

    Revealed pathogen subversion of Rab5a as a maturation checkpoint, with Listeria blocking Rab5a exchange and ADP-ribosylating Rab5a to escape killing.

    Evidence Rab5a mutant/Vps9 rescue of bacterial killing; mass-spec identification, Co-IP, and ADP-ribosylation/GEF/GDI assays

    PMID:15702993 PMID:18088303

    Open questions at the time
    • Host signaling that normally maintains Rab5a activity on phagosomes unresolved
    • Reversibility of ADP-ribosylation in vivo unknown
  10. 2006 Medium

    Expanded the GEF repertoire (RAP6) and established Rab5 control of insulin-receptor endocytosis and Erk/Akt signaling, linking trafficking to metabolic receptor output.

    Evidence In vitro GEF/RasGAP assays for RAP6; gain/loss-of-function Rab5 with insulin-stimulated kinase and endocytosis readouts

    PMID:16410077 PMID:16554017

    Open questions at the time
    • Direct Rab5–insulin receptor interaction not demonstrated here
    • Physiological GEF for insulin-induced Rab5 activation unknown
  11. 2007 Medium

    Connected Rab5 to neurodegenerative signaling, showing APP-BP1–Rab5 driven endosomal enlargement and apoptosis independent of Aβ.

    Evidence Co-IP with residue mapping; dominant-negative rescue of apoptosis; human AD tissue immunoblot correlation

    PMID:17611268

    Open questions at the time
    • Single-lab correlation with human tissue
    • Mechanism linking elevated Rab5 activity to apoptosis incomplete
  12. 2009 Medium

    Defined a Rab5-driven integrin internalization/recycling circuit downstream of caspase-8 promoting migration and metastasis in vivo.

    Evidence Rab5 activation, Co-IP with integrins/caspase-8, siRNA knockdown, integrin recycling and in vivo metastasis model

    PMID:19923319

    Open questions at the time
    • GEF activated by integrin/caspase-8 not identified
    • Direct vs indirect Rab5–integrin association unresolved
  13. 2011 Medium

    Captured spatial Rab5 activity dynamics at the leading edge and on macropinosomes, linking active Rab5 to focal-adhesion disassembly and organelle stability.

    Evidence Rab5 biosensor/FRET imaging, Co-IP with vinculin/paxillin, FAK dephosphorylation and invasion assays; macropinosome FRET with microtubule/pH perturbation

    PMID:21910808 PMID:23813952

    Open questions at the time
    • GAP/GEF setting leading-edge Rab5 cycling not defined
    • Mechanistic link from Rab5 to FAK Tyr397 dephosphorylation unclear
  14. 2014 Medium

    Broadened Rab5 functions to invadosome-driven invasion, autophagy regulation, meiotic spindle/kinetochore control, and PKCε-Thr7 phosphorylation governing migration.

    Evidence shRNA/mutant Rab5 invadosome and MT1-MMP trafficking assays in vivo; GTPase activity and autophagy assays; oocyte siRNA spindle phenotyping; PKCε Co-IP and phospho-mutant migration assays

    PMID:24872409 PMID:24876181 PMID:25049275 PMID:25483964

    Open questions at the time
    • Non-endocytic meiotic role mechanism only partly defined
    • How Thr-7 phosphorylation alters Rab5 nucleotide cycle unresolved
  15. 2015 Medium

    Identified Rab5 regulators of deactivation (DRG2-RabGAP5) and a Rab5-mediated VE-cadherin internalization pathway controlling endothelial barrier function.

    Evidence Co-IP and recycling/GTPase assays for DRG2; siRNA, activation assay and permeability assays in vitro and in vivo for VE-cadherin

    PMID:26112597 PMID:26582392

    Open questions at the time
    • DRG2 mechanism of promoting GAP action unresolved
    • Upstream signal coupling LPS to Rab5 activation unknown
  16. 2017 High

    Defined site-specific monoubiquitination as a regulatory layer and established Rab5-positive endosomes as an ESCRT-based route for damaged-mitochondria clearance.

    Evidence Ubiquitin co-transfection with K-to-R mutants, solution X-ray scattering and EGFR degradation assays; live imaging, EM, ESCRT/Parkin/Beclin1 manipulation

    PMID:28134239 PMID:28968219

    Open questions at the time
    • E3 ligases driving K140/K165 ubiquitination not identified
    • Relationship between endosomal and canonical mitophagy pathways unresolved
  17. 2018 High

    Established reversible, Alsin-dependent Rab5 translocation to mitochondria under oxidative stress, linking Rab5 regulation to ALS-relevant motor neuron vulnerability.

    Evidence Live imaging, fractionation, and oxidative-stress assays in Alsin-deficient iPSC-derived motor neurons

    PMID:29469808

    Open questions at the time
    • Mitochondrial receptor for translocated Rab5 unknown
    • Functional output of mitochondrial Rab5 not fully defined
  18. 2019 Medium

    Detailed Rab5 control of autophagosome closure via ESCRT, macropinosome sealing via lipid-phosphatase recruitment, and retrograde axonal transport of APPL1 signaling endosomes.

    Evidence ESCRT knockdown and Atg17-Snf7 Co-IP autophagosome-closure assays; SNARE/OCRL/Inpp5b/APPL1 knockdown with lipid biosensors; live imaging and FRET in hippocampal neurons

    PMID:30792402 PMID:31010855 PMID:33722976

    Open questions at the time
    • How Rab5 controls the Atg17–Snf7 interaction mechanistically unresolved
    • Adaptor coupling APPL1 endosomes to retrograde motors not defined
  19. 2020 High

    Resolved direct Rab5a–IRS1 binding driving IGF-AKT-mTOR signaling and muscle regeneration, plus Rab5 requirements for BDNF/TrkB nuclear signaling and Diaph1-TβRII trafficking.

    Evidence GTP-dependent Co-IP with residue mapping and conditional Rab5a knockout mice; dominant-negative Rab5 with Erk/CREB and reporter assays in neurons; Diaph1/TβRII Co-IP, activity and in vivo tumor assays

    PMID:32051546 PMID:32304339 PMID:32928890

    Open questions at the time
    • How GTP-Rab5a coordinates IRS1–IGFR assembly structurally unresolved
    • Generality of endosomal signal-to-nucleus relay across receptors not established
  20. 2021 High

    Provided structural and reconstitution mechanisms: cryo-ET of Rab5a activating VPS34 complex II, a minimal Rabex5/Rabaptin5 handover patterning system, AMPK-tuned TBC1D17 GAP control of GLUT trafficking, and the lethality of total Rab5 loss.

    Evidence Cryo-ET and liposome kinase assays; supported-bilayer reconstitution with purified components and TIRF; AMPK/TBC1D17 phospho-mutant GAP and GLUT4 assays; auxin-inducible triple knockout

    PMID:32510320 PMID:33692360 PMID:34045668 PMID:34817057

    Open questions at the time
    • In vivo recapitulation of the minimal patterning system not shown
    • Full set of physiological inputs tuning GAP/GEF balance incomplete
  21. 2022 Medium

    Identified TBC1D18 as a Mon1-associated Rab5-GAP whose loss causes Rab5 hyperactivation-driven maturation defects, clarifying how Rab5 inactivation enforces endosome conversion.

    Evidence Systematic TBC-RabGAP screen, Co-IP with Mon1, Mon1-KO rescue and cargo-degradation assays

    PMID:36197338

    Open questions at the time
    • Hierarchy among the multiple Rab5-GAPs in vivo unresolved
    • Coupling of TBC1D18 to Rab7 activation not fully defined
  22. 2023 High

    Defined the FERRY complex as a structural Rab5 effector that delivers mRNAs and ribosomes to early endosomes, establishing a non-canonical RNA-transport function.

    Evidence Cryo-EM structure, Rab5/mRNA pulldowns, interface mutagenesis and mRNA localization assays in cells and neurons

    PMID:37267905 PMID:37267906

    Open questions at the time
    • Physiological cargo mRNA selectivity rules incompletely defined
    • How endosomal mRNA delivery integrates with local translation unresolved
  23. 2024 Medium

    Linked Rab5a-mediated NET internalization to NF-κB inflammatory signaling and arthritis severity, extending Rab5 into innate immune cargo handling.

    Evidence siRNA and Rab5a knockout mice, NET-endosome co-localization, NF-κB pathway analysis, cytokine ELISA and arthritis scoring

    PMID:38485453

    Open questions at the time
    • Direct mechanism coupling endosomal NE to NF-κB unresolved
    • Single-lab in vivo model

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the dozen-plus GEFs, GAPs, and post-translational modifications are integrated to set spatiotemporal Rab5 activity for distinct functional outputs (endocytosis vs migration vs mitochondrial translocation vs mRNA transport) remains unresolved.
  • No unified model linking specific regulators to specific cellular outputs
  • Functional non-redundancy of Rab5a vs Rab5b/Rab5c isoforms incompletely mapped
  • In vivo physiological triggers for non-canonical functions largely undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 5 GO:0098772 molecular function regulator activity 5 GO:0060089 molecular transducer activity 4
Localization
GO:0005768 endosome 5 GO:0031410 cytoplasmic vesicle 4 GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3 R-HSA-9609507 Protein localization 1
Partners
ALSIN/ALS2APPL1EEA1IRS1RABAPTIN5RABEX5TBC1D17VPS34
Complex memberships
FERRY complexVPS34/VPS15 (PI3K complex II)

Evidence

Reading pass · 55 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Rab5 directly controls early endosome fusion in vitro: cytosol containing overexpressed wild-type Rab5 stimulated fusion, anti-Rab5 antibodies inhibited it, and the GTP-binding-defective mutant Rab5Ile133 inhibited fusion, establishing Rab5 as a regulator of early endocytic fusion. Cell-free endosome fusion assay, antibody inhibition, dominant-negative and wild-type overexpression Cell High 1900457
1995 Geranylgeranylation (lipid modification) of Rab5 is required for its ability to stimulate endosome fusion in vitro; unmodified Rab5 WT did not stimulate fusion. Biochemical characterization established that the Q79L mutant has reduced GTPase activity and slower GDP dissociation, while N133I cannot bind guanine nucleotides. In vitro endosome fusion assay, GTPase kinetics (single-step and steady-state), guanine nucleotide binding, trypsin protection assay The Journal of biological chemistry High 7890612
1994 Rab5a localizes to synaptic vesicles and early endosomes in both axonal and somatodendritic compartments of neurons; co-immunoisolation with synaptophysin-positive vesicles and electron microscopy after wild-type/mutant overexpression demonstrated a role for Rab5a in neuronal endocytosis and synaptic vesicle biogenesis. Immunofluorescence, co-immunoisolation, electron microscopy, overexpression of wild-type and mutant Rab5a in hippocampal neurons Neuron High 8043272
1996 Rab5:Q79L (GTPase-deficient mutant) stimulates early endosome fusion in vitro in an ATP-, NSF-, and phospholipase A2-dependent manner, demonstrating that downstream effectors including NSF and PLA2 act downstream of Rab5 activation. Cell-free endosome fusion assay, inhibitors (NEM, anti-NSF antibody, PLA2 inhibitors), electron microscopy Archives of biochemistry and biophysics High 8579373
1998 Ras activation of endocytosis requires both PKB/Akt and Rab5; constitutively active PKB/Akt stimulates endocytosis that is blocked by dominant-negative Rab5:N34, and active PKB/Akt is required for Rab5 (WT) to activate endosome fusion, placing Rab5 downstream of a Ras-PKB/Akt axis. Fluid-phase endocytosis assay (HRP uptake), dominant-negative and constitutively active constructs, in vitro endosome fusion reconstitution, PI3K inhibitors The Journal of biological chemistry High 9677351
1998 IFN-γ selectively induces Rab5a (but not Rab5b, Rab5c, Rab7, or Rab11) synthesis, membrane association in the GTP-bound form, and enhanced guanine nucleotide exchange in macrophages, indicating isoform-specific regulation of Rab5a by immune activation. Immunoprecipitation, Western blotting, in vitro geranylgeranylation assay, guanine nucleotide exchange assay, mRNA quantification The Journal of biological chemistry Medium 9852039
1999 Rab5a controls early phagosome–endosome interactions and phagosome maturation leading to phagosome–lysosome fusion in macrophages; overexpression accelerated Listeria monocytogenes degradation while antisense knockdown extended intraphagosomal survival. Rab5c had no effect. Stable transfection of Rab5a cDNA, antisense oligonucleotide knockdown, morphological (electron microscopy) and functional phagosome–lysosome fusion assay The Journal of biological chemistry High 10206948
1999 Rab5 activation induces lamellipodia formation and cell migration in fibroblasts through a mechanism independent of PI3K, Ras, Rac, Cdc42, or Rho, demonstrating a novel actin cytoskeleton regulatory role for Rab5 distinct from its endocytic function. Microinjection of active Rab5, dominant-negative constructs (Ras, Rac, Rho, Cdc42, PI3K inhibitors), actin/microtubule staining, migration assay Molecular biology of the cell Medium 10512863
1999 Rab5 and Rab11 define biochemically distinct endosomal compartments along the transferrin pathway; transferrin moves sequentially through Rab5-positive sorting endosomes then Rab11-positive recycling endosomes, and EEA1 is preferentially recruited to Rab5-positive endosomes. Immunoadsorption purification of endosomes, electron microscopy, in vitro EEA1 recruitment assay, transferrin trafficking assay Journal of cell science High 10574724
2000 EGF receptor activation induces rapid, transient activation of Rab5a (but not Rab5b or Rab5c) and promotes EEA1 translocation to membranes; EGF-stimulated endocytosis requires EGFR kinase activity and specific C-terminal tyrosine residues, placing Rab5a downstream of EGFR kinase signaling. GTP-Rab5a pulldown assay, dominant-negative (Rab5:N34) and truncation mutant expression, fluid-phase and receptor-mediated endocytosis assays, kinase-dead EGFR constructs The Journal of cell biology High 11062256
2000 Eps8 links EGFR signaling to Rab5-mediated trafficking: through its SH3 domain Eps8 interacts with RN-tre, a Rab5 GAP whose activity is regulated by EGFR. RN-tre inhibits EGFR internalization by acting on Rab5, and also diverts Eps8 from Rac activation, integrating signaling and trafficking. Co-immunoprecipitation, SH3 domain pulldown, Rab5 GTPase activity assay, endocytosis assay, Rac activation assay Nature High 11099046
2000 GFP-Rab5a activation (by H-ras:G12V or EGF) causes endosome enlargement, increased fusion, membrane ruffling, and pinosome formation in live fibroblasts; GFP-Rab5a is transiently recruited to nascent phagosomes in macrophages engulfing bacteria. Live-cell imaging with GFP-Rab5a, time-lapse microscopy, co-expression with constitutively active/dominant-negative mutants Journal of leukocyte biology Medium 11073100
2001 Rab5A-dependent endocytosis mediates internalization of exogenous α-synuclein into neurons; GTPase-deficient Rab5A (dominant-negative) reduced α-synuclein uptake and cytotoxicity, establishing Rab5A as the endocytic mediator of α-synuclein internalization and subsequent Lewy body-like inclusion formation. Cell viability assay, dominant-negative Rab5A expression, immunofluorescence of inclusion bodies, exogenous α-synuclein addition The Journal of biological chemistry Medium 11316809
2001 Rab5 can dimerize between isoforms (Rab5b and Rab5c) in a GTP-bound conformation-dependent manner; Arg81 in the Switch II region is essential for dimerization, as shown by chemical cross-linking in vitro and in vivo. Yeast two-hybrid, in vitro and in vivo chemical cross-linking, site-directed mutagenesis (R81A) International journal of molecular medicine Medium 11562778
2002 Rab5 recruits the hVps34/p150 PI 3-kinase complex to early endosomes in a GTP-dependent manner via binding to the HEAT and WD40 domains of p150; this is required for EEA1 targeting to endosomes. However, Rab5 does not recruit cytosolic hVps34/p150 to the particulate fraction directly. Co-localization with constitutively active Rab5, recombinant p150 domain overexpression, subcellular fractionation, GTP-dependent binding assay Traffic Medium 12010460
2002 SARA (a FYVE domain protein) acts downstream of Rab5 on early endosomes; SARA overexpression phenocopies constitutively active Rab5Q79L (endosomal enlargement, delayed transferrin recycling), and all SARA phenotypes are counteracted by dominant-negative Rab5S34N. Overexpression, dominant-negative Rab5 epistasis, transferrin recycling assay, immunofluorescence Journal of cell science Medium 12432064
2003 Rab5 is essential for recruitment of Rab7 to phagosomes and progression to phagolysosomes; PI3K inhibition prolongs Rab5 association with phagosomes (measured by FRAP and EEA1 binding) and blocks fusion with late endosomes/lysosomes, placing Rab5 upstream of Rab7 in phagosome maturation. Dominant-negative Rab5/Rab7 expression, PI3K inhibitors (wortmannin), FRAP, EEA1 binding assay, immunofluorescence Molecular and cellular biology High 12640132
2003 Rabip4' binds simultaneously to GTP-bound Rab4 and GTP-bound Rab5, colocalizes with both GTPases on early endosomes in a PI3P-dependent manner, and coordinates their activities to regulate transferrin internalization and recycling. Co-immunoprecipitation, GTP-specific binding assay, dominant-negative Rabip4', transferrin recycling assay, wortmannin treatment Molecular biology of the cell Medium 14617813
2004 Alsin (ALS2 gene product) contains a Vps9 domain that functions as a guanine nucleotide exchange factor for Rab5; alsin also acts as a GEF for Rac1, and it localizes together with Rab5 and Rac1 on punctate membrane structures in fibroblasts and neurons. Vps9 domain GEF activity assay (nucleotide exchange), immunofluorescence, subcellular fractionation, Co-IP The Journal of biological chemistry High 15033976
2004 Dominant-negative Rab5 (Rab5:S34N) selectively blocks EGF activation of the Raf-Erk1/2 pathway and EGF-stimulated DNA synthesis and cyclin D1 transcription without affecting JNK and p38 pathways, demonstrating Rab5 as a selective regulator of EGFR-Raf-Erk signaling. Dominant-negative and overexpression constructs, kinase assays (Erk1/2, JNK, p38), [3H]thymidine incorporation, cyclin D1 reporter European journal of cell biology Medium 15511088
2004 Constitutive expression of activated Rab5 (Q79L) causes ligand-independent internalization of EGFR from the cell surface into intracellular vesicles, reducing available cell-surface EGFR and diminishing EGF-stimulated signaling. Stable and transient expression of Rab5 mutants in HeLa cells, EGFR surface ELISA, immunofluorescence, EGF blocking antibody Traffic Medium 15260830
2005 Listeria monocytogenes inhibits Rab5a GDP/GTP exchange activity as its primary phagosomal survival mechanism; overexpression of constitutively active Rab5a:Q79L or its GEF Vps9 restores listericidal activity via cathepsin-D, while dominant-negative Rab5a:S34N increases bacterial survival. CHO cell transfection with Rab5a mutants, intracellular bacterial viability assay, Rab5a exchange activity assay, cathepsin-D inhibitor experiments Traffic Medium 15702993
2006 RAP6 (Rab5-activating protein 6) is a novel Rab5 GEF; its Vps9 domain is sufficient for interaction with GDP-bound Rab5 and catalyzes guanine nucleotide exchange; RAP6 also has RasGAP activity via a separate domain and its overexpression affects fluid-phase and receptor-mediated endocytosis. In vitro GEF activity assay, RasGAP activity assay, immunofluorescence, endocytosis assay Biochemical and biophysical research communications Medium 16410077
2007 Listeria GAPDH (p40/Lmo2459) binds Rab5a within the phagosomal membrane, causes Rab5a-specific ADP-ribosylation, and blocks Rab5a GEF (Vps9) and GDI interactions, thereby inhibiting Rab5a-mediated phagosome–endosome fusion. Protein identification by mass spectrometry, co-IP, ADP-ribosylation assay, Rab5a exchange factor and GDI functional assays Traffic Medium 18088303
2007 Rab5 mediates an APP/APP-BP1 signaling pathway leading to neuronal apoptosis: APP-BP1 binds Rab5 (residues 443–479), elevated Rab5 activity in early endosomes is detected in AD neurons and fibroblasts, and inhibition of Rab5 or dynamin rescues APP-induced apoptosis independently of Aβ production. Co-IP (APP-BP1/Rab5), dominant-negative Rab5/dynamin expression, neuronal apoptosis assay, endosome size measurement, postmortem tissue immunoblot The Journal of neuroscience Medium 17611268
2009 Rab5 activation downstream of integrin ligation and caspase-8 leads to β1 integrin internalization and recycling, Rac activation, and cell migration; Rab5 co-precipitates with integrins and caspase-8, and Rab5 knockdown abrogates caspase-8-mediated migration and metastasis in vivo. Rab5 activation assay, co-immunoprecipitation, siRNA knockdown, integrin recycling assay, in vivo metastasis model Molecular biology of the cell Medium 19923319
2010 Drosophila Rab5 directly interacts with the heterotrimeric G protein Gαo as purified proteins; Gαo leads to Rab5 activation and endosome fusion in cellular assays; this interaction operates in Frizzled/Wingless GPCR signaling pathways for planar cell polarity. In vitro binding assay with purified proteins, fly extract co-IP, cellular endosome fusion assay, genetic epistasis in Drosophila Science signaling Medium 20736485
2011 Rab5a activity increases at the leading edge of migrating tumor cells; Rab5a (GTP-bound form) associates with focal adhesion proteins vinculin and paxillin, promotes focal adhesion disassembly and FAK dephosphorylation (Tyr397), and is required for cancer cell migration and invasion. Rab5 biosensor/pulldown assay, shRNA knockdown, dominant-negative (S34N) rescue experiments, co-IP with focal adhesion proteins, FAK phosphorylation, Matrigel invasion assay Journal of cell science Medium 23813952
2011 On macropinosomes, Rab5a is activated immediately after membrane recruitment; activation increases continuously and uniformly before decreasing, with deactivation preceding dissociation by 1–12 min; active Rab5a stabilizes macropinosomes and its dynamics are coordinated by organelle size, microtubules, and vacuolar pH. FRET microscopy of Rab5a cycle on macropinosomes, live-cell imaging, microtubule depolymerization, bafilomycin treatment Traffic Medium 21910808
2012 EMC6, an ER-localized transmembrane protein, interacts with both RAB5A and Beclin 1 and co-localizes with the omegasome marker DFCP1; EMC6 deficiency impairs autophagosome formation, identifying EMC6 as a regulator of RAB5A-associated class III PI3K complex activity during autophagy. Co-IP (EMC6/RAB5A/Beclin1), immunofluorescence co-localization with DFCP1, siRNA knockdown autophagy assay Autophagy Medium 23182941
2014 RAB5A promotes formation of invadosomes and tumor invasion by driving RAB4- and RABENOSYN-5-dependent endo/exocytic cycles of MT1-MMP and β3 integrin, which are required for spatially localized HGF/MET signaling and invasive chemotaxis. shRNA knockdown, dominant-negative and constitutively active RAB5A expression, invadosome assay (matrix degradation), integrin and MT1-MMP trafficking assay, in vivo ductal carcinoma model The Journal of cell biology Medium 25049275
2014 Vacuolin-1 activates RAB5A GTPase activity to block autophagosome–lysosome and endosome–lysosome fusion; expression of dominant-negative RAB5A or its knockdown inhibited vacuolin-1-induced autophagy block, while constitutively active RAB5A alone suppressed autophagosome–lysosome fusion. RAB5A GTPase activity assay, dominant-negative expression, siRNA knockdown, autophagosome/lysosome co-localization assay, lysosomal pH measurement Autophagy Medium 25483964
2014 Rab5a is required in mouse oocytes for proper spindle length and kinetochore–microtubule attachment during meiosis; Rab5a depletion reduces centromere protein F (CENPF) at kinetochores by impairing nuclear lamina disassembly, revealing a non-endocytic role in meiotic progression. siRNA knockdown in oocytes, immunofluorescence, spindle morphometry, CENPF localization, nuclear lamina disassembly assay FASEB journal Medium 24876181
2014 PKCε phosphorylates Rab5a on Thr-7 in T-cells stimulated through LFA-1 or CXCR4; this phosphorylation regulates Rab5a trafficking to the leading edge and is functionally necessary for Rac1 activation, actin rearrangement, and T-cell migration. Co-IP (Rab5a/PKCε), phosphorylation site mapping (Thr-7), dominant-negative and phospho-mutant expression, Rac1 activation assay, migration assay The Journal of biological chemistry Medium 24872409
2015 DRG2 associates with PI3P-containing Rab5 endosomes via co-localization and interaction with EEA1 and Rab5; DRG2 depletion impairs Rab5-RabGAP5 interaction and Rab5 deactivation without affecting Rab5 endosome recruitment of RabGAP5, blocking transferrin recycling. Co-IP (DRG2/EEA1/Rab5/RabGAP5), siRNA depletion, transferrin recycling assay, Rab5 GTPase activity on endosomes Molecular biology of the cell Medium 26582392
2015 Rab5-mediated VE-cadherin internalization mediates LPS-induced endothelial barrier dysfunction; LPS activates Rab5 and promotes VE-cadherin co-localization with Rab5 intracellularly; siRNA knockdown of Rab5a attenuates VE-cadherin internalization and protects barrier function in vitro and in vivo. siRNA knockdown, Rab5 activation assay, immunofluorescence co-localization, endothelial permeability assay in vitro and in vivo Cellular and molecular life sciences Medium 26112597
2017 Rab5-positive early endosomes sequester damaged mitochondria via ESCRT machinery in a Parkin-dependent manner; this endosomal pathway for mitochondrial clearance is initiated before autophagy, requires Beclin1 for Rab5 activation, and its abrogation causes accumulation of stressed mitochondria and increased cell death. Live-cell imaging, electron microscopy, ESCRT knockdown, Rab5 dominant-negative expression, Parkin and Beclin1 genetic manipulation, mitochondrial stress assays Nature communications High 28134239
2017 Site-specific monoubiquitination of Rab5 on K140 impedes interactions with downstream effectors, while monoubiquitination on K165 alters GDP release and GTP loading; structural models by solution scattering revealed site-specific conformational differences; K140R and K165R mutations rescue abnormal endosomal localization and EGF receptor degradation. Ubiquitin co-transfection, site-directed mutagenesis (K116R/K140R/K165R), solution X-ray scattering structural modeling, EGF receptor degradation assay, endosomal localization by immunofluorescence, GEF/GAP biochemical assays eLife High 28968219
2017 VPS34 negatively regulates RAB-5 via recruitment of the TBC-domain RabGAP TBC-2 to endosomes through a PI(3)P-dependent mechanism, forming a regulatory loop that ensures directionality of endosome maturation; Vps34 knockout increases Rab5 activity in mouse embryonic fibroblasts. C. elegans genetic epistasis, TBC-2/PH domain PI3P binding assay, Vps34 knockout MEFs (Rab5 activity assay), endosome size phenotype analysis Journal of cell science Medium 28455411
2018 Upon oxidative stress, Rab5 translocates from early endosomes to mitochondria in a reversible manner; this translocation depends on the Rab5-GEF Alsin (ALS2); Alsin-deficient iPSC-derived motor neurons are defective in relocating Rab5 to mitochondria and show increased susceptibility to oxidative stress. Live-cell imaging, subcellular fractionation, Alsin-deficient iPSC-derived motor neurons, oxidative stress assay, immunofluorescence eLife High 29469808
2019 Rab5-dependent ESCRT-mediated autophagosome closure requires a Rab5-controlled Atg17–Snf7 interaction that recruits ESCRT to open autophagosomes; depletion of ESCRT subunits Snf7 or Vps4 accumulates open autophagosomes. ESCRT subunit knockdown, autophagosome closure assay, co-IP (Atg17-Snf7), in vitro and in vivo complementation, Rab5 dominant-negative epistasis The Journal of cell biology Medium 31010855
2019 Rab5 is required for macropinosome sealing/scission downstream of ruffling; Rab5-containing vesicles fuse with circular ruffles via SNARE-dependent fusion; Rab5 mediates recruitment of inositol 5-phosphatases OCRL and Inpp5b via APPL1 to remove PtdIns(4,5)P2 needed for macropinosome closure. Dominant-negative Rab5, SNARE inhibition, OCRL/Inpp5b/APPL1 knockdown, PtdIns(4,5)P2 biosensor, macropinosome formation assay Journal of cell science Medium 33722976
2019 Rab5-APPL1 endosomes in hippocampal neurons undergo predominantly retrograde axonal transport; APPL1 endosomal levels correlate with faster retrograde movement; FRET showed APPL1-Akt1 interaction is endocytosis-dependent; APPL1 endosomes transport TrkB and mediate retrograde axonal transport of Akt1. Live-cell imaging in primary hippocampal neurons, FRET analysis, immunofluorescence of endogenous proteins, endocytosis inhibition Scientific reports Medium 30792402
2020 Rab5a directly interacts with IRS1 in a GTP-dependent manner; specific residues Arg207/Arg222 on IRS1 and Tyr82/Tyr89/Tyr90 on Rab5a mediate association. Rab5a promotes IRS1 activation by coordinating IRS1-IGFR association and membrane targeting; myogenic deletion of Rab5a reduces IGF-AKT-mTOR signaling and impairs muscle regeneration. Co-IP (Rab5a/IRS1, GTP-dependent), site-directed mutagenesis, conditional Rab5a knockout mice, IGF signaling assays (AKT/mTOR phosphorylation), myoblast differentiation assay Cell death and differentiation High 32051546
2020 A non-linear patterning system consisting of Rab5, RabGDI, and the GEF/effector complex Rabex5/Rabaptin5 is necessary and sufficient to pattern Rab5 into membrane domains on supported lipid bilayers; a 'handover' of Rab5 from Rabex5 to Rabaptin5 upon nucleotide exchange drives this patterning; PI(3)P enhances membrane recruitment and lipid acyl chain packing is critical for domain formation. Reconstitution on supported lipid bilayers, TIRF microscopy, purified components (Rab5, RabGDI, Rabex5, Rabaptin5), lipid composition variation eLife High 32510320
2021 Rab5a-GTP recruits endocytic VPS34 complex II to membranes and activates it by binding between the VPS34 C2 and VPS15 WD40 domains; cryo-ET of complex II on Rab5a-decorated vesicles shows that the VPS34 kinase domain is released from VPS15 inhibition over the lipid bilayer, poised for catalysis. Cryo-electron tomography, pulldown/binding assays, VPS34 lipid kinase activity assay on liposomes, Rab1a activation of complex I comparison Nature communications High 33692360
2021 AMPK phosphorylates TBC1D17 on Ser168, enhancing its autoinhibition and reducing its GAP activity toward Rab5, thereby allowing Rab5 activation to promote GLUT1/GLUT4 translocation and glucose uptake in muscle cells. Co-IP (TBC1D17/Rab5/AMPK), in vitro GAP assay, Ser168 phosphorylation mutagenesis, GLUT4 translocation assay, intramolecular interaction assay Cell death and differentiation Medium 34045668
2021 Complete depletion of all three Rab5 isoforms (Rab5A, Rab5B, Rab5C) via auxin-inducible degron causes loss of early and late endosomes but not lysosomes, dramatically reduces receptor-mediated and fluid-phase endocytosis, and leads to cell death within 48 h. Auxin-inducible conditional triple knockout, immunofluorescence, endocytosis assay (receptor-mediated and fluid-phase), organelle marker analysis Journal of cell science High 34817057
2022 TBC1D18 is a novel Rab5-GAP that associates with Mon1 and mediates endosome maturation; Rab5 hyperactivation (not Rab7 inactivation) is the primary cause of maturation defects in Mon1-KO cells; TBC1D18 expression in Mon1-KO cells rescues endosome maturation, while its depletion attenuates endosome formation and cargo degradation. Comprehensive screening of TBC domain-containing RabGAPs, TBC1D18 Co-IP with Mon1, Mon1-KO rescue experiments, endosome maturation assay, cargo degradation assay The Journal of cell biology Medium 36197338
2023 The pentameric FERRY complex is a Rab5 effector that binds mRNAs and ribosomes and recruits them to early endosomes; Fy-2 serves as binding hub for Rab5, other subunits, and mRNA; cryo-EM structure reveals a unique clamp-like architecture; FERRY displays preferential binding to mRNAs encoding mitochondrial proteins; deletion causes severe brain damage. Cryo-EM structure determination, pulldown (FERRY/Rab5/mRNA), functional mRNA localization assay in cells and neurons, mutagenesis of Rab5-binding interface, deletion of FERRY subunits Molecular cell High 37267905 37267906
2024 Rab5a mediates internalisation of NETs (neutrophil extracellular traps) by macrophages; NE (neutrophil elastase) within NETs activates Rab5a-NF-κB signaling to promote inflammatory cytokine secretion; Rab5a knockout mice exhibit reduced arthritis severity in a collagen-induced arthritis model. siRNA and Rab5a knockout mice, co-localization of NETs with early endosome markers, Rab5a-NF-κB pathway analysis, cytokine ELISA, arthritis severity scoring RMD open Medium 38485453
2006 Rab5 and Rab5a regulate insulin receptor-mediated endocytosis and signaling; Rab5:WT and Q79L enhance insulin-stimulated Erk1/2 and Akt activation while Rab5:S34N blocks both, without affecting JNK or p38, demonstrating isoform-specific Rab5 control of insulin receptor signaling. Overexpression and siRNA depletion of Rab5, fluid-phase and receptor-mediated endocytosis assays, kinase phosphorylation assays, DNA synthesis assay Archives of biochemistry and biophysics Medium 16554017
2010 CMTM3 interacts with Rab5 (by Co-IP), co-localizes with Rab5 on early endosomes, and markedly increases Rab5 GTPase activity; CMTM3-mediated acceleration of EGFR degradation and suppression of EGF-driven migration are abrogated by Rab5 siRNA. Co-IP, immunofluorescence co-localization, Rab5 GTPase activation assay, siRNA knockdown epistasis, EGFR degradation assay Cancer letters Medium 27867015
2020 BDNF-induced sustained Erk1/2 activation, nuclear CREB phosphorylation, and transcription of a BDNF-dependent gene program require Rab5 (and Rab11) activity; dominant-negative Rab5 blocks these nuclear signaling outcomes downstream of TrkB, establishing the Rab5-Rab11 endosomal pathway as required for signal integration from plasma membrane to nucleus in neurons. Dominant-negative Rab5 and Rab11 expression in rat hippocampal neurons, Erk1/2 and CREB phosphorylation assays, CRE-luciferase reporter, qPCR for target genes The Journal of neuroscience Medium 32928890
2020 Diaph1 (mDia1) directly interacts with both TβRII and Rab5a via its N-terminal domain; Diaph1 increases Rab5a GTPase activity; active Rab5a (Q79L) promotes endosomal localization of TβRII whereas inactive Rab5a (S34N) reduces it; Diaph1 or Rab5a targeting suppresses TGFβ-induced HSC myofibroblast activation and tumor growth. Co-IP (Diaph1/TβRII/Rab5a), Rab5a activity assay, Rab5a mutant expression, TβRII trafficking assay, SMAD3 phosphorylation, shRNA knockdown, in vivo tumor model FASEB journal Medium 32304339

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 rab5 controls early endosome fusion in vitro. Cell 981 1900457
2003 Modulation of Rab5 and Rab7 recruitment to phagosomes by phosphatidylinositol 3-kinase. Molecular and cellular biology 272 12640132
2000 The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Nature 245 11099046
2000 Epidermal growth factor and membrane trafficking. EGF receptor activation of endocytosis requires Rab5a. The Journal of cell biology 202 11062256
2003 Differential requirements of Rab5 and Rab7 for endocytosis of influenza and other enveloped viruses. Traffic (Copenhagen, Denmark) 186 12713661
2001 Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. The Journal of biological chemistry 169 11316809
2017 A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance. Nature communications 164 28134239
2004 Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. The Journal of biological chemistry 164 15033976
2002 Role of Rab5 in the recruitment of hVps34/p150 to the early endosome. Traffic (Copenhagen, Denmark) 160 12010460
2019 Rab5-dependent autophagosome closure by ESCRT. The Journal of cell biology 137 31010855
1994 The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis. Neuron 134 8043272
1999 Biochemical analysis of distinct Rab5- and Rab11-positive endosomes along the transferrin pathway. Journal of cell science 131 10574724
2005 Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons. Trends in cell biology 126 16330212
2014 A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination. The Journal of cell biology 114 25049275
2010 Regional selectivity of rab5 and rab7 protein upregulation in mild cognitive impairment and Alzheimer's disease. Journal of Alzheimer's disease : JAD 106 20847427
2014 Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A. Autophagy 100 25483964
2021 Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes. Nature communications 97 33692360
2017 Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochemical and biophysical research communications 94 28834690
1999 Dynamin and rab5 regulate GRK2-dependent internalization of dopamine D2 receptors. European journal of biochemistry 91 10406971
2003 Rab5 and Rab11 mediate transferrin and anti-variant surface glycoprotein antibody recycling in Trypanosoma brucei. The Biochemical journal 90 12744719
2013 Rab5 activation promotes focal adhesion disassembly, migration and invasiveness in tumor cells. Journal of cell science 80 23813952
2018 Rab5 and Alsin regulate stress-activated cytoprotective signaling on mitochondria. eLife 73 29469808
2011 Cannabinoid receptor 2 undergoes Rab5-mediated internalization and recycles via a Rab11-dependent pathway. Biochimica et biophysica acta 72 21640764
2020 The Emerging Role of Rab5 in Membrane Receptor Trafficking and Signaling Pathways. Biochemistry research international 71 32104603
2009 Rab5 mediates caspase-8-promoted cell motility and metastasis. Molecular biology of the cell 70 19923319
2015 MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast cancer by targeting the RAB5A. International journal of clinical and experimental pathology 69 25755726
1999 Increased expression of Rab5a correlates directly with accelerated maturation of Listeria monocytogenes phagosomes. The Journal of biological chemistry 69 10206948
1998 Protein kinase B/akt and rab5 mediate Ras activation of endocytosis. The Journal of biological chemistry 69 9677351
2000 Dynamics of rab5 activation in endocytosis and phagocytosis. Journal of leukocyte biology 68 11073100
1999 Rab5 induces Rac-independent lamellipodia formation and cell migration. Molecular biology of the cell 67 10512863
2004 Role of rab5 in EGF receptor-mediated signal transduction. European journal of cell biology 66 15511088
2017 Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells. Journal of virology 61 28724764
2007 Characterization of a Listeria monocytogenes protein interfering with Rab5a. Traffic (Copenhagen, Denmark) 61 18088303
1996 Characterization of Rab5:Q79L-stimulated endosome fusion. Archives of biochemistry and biophysics 60 8579373
2003 Rab5a and rab11a mediate agonist-induced trafficking of protease-activated receptor 2. American journal of physiology. Cell physiology 59 12540381
2001 Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1 receptor. The Journal of biological chemistry 59 11306580
2003 Rabip4' is an effector of rab5 and rab4 and regulates transport through early endosomes. Molecular biology of the cell 58 14617813
2012 A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy. Autophagy 57 23182941
2016 CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer. Cancer letters 56 27867015
1998 Interferon-gamma selectively induces Rab5a synthesis and processing in mononuclear cells. The Journal of biological chemistry 56 9852039
2007 Rab5 mediates an amyloid precursor protein signaling pathway that leads to apoptosis. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 17611268
2002 SARA, a FYVE domain protein, affects Rab5-mediated endocytosis. Journal of cell science 55 12432064
2019 Disruption of Endolysosomal RAB5/7 Efficiently Eliminates Colorectal Cancer Stem Cells. Cancer research 54 30765602
2007 Expression of Rab5a in hepatocellular carcinoma: Possible involvement in epidermal growth factor signaling. Hepatology research : the official journal of the Japan Society of Hepatology 52 17581187
2010 Rab5a overexpression promoting ovarian cancer cell proliferation may be associated with APPL1-related epidermal growth factor signaling pathway. Cancer science 51 20412119
1995 Biochemical and functional characterization of a recombinant GTPase, Rab5, and two of its mutants. The Journal of biological chemistry 51 7890612
2018 GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. Journal of the American Society of Nephrology : JASN 50 29959197
2023 The Rab5 effector FERRY links early endosomes with mRNA localization. Molecular cell 48 37267905
2020 GPA5 Encodes a Rab5a Effector Required for Post-Golgi Trafficking of Rice Storage Proteins. The Plant cell 48 31949008
2010 A direct and functional interaction between Go and Rab5 during G protein-coupled receptor signaling. Science signaling 48 20736485
2011 Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway. Journal of biomedical science 47 21849022
2004 Continual expression of Rab5(Q79L) causes a ligand-independent EGFR internalization and diminishes EGFR activity. Traffic (Copenhagen, Denmark) 47 15260830
2016 Hypoxia promotes Rab5 activation, leading to tumor cell migration, invasion and metastasis. Oncotarget 45 27121131
2014 Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration. The Journal of biological chemistry 45 24872409
2021 AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake. Cell death and differentiation 43 34045668
2017 The VPS34 PI3K negatively regulates RAB-5 during endosome maturation. Journal of cell science 43 28455411
2009 Endocytosis of adiponectin receptor 1 through a clathrin- and Rab5-dependent pathway. Cell research 42 18982021
2020 Rab5a activates IRS1 to coordinate IGF-AKT-mTOR signaling and myoblast differentiation during muscle regeneration. Cell death and differentiation 41 32051546
2011 Coordination of the Rab5 cycle on macropinosomes. Traffic (Copenhagen, Denmark) 41 21910808
2015 Rab5-mediated VE-cadherin internalization regulates the barrier function of the lung microvascular endothelium. Cellular and molecular life sciences : CMLS 38 26112597
2005 Inhibition of Rab5a exchange activity is a key step for Listeria monocytogenes survival. Traffic (Copenhagen, Denmark) 37 15702993
2023 RNA demethylase ALKBH5 promotes colorectal cancer progression by posttranscriptional activation of RAB5A in an m6A-YTHDF2-dependent manner. Clinical and translational medicine 36 37203239
1999 Differential expression of RAB5A in human lung adenocarcinoma cells with different metastasis potential. Clinical & experimental metastasis 36 10432006
2020 A non-linear system patterns Rab5 GTPase on the membrane. eLife 35 32510320
2020 P38α MAPK Signaling-A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease. International journal of molecular sciences 35 32751991
2019 Flotillins promote T cell receptor sorting through a fast Rab5-Rab11 endocytic recycling axis. Nature communications 35 31558725
2014 Rab5a is required for spindle length control and kinetochore-microtubule attachment during meiosis in oocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 35 24876181
2020 The Rab5-Rab11 Endosomal Pathway is Required for BDNF-Induced CREB Transcriptional Regulation in Hippocampal Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 32928890
2021 The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7. Cell reports 31 34731620
2017 Site-specific monoubiquitination downregulates Rab5 by disrupting effector binding and guanine nucleotide conversion. eLife 31 28968219
2014 Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole. Nature communications 31 24667230
2021 Rab5 regulates macropinocytosis by recruiting the inositol 5-phosphatases OCRL and Inpp5b that hydrolyse PtdIns(4,5)P2. Journal of cell science 30 33722976
2016 Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania. The Journal of biological chemistry 30 27226564
2016 Newcastle disease virus employs macropinocytosis and Rab5a-dependent intracellular trafficking to infect DF-1 cells. Oncotarget 30 27861142
2015 Developmentally regulated GTP-binding protein 2 coordinates Rab5 activity and transferrin recycling. Molecular biology of the cell 30 26582392
2006 Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis. Biochemical and biophysical research communications 29 16410077
2019 Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome. Scientific reports 28 30792402
2024 Internalisation of neutrophils extracellular traps by macrophages aggravate rheumatoid arthritis via Rab5a. RMD open 27 38485453
2018 Integration of two RAB5 groups during endosomal transport in plants. eLife 27 29749929
2014 Loss of Rab5 drives non-autonomous cell proliferation through TNF and Ras signaling in Drosophila. Developmental biology 27 25224221
2011 Rab5 in the regulation of cell motility and invasion. Current protein & peptide science 27 21190523
2017 Rab5a is overexpressed in oral cancer and promotes invasion through ERK/MMP signaling. Molecular medicine reports 26 28849149
2017 Subversion of RAB5-regulated autophagy by the intracellular pathogen Ehrlichia chaffeensis. Small GTPases 25 28650718
2006 Role of Rab5 in insulin receptor-mediated endocytosis and signaling. Archives of biochemistry and biophysics 25 16554017
2023 Structural basis of mRNA binding by the human FERRY Rab5 effector complex. Molecular cell 24 37267906
2020 Long Noncoding RNA TP53TG1 Contributes to Radioresistance of Glioma Cells Via miR-524-5p/RAB5A Axis. Cancer biotherapy & radiopharmaceuticals 24 32762546
2014 On the role of Rab5 in cell migration. Current molecular medicine 24 24467205
2022 TBC1D18 is a Rab5-GAP that coordinates endosome maturation together with Mon1. The Journal of cell biology 23 36197338
2021 RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer. Nature communications 23 34741021
2023 ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity. Molecular psychiatry 22 36604604
2014 Rab5 and Ndfip1 are involved in Pten ubiquitination and nuclear trafficking. Traffic (Copenhagen, Denmark) 22 24798731
2022 Hsa_circ_0001756 promotes ovarian cancer progression through regulating IGF2BP2-mediated RAB5A expression and the EGFR/MAPK signaling pathway. Cell cycle (Georgetown, Tex.) 21 35113003
2014 Expression pattern of the PRDX2, RAB1A, RAB1B, RAB5A and RAB25 genes in normal and cancer cervical tissues. International journal of oncology 21 25339198
2008 Agonist-dependent internalization and trafficking of the human prostacyclin receptor: a direct role for Rab5a GTPase. Biochimica et biophysica acta 21 18498773
2014 Rab5 activation as a tumor cell migration switch. Small GTPases 20 25763873
2019 TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway. Cancer cell international 19 31572059
2001 Dimerization of small GTPase Rab5. International journal of molecular medicine 19 11562778
2021 Establishment and analysis of conditional Rab1- and Rab5-knockout cells using the auxin-inducible degron system. Journal of cell science 18 34817057
2020 Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 32304339
2015 Overexpression of Rab5a promotes hepatocellular carcinoma cell proliferation and invasion via FAK signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 26443539

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