Affinage

RAB9A

Ras-related protein Rab-9A · UniProt P51151

Length
201 aa
Mass
22.8 kDa
Annotated
2026-04-28
75 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB9A is a late-endosomal Rab GTPase that orchestrates retrograde vesicular transport of mannose 6-phosphate receptors and other cargo from late endosomes to the trans-Golgi network, and additionally drives a non-canonical, Atg5/LC3-independent autophagy/mitophagy pathway. Prenylated Rab9A is delivered to late endosome membranes as a GDP-bound complex with GDI, where endosome-associated exchange factors trigger GTP loading; GTP-Rab9A then recruits effectors including TIP47 (which couples cargo selection to organelle identity), p40, GCC185, Nde1 (linking endosomes to dynein for retrograde motility), BLOC-3, and RUTBC1/2 (GAPs for Rab32/33B and Rab34/36, respectively), while GDI selectively extracts GDP-Rab9A to maintain its membrane cycling (PMID:8440258, PMID:11359012, PMID:34793709, PMID:8389620, PMID:21808068, PMID:22637480). ULK1-mediated phosphorylation of Rab9A at S179 enables an alternative mitophagy pathway in which a Ulk1/Rab9/Rip1/Drp1 complex recruits trans-Golgi membranes to damaged mitochondria, and loss of this phosphorylation exacerbates cardiac ischemic injury in vivo (PMID:30511961). GDP-bound Rab9A is subject to rapid VCP/p97-dependent proteasomal degradation through a conformation-dependent hydrophobic degron in switch I, and this turnover is required for proper CI-MPR trafficking (PMID:41628772).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1993 High

    Establishing that Rab9 is the specific Rab GTPase required for late-endosome-to-TGN MPR transport resolved which of the late-endosomal Rabs controls this recycling step and demonstrated that Rab specificity (not just Rab presence) determines transport pathway identity.

    Evidence Cell-free transport reconstitution with prenylated Rab9 vs. Rab7, subcellular fractionation, and purified GTPase kinetic assays

    PMID:8440258 PMID:8463223

    Open questions at the time
    • GEF identity unknown
    • GAP identity unknown
    • no structural information on Rab9
  2. 1993 High

    Demonstrating that cytosolic Rab9 exists as a prenylated complex with GDI that is extracted only in the GDP state established the membrane recycling mechanism for Rab9 and showed how nucleotide state governs membrane residency.

    Evidence Gel filtration, analytical ultracentrifugation, and GDI extraction assay with purified prenylated Rab9

    PMID:8389620

    Open questions at the time
    • Mechanism of GDI release at membranes unknown
    • Identity of membrane receptor for Rab9-GDI unknown
  3. 1994 High

    Showing that membrane delivery from GDI-Rab9 complexes is coupled to endosome-triggered nucleotide exchange, and that GDI is essential for cytosol-dependent transport, linked Rab9 activation to organelle-specific recruitment machinery.

    Evidence In vitro reconstitution of membrane recruitment with purified Rab9-GDI, nucleotide exchange assay, immunodepletion/add-back in cell-free transport

    PMID:8164745 PMID:8195183

    Open questions at the time
    • Molecular identity of the GEF unresolved
    • Stoichiometry of recruitment on native membranes unknown
  4. 1994 High

    Dominant-negative Rab9 S21N specifically blocked MPR recycling in living cells without affecting other endocytic or biosynthetic routes, validating the cell-free findings and establishing Rab9 as a pathway-specific regulator in vivo.

    Evidence Dominant-negative expression in cultured cells with pulse-chase and secretion assays

    PMID:7909812

    Open questions at the time
    • No loss-of-function genetic model yet
    • Downstream coat/tethering machinery unknown
  5. 1995 High

    Demonstrating that Rab9 and Rab7 are recruited to the same late endosome by biochemically distinct machinery explained how a single organelle can host multiple Rab domains controlling different trafficking steps.

    Evidence Competitive inhibition of Rab-GDI recruitment onto late endosome membranes in vitro

    PMID:7592724

    Open questions at the time
    • Molecular identity of Rab9-specific recruitment factor (GEF/receptor) still undefined
  6. 1997 High

    Identification of p40 as the first GTP-specific Rab9 effector that stimulates MPR transport provided the first downstream component of the Rab9 pathway.

    Evidence Yeast two-hybrid, recombinant protein reconstitution in cell-free transport assay, antibody inhibition

    PMID:9230071

    Open questions at the time
    • Precise function of p40 on late endosome membranes unknown
    • Relationship to other effectors uncharacterized
  7. 2001 High

    Showing that Rab9-GTP directly increases TIP47 affinity for MPR cytoplasmic domains revealed how a Rab GTPase couples cargo recognition to organelle identity, a paradigm for Rab-effector-cargo coupling.

    Evidence Direct binding assays, affinity measurements, and rescue with binding-deficient TIP47 mutants in living cells

    PMID:11359012 PMID:12032303

    Open questions at the time
    • Structure of the ternary Rab9–TIP47–MPR complex unavailable
    • Whether TIP47 functions as a coat component unclear
  8. 2002 High

    Live imaging of Rab9-positive transport intermediates revealed that Rab9 occupies distinct late endosomal microdomains from Rab7, enriched in CI-MPR, and is removed upon vesicle fusion with the TGN, establishing the spatiotemporal dynamics of the Rab9 transport cycle in living cells.

    Evidence GFP-Rab9 live-cell imaging, co-expression with fluorescent Rab7, video microscopy

    PMID:11827983

    Open questions at the time
    • Mechanism of Rab9 removal at TGN fusion undefined
    • Role of Rab9 in tethering/fusion not resolved
  9. 2003 High

    Linking PIKfyve to p40 phosphorylation and membrane retention connected lipid kinase signaling to Rab9 effector function on late endosomes.

    Evidence Yeast two-hybrid, co-IP, in vitro kinase assay, kinase-dead PIKfyve expression causing p40 membrane depletion

    PMID:14530284

    Open questions at the time
    • Phosphorylation site on p40 not mapped
    • In vivo significance for MPR transport not fully tested
  10. 2004 High

    RNAi depletion of Rab9 demonstrated its necessity for late endosome morphology, lysosomal enzyme sorting, and MPR localization in vivo, and revealed that Rab9 stability on endosomes depends on its effector TIP47.

    Evidence siRNA knockdown with quantitative EM morphometry, flow cytometry, pulse-chase in cultured cells

    PMID:15456905

    Open questions at the time
    • Genetic knockout model not yet available
    • Whether other Rabs compensate partially unknown
  11. 2006 High

    Two key regulatory insights emerged: TIP47 concentration determines Rab9 steady-state localization (effector-driven Rab domain identity), and cholesterol accumulation in NPC1 disease sequesters Rab9 on membranes by blocking GDI extraction, explaining MPR missorting in Niemann-Pick C.

    Evidence Rab chimera localization with TIP47 titration; cholesterol-dose-dependent GDI extraction of Rab9 from liposomes and NPC1 cell fractionation with Rab9 overexpression rescue

    PMID:16644737 PMID:16769818

    Open questions at the time
    • How cholesterol physically impedes GDI-Rab9 interaction not structurally resolved
    • Whether Rab9 overexpression is a viable NPC therapeutic strategy untested in vivo
  12. 2010 High

    Identification of BLOC-3 (HPS1-HPS4) as a GTP-specific Rab9A effector linked Rab9 to biogenesis of lysosome-related organelles and Hermansky-Pudlak syndrome biology, though subsequent separation-of-function analysis showed BLOC-3's Rab9-binding is dispensable for melanogenesis.

    Evidence Recombinant reconstitution with nucleotide-state-specific binding; later, HPS4 mutants lacking Rab9 binding fully rescued melanocyte pigmentation

    PMID:20048159 PMID:30837268

    Open questions at the time
    • Functional role of Rab9–BLOC-3 interaction remains undefined if not required for melanogenesis
    • Whether Rab9–BLOC-3 operates in other LRO-containing cell types unknown
  13. 2011 High

    RUTBC1 and RUTBC2 were identified as Rab9A-GTP-binding proteins that function not as Rab9 GAPs but as Rab9-recruited GAPs for Rab32/33B and Rab34/36 respectively, establishing Rab9A as a hub that coordinates inactivation of adjacent Rab pathways through effector-embedded GAP domains.

    Evidence GST pulldown, in vitro GAP assays with catalytic arginine mutants, cell-based membrane association assays

    PMID:21808068 PMID:22637480

    Open questions at the time
    • Physiological context for Rab9-RUTBC1/2-Rab32/34 cascade in cargo trafficking not defined
    • Structural basis of Rab9-RUTBC interaction unknown
  14. 2011 High

    Demonstrating that Rab9 and GCC185 are required for furin retrograde transport expanded the Rab9 cargo repertoire beyond MPRs to include additional TGN-resident proteins.

    Evidence Dominant-negative Rab9, siRNA knockdown of Rab9 and GCC185, chimeric receptor trafficking in cultured cells

    PMID:21693586

    Open questions at the time
    • Full repertoire of Rab9-dependent cargo undefined
    • Whether GCC185 acts as a tethering factor for Rab9 vesicles at the TGN not resolved
  15. 2019 High

    Rab9A was shown to function in an entirely distinct pathway — ULK1-mediated alternative (non-canonical) mitophagy — where phosphorylation at S179 by ULK1 enables a Rab9/Rip1/Drp1 complex to recruit trans-Golgi membranes to damaged mitochondria; this is essential for cardioprotection during ischemia.

    Evidence Rab9 S179A knockin mouse, co-immunoprecipitation of quaternary complex, in vivo ischemia model with mitophagy readouts

    PMID:30511961

    Open questions at the time
    • How S179 phosphorylation alters Rab9 effector specificity structurally unknown
    • Whether alternative mitophagy operates in tissues beyond heart untested genetically
    • Relationship between canonical Rab9 trafficking function and alternative autophagy unclear
  16. 2021 High

    The crystal structure of GTP-Rab9A bound to the Nde1 effector domain revealed how Rab9 tethers late endosomes to the dynein motor complex for retrograde transport, providing the first atomic-resolution view of Rab9 in complex with an effector.

    Evidence X-ray crystallography, mutagenesis of interface residues, co-immunoprecipitation with dynein/dynactin/Lis1

    PMID:34793709

    Open questions at the time
    • In vivo contribution of Nde1 vs. other effectors to Rab9-dependent transport not quantified
    • Whether Rab9-Nde1 interaction is regulated by phosphorylation unknown
  17. 2023 High

    Two studies extended Rab9 function into viral biology: NDP52 directs HBV envelope proteins to Rab9-dependent lysosomal degradation via a non-canonical antiviral pathway, while GDP-Rab9a (not GTP-Rab9a) supports retromer-mediated HPV endosomal exit, revealing that both nucleotide states of Rab9 have distinct functional roles in pathogen trafficking.

    Evidence Co-IP, siRNA knockdown of Rab9, viral replication/entry assays, nucleotide-state-specific mutant analysis

    PMID:37703297 PMID:38114531

    Open questions at the time
    • Mechanism by which GDP-Rab9a facilitates HPV-retromer association unclear
    • Whether Rab9-dependent antiviral lysosomal pathway operates against other viruses untested
  18. 2024 Medium

    TMEM9 was identified as an upstream activator of Rab9-dependent alternative autophagy, functioning by displacing Bcl-2 from Beclin1 at Rab9-positive autophagosomes, connecting lysosomal membrane sensing to non-canonical autophagy initiation.

    Evidence Co-immunoprecipitation, Bcl-2-binding domain mutagenesis, glycosylation mutants, autophagy flux assays

    PMID:39078420

    Open questions at the time
    • Single-lab finding awaiting independent confirmation
    • How TMEM9 signal is transduced to Rab9-positive membranes mechanistically incomplete
    • Whether TMEM9-dependent activation occurs in mitophagy vs. bulk alternative autophagy undefined
  19. 2026 High

    Discovery that GDP-Rab9a is rapidly degraded via a VCP/p97-dependent pathway recognizing a conformation-dependent hydrophobic degron in switch I revealed a quality control mechanism that maintains the appropriate GTP/GDP-Rab9a ratio required for CI-MPR trafficking.

    Evidence Protein stability assays, switch I mutagenesis, VCP/p97 identification, CI-MPR localization in degron mutants

    PMID:41628772

    Open questions at the time
    • Whether other Rab GTPases share CDH degron-mediated turnover unknown
    • Ubiquitin ligase(s) acting upstream of VCP/p97 on Rab9a not identified
    • How cells sense and adjust the GDP-Rab9a degradation rate unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The GEF responsible for endosomal Rab9 activation — the factor that triggers GDP-to-GTP exchange upon membrane delivery — has never been molecularly identified despite being functionally characterized in 1994, representing the longest-standing open question in Rab9 biology.
  • Rab9 GEF identity unknown
  • No GAP for Rab9 itself identified
  • Structural basis for how S179 phosphorylation switches Rab9 from trafficking to autophagy mode unresolved
  • Full in vivo phenotype of Rab9a genetic knockout not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3
Localization
GO:0005768 endosome 4 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-9609507 Protein localization 4 R-HSA-9612973 Autophagy 2 R-HSA-392499 Metabolism of proteins 1
Partners
GCC2GDI1HPS4NDE1PLIN3RABGEF1RUTBC1RUTBC2
Complex memberships
Rab9-GDI cytosolic complexUlk1/Rab9/Rip1/Drp1 alternative mitophagy complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Rab9 localizes primarily to the surface of late endosomes and, when prenylated in vitro, stimulates transport of mannose 6-phosphate receptors (MPRs) from late endosomes to the trans-Golgi network (TGN) in a cell-free reconstitution system; C-terminally truncated Rab9 was inactive, and Rab7 (also on late endosomes) was inactive in this assay despite efficient prenylation and GTP binding. In vitro prenylation, cell-free transport reconstitution assay, subcellular fractionation The EMBO journal High 8440258
1993 Rab9 GTPase activity: purified recombinant Rab9 hydrolyzes GTP (kcat ~0.0052 min⁻¹ at 37°C) and has nucleotide association/dissociation kinetics distinct from the closely related Rab7, providing the first biochemical characterization of this enzyme. In vitro GTPase assay, nucleotide binding kinetics with purified recombinant protein The Journal of biological chemistry High 8463223
1993 Cytosolic Rab9 exists as an ~80 kDa complex with GDI (GDP dissociation inhibitor); complex formation requires Rab9 carboxy-terminal geranylgeranylation, and purified Rab3A-GDI can solubilize Rab9-GDP but not Rab9-GTP from membranes, supporting a model in which GDI recycles Rab9 from target membranes after each transport cycle. In vitro prenylation, gel filtration/sedimentation, GDI extraction assay with purified components Molecular biology of the cell High 8389620
1994 Dominant-negative Rab9 S21N expressed in living cells specifically blocks MPR recycling from late endosomes to the TGN, leading to decreased lysosomal enzyme sorting efficiency; biosynthetic transport, fluid-phase endocytosis, and receptor-mediated endocytosis were unaffected. Dominant-negative mutant expression in living cells, pulse-chase and secretion assays The Journal of cell biology High 7909812
1994 Selective targeting of prenylated Rab9 onto late endosome membranes is reconstituted in vitro from GDI-Rab9 complexes and is accompanied by endosome-triggered GDP-to-GTP nucleotide exchange, demonstrating that membrane delivery and activation are coupled. In vitro membrane recruitment reconstitution, nucleotide exchange assay with purified prenylated Rab9-GDI complexes Nature High 8164745
1994 Rab9-GDI complexes represent a functional cytosolic pool that can be used for late-endosome-to-TGN transport; immunodepletion of GDI abolishes cytosol transport activity restored by re-addition of pure Rab9-GDI; GDI increases selectivity of Rab9 membrane targeting compared to albumin-delivered Rab9. Immunodepletion of cytosol, reconstitution with purified Rab9-GDI, cell-free transport assay The Journal of biological chemistry High 8195183
1995 Rab9 and Rab7, both late endosomal, are recruited onto late endosome membranes by biochemically distinguishable machinery: Rab9-GDI complexes competitively inhibit Rab9 recruitment with ~9 nM Ki but inhibit Rab7 recruitment much less effectively (~112 nM Ki), and vice versa, demonstrating that a single organelle bears multiple distinct Rab recruitment machines. In vitro Rab recruitment competition assay with purified prenylated Rab-GDI complexes The Journal of biological chemistry High 7592724
1997 p40, a novel 40-kDa Rab9 effector identified by yeast two-hybrid, binds Rab9-GTP with ~4-fold preference over Rab9-GDP, co-fractionates with late endosomes and Rab9, and potently stimulates MPR transport from endosomes to TGN in a cell-free assay; anti-p40 antibodies inhibit transport, and p40 shows synergy with Rab9. Yeast two-hybrid, subcellular fractionation, in vitro transport assay with purified recombinant p40, antibody inhibition The Journal of cell biology High 9230071
2001 TIP47 (tail-interacting protein of 47 kDa) binds directly to GTP-bound (active) Rab9, and Rab9 increases the affinity of TIP47 for MPR cytoplasmic domains; a functional Rab9-binding site in TIP47 is required for TIP47 stimulation of MPR transport in vivo, demonstrating that Rab9 couples cargo selection to organelle identity. Direct binding assay (GST pulldown), affinity measurements, dominant-negative and binding-mutant rescue in living cells Science High 11359012
2002 GFP-Rab9 localizes to late endosomes and occupies distinct membrane domains from Rab7 on the same organelle; cation-independent MPRs are enriched in Rab9 domains; Rab9-positive transport vesicles undergo bidirectional microtubule-dependent motility and fuse with the TGN, and Rab9 is rapidly removed coincident with or just after membrane fusion. GFP live-cell imaging, video microscopy, co-expression with fluorescent Rab7, fixed-cell colocalization The Journal of cell biology High 11827983
2002 TIP47 residues 161–169 are essential (but not sufficient) for Rab9 binding; mutations in this region decrease Rab9 binding without altering overall protein folding or MPR cytoplasmic domain binding, identifying distinct binding surfaces for Rab9 and cargo in TIP47. Site-directed mutagenesis, GST pulldown, circular dichroism spectroscopy, partial proteolysis Proceedings of the National Academy of Sciences High 12032303
2003 PIKfyve (a lipid/protein kinase) interacts with the Rab9 effector p40 via its chaperonin domain and p40 kelch repeats; kinase-dead PIKfyve depletes p40 from membranes, and PIKfyve phosphorylates p40 on serine in vitro, suggesting PIKfyve-mediated phosphorylation anchors p40 to late endosome membranes to support endosome-to-TGN transport. Yeast two-hybrid, GST pulldown, co-immunoprecipitation in HEK293 cells, differential centrifugation, in vitro kinase assay The Journal of biological chemistry High 14530284
2004 RNAi depletion of Rab9 decreases late endosome size, reduces multilamellar and dense-tubule-containing late endosomes/lysosomes, increases surface MPRs, causes MPR missorting to lysosomes, and clusters remaining late endosomes near the nucleus; additionally, Rab9 stability on late endosomes requires its interaction with the effector TIP47. siRNA knockdown, quantitative morphological analysis by EM, flow cytometry for surface MPRs, pulse-chase Molecular biology of the cell High 15456905
2006 TIP47 concentration controls Rab9 localization: Rab5/9 and Rab1/9 chimeras that can bind both parental Rab effectors shift localization toward Rab9 compartments when TIP47 levels are elevated, demonstrating that effector concentration is a determinant of Rab steady-state localization. Chimeric Rab construction, quantitative effector binding assay, fluorescence microscopy with modulation of TIP47 levels The Journal of cell biology High 16769818
2006 Cholesterol accumulation in NPC1-deficient cells sequesters Rab9 in an inactive state on endosome membranes by reducing GDI-mediated extraction (shown by cholesterol-dose-dependent decrease in GDI extractability of prenylated Rab9 from liposomes); sequestered Rab9 leads to MPR missorting, reversed by Rab9 overexpression. NPC1 cell fractionation, GDI extraction assay, liposome assay with increasing cholesterol, GFP-Rab9 rescue The Journal of biological chemistry High 16644737
2010 BLOC-3 (HPS1-HPS4 heterodimer) interacts specifically and strongly with GTP-bound Rab9 through HPS4 and the switch I/II regions of Rab9, identifying BLOC-3 as a Rab9A effector involved in biogenesis of lysosome-related organelles. Recombinant protein production, analytical ultracentrifugation, GST pulldown/interaction screen with Rab9 nucleotide-state specificity The Journal of biological chemistry High 20048159
2011 RUTBC1 (a TBC-domain protein) binds Rab9A-GTP in vitro and in cells but is not a GAP for Rab9A; instead it acts as a GAP for Rab32 and Rab33B (requiring catalytic Arg-803, consistent with dual-finger mechanism), linking Rab9A function to regulation of adjacent Rab32 pathway. GST pulldown, co-immunoprecipitation, in vitro GAP assay with Rab protein substrates, mutagenesis (R803A), effector binding assay in cells The Journal of biological chemistry High 21808068
2011 Rab9 and its effector GCC185 (a TGN golgin) are required for retrograde transport of furin from late endosomes to the TGN; furin transits early and late endosomes en route to the TGN, and its diversion to the early-endosome retromer pathway requires both the transmembrane domain and cytoplasmic tail of TGN38, implicating transmembrane domain length in endosomal sorting. Internalization assays, dominant-negative Rab9, siRNA knockdown of Rab9/GCC185, chimeric receptor trafficking analysis Journal of cell science High 21693586
2012 RUTBC2 (a TBC-domain protein) binds Rab9A-GTP specifically in vitro and in cells but is not a GAP for Rab9A; it acts as a GAP for Rab34 and Rab36 (requiring catalytic R829), and wild-type RUTBC2 but not R829A decreases membrane-associated Rab36 in cells, linking Rab9A to Rab36 regulation in the endosomal system. GST pulldown, co-immunoprecipitation, in vitro GAP assay with multiple Rab substrates, mutagenesis, co-localization The Journal of biological chemistry High 22637480
2019 During myocardial ischemia, mitophagy is mediated by Rab9-associated autophagosomes (alternative autophagy independent of Atg7/LC3); this involves a complex of Ulk1, Rab9, Rip1, and Drp1; Ulk1 phosphorylates Rab9 at S179 and Rip1 phosphorylates Drp1 at S616, recruiting trans-Golgi membranes to damaged mitochondria. Rab9 S179A knockin abolishes alternative mitophagy and exacerbates ischemic injury without affecting conventional autophagy. Knockin mouse (Rab9 S179A), co-immunoprecipitation of Ulk1/Rab9/Rip1/Drp1 complex, phosphorylation assays, in vivo ischemia model with mitophagy readouts The Journal of clinical investigation High 30511961
2019 HPS4 (BLOC-3 subunit) Rab32/38-GEF activity is essential for melanogenesis, but its Rab9-binding activity is dispensable; site-directed HPS4 mutants specifically lacking Rab9 binding fully rescued hypopigmentation in HPS4-deficient melan-le cells, showing Rab9 regulates melanogenesis independently of BLOC-3. Site-directed mutagenesis of HPS4, rescue of HPS4-deficient melanocyte cell line, melanin content and tyrosinase trafficking assays The Journal of biological chemistry High 30837268
2021 Nde1/Ndel1 is a Rab9A effector that tethers Rab9-positive late endosomes to the cytoplasmic dynein motor complex for retrograde transport; crystal structure of Rab9A-GTP in complex with the Rab9-binding region of Nde1 was determined, and key interface residues were validated biochemically; Rab9A mutants unable to bind Nde1 also failed to associate with dynein, Lis1, and dynactin. Crystal structure determination, biochemical pulldown, co-immunoprecipitation, mutagenesis of interface residues, cell biology assays Structure High 34793709
2009 Rab9 interacts with the intermediate filament protein vimentin; in NPC1 cells, lipid accumulation inhibits PKC, causing vimentin hypophosphorylation, intermediate filament aggregation, and entrapment of Rab9, which leads to late endosome transport defects and impaired lipid egress. Co-immunoprecipitation/pulldown for Rab9-vimentin interaction, PKC activity assay, phosphorylation analysis, lipid transport assay in NPC1 cells Biology of the cell Medium 18681838
2010 Rab9 co-localizes in vesicular structures with TRPC6 and co-immunoprecipitates with TRPC6; dominant-negative Rab9 S21N increases TRPC6 at the plasma membrane and enhances TRPC6-mediated Ca²⁺ entry, indicating Rab9-dependent late endosomal trafficking regulates TRPC6 surface density. Co-localization by confocal microscopy, co-immunoprecipitation, dominant-negative expression, Ca²⁺ entry measurements Biochimica et biophysica acta Medium 20346379
2016 Live imaging of constitutively active Rab9Q66L shows it localizes predominantly to late endosomes, disperses TGN46 and CI-MPR from the Golgi, and that CI-MPR and Rab9 enter the endosomal pathway together at the Rab5-to-Rab7 transition stage; CI-MPR vesicles attach and detach from Rab9-positive endosomal domains within seconds. Confocal live-cell imaging, constitutively active mutant (Rab9Q66L), CI-MPR retrograde transport assays Traffic Medium 26663757
2017 PKC activation promotes α1B-adrenoceptor transfer to late endosomes through Rab9 interaction; FRET imaging shows transient receptor-Rab5 interaction followed by sustained receptor-Rab9 interaction; dominant-negative Rab9-GDP abolishes receptor traffic and alters desensitization, implicating Rab9 in GPCR heterologous desensitization. FRET imaging, confocal microscopy, dominant-negative Rab9, PKC inhibition, Ca²⁺ quantitation Molecular pharmacology Medium 28082304
2023 NDP52 (CALCOCO2) forms a complex with Rab9 and HBV envelope proteins and links HBV to Rab9-dependent lysosomal degradation, inhibiting viral replication; this process is independent of galectin-8 and ATG5 (unlike antibacterial NDP52 autophagy), identifying a non-canonical antiviral lysosomal degradation pathway requiring Rab9. Co-immunoprecipitation, siRNA knockdown of Rab9, viral replication assays, lysosome targeting assays in hepatocytes Nature communications High 38114531
2023 GDP-bound (not GTP-bound) Rab9a supports retromer-mediated endosomal exit of HPV during virus entry; GTP-Rab9a inhibits HPV-retromer association and impairs endosome-to-Golgi transport; Rab9a acts upstream of Rab7 in this process and can regulate HPV-retromer interaction independently of Rab7. siRNA knockdown, dominant-negative and constitutively active Rab9a mutants, proximity assays, retromer co-immunoprecipitation, viral entry assays PLoS pathogens High 37703297
2024 TMEM9 (a lysosomal transmembrane protein) activates Rab9-dependent alternative autophagy by binding Beclin1 via its cytosolic Bcl-2-binding domain, displacing Bcl-2 and activating the Beclin1 complex at Rab9-positive autophagosomes; TMEM9 glycosylation required for lysosomal localization is essential for this interaction. Co-immunoprecipitation, mutagenesis of Bcl-2-binding domain, co-localization imaging, glycosylation mutants, autophagy flux assays Cellular and molecular life sciences Medium 39078420
2026 GDP-bound Rab9a contains a conformation-dependent hydrophobic (CDH) degron in its switch I region that is recognized by the protein quality control (PQC) machinery; GDP-Rab9a has an extremely short half-life relative to Rab7; VCP/p97 was identified as a CDH degron-dependent PQC factor; forced accumulation of CDH-degron-mutated Rab9a causes defective CI-MPR localization, demonstrating that rapid turnover of GDP-Rab9a is required for proper vesicular trafficking. Protein stability assays, amino acid sequence/structural comparison, mutagenesis of switch I hydrophobic residues, CI-MPR localization assays, VCP/p97 identification The Journal of biological chemistry High 41628772

Source papers

Stage 0 corpus · 75 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Rab9 functions in transport between late endosomes and the trans Golgi network. The EMBO journal 482 8440258
1994 Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network. The Journal of cell biology 265 7909812
2002 Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells. The Journal of cell biology 243 11827983
2019 An alternative mitophagy pathway mediated by Rab9 protects the heart against ischemia. The Journal of clinical investigation 224 30511961
2001 Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science (New York, N.Y.) 201 11359012
1994 Membrane targeting of the small GTPase Rab9 is accompanied by nucleotide exchange. Nature 172 8164745
1993 Rab GDI: a solubilizing and recycling factor for rab9 protein. Molecular biology of the cell 145 8389620
2004 Rab9 GTPase regulates late endosome size and requires effector interaction for its stability. Molecular biology of the cell 136 15456905
2005 Rab9 GTPase is required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. Journal of virology 128 16140752
1997 A novel Rab9 effector required for endosome-to-TGN transport. The Journal of cell biology 119 9230071
2006 Cholesterol accumulation sequesters Rab9 and disrupts late endosome function in NPC1-deficient cells. The Journal of biological chemistry 101 16644737
2006 TIP47 is a key effector for Rab9 localization. The Journal of cell biology 82 16769818
2002 Telomerase immortalization upregulates Rab9 expression and restores LDL cholesterol egress from Niemann-Pick C1 late endosomes. Journal of lipid research 81 12576506
2013 Rab9 and retromer regulate retrograde trafficking of luminal protein required for epithelial tube length control. Nature communications 77 23322046
2012 The small GTPases Rab9A and Rab23 function at distinct steps in autophagy during Group A Streptococcus infection. Cellular microbiology 75 22452336
2010 Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9. The Journal of biological chemistry 72 20048159
2001 Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9- and Rab11-GTPases. Molecular biology of the cell 71 11452006
2005 Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 69 15972801
1994 Rab-GDI presents functional Rab9 to the intracellular transport machinery and contributes selectivity to Rab9 membrane recruitment. The Journal of biological chemistry 69 8195183
1995 Rab7 and Rab9 are recruited onto late endosomes by biochemically distinguishable processes. The Journal of biological chemistry 63 7592724
2011 Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin. Journal of cell science 57 21693586
2003 Active PIKfyve associates with and promotes the membrane attachment of the late endosome-to-trans-Golgi network transport factor Rab9 effector p40. The Journal of biological chemistry 56 14530284
2011 RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32 and Rab33B proteins. The Journal of biological chemistry 52 21808068
2009 Endosomal lipid accumulation in NPC1 leads to inhibition of PKC, hypophosphorylation of vimentin and Rab9 entrapment. Biology of the cell 48 18681838
2013 TIP47 is associated with the hepatitis C virus and its interaction with Rab9 is required for release of viral particles. European journal of cell biology 44 24480419
2021 Estrogen Plays a Crucial Role in Rab9-Dependent Mitochondrial Autophagy, Delaying Arterial Senescence. Journal of the American Heart Association 39 33719502
1993 Biochemical analysis of rab9, a ras-like GTPase involved in protein transport from late endosomes to the trans Golgi network. The Journal of biological chemistry 39 8463223
2019 Long noncoding RNA ZFAS1 promotes tumorigenesis through regulation of miR-150-5p/RAB9A in melanoma. Melanoma research 36 30889053
2016 The multiple roles of Rab9 in the endolysosomal system. Communicative & integrative biology 36 27574541
2008 Development of a Rab9 transgenic mouse and its ability to increase the lifespan of a murine model of Niemann-Pick type C disease. The American journal of pathology 35 19056848
2011 Cellular vacuoles induced by Mycoplasma pneumoniae CARDS toxin originate from Rab9-associated compartments. PloS one 33 21829543
2016 Spatiotemporal Resolution of Rab9 and CI-MPR Dynamics in the Endocytic Pathway. Traffic (Copenhagen, Denmark) 32 26663757
2018 Rab9-dependent autophagy is required for the IGF-IIR triggering mitophagy to eliminate damaged mitochondria. Journal of cellular physiology 30 29574782
2002 Identification of residues in TIP47 essential for Rab9 binding. Proceedings of the National Academy of Sciences of the United States of America 30 12032303
2012 RUTBC2 protein, a Rab9A effector and GTPase-activating protein for Rab36. The Journal of biological chemistry 29 22637480
2019 The BLOC-3 subunit HPS4 is required for activation of Rab32/38 GTPases in melanogenesis, but its Rab9 activity is dispensable for melanogenesis. The Journal of biological chemistry 27 30837268
2010 Involvement of Rab9 and Rab11 in the intracellular trafficking of TRPC6. Biochimica et biophysica acta 27 20346379
2009 Phylogeny and evolution of Rab7 and Rab9 proteins. BMC evolutionary biology 27 19442299
2009 Human copper transporter 1 lacking O-linked glycosylation is proteolytically cleaved in a Rab9-positive endosomal compartment. The Journal of biological chemistry 26 19684018
2002 Selective regulation of the Rab9-independent transport of ricin to the Golgi apparatus by calcium. Journal of cell science 24 12154075
2021 Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia. Biochemical and biophysical research communications 22 33862456
2019 Ulk1/Rab9-mediated alternative mitophagy confers cardioprotection during energy stress. The Journal of clinical investigation 22 30667375
1997 Cloning and mapping of human Rab7 and Rab9 cDNA sequences and identification of a Rab9 pseudogene. Genomics 21 9126495
2024 IL-4 activates ULK1/Atg9a/Rab9 in asthma, NLRP3 inflammasomes, and Golgi fragmentation by increasing autophagy flux and mitochondrial oxidative stress. Redox biology 19 38373380
2019 Accumulation of sphingomyelin in Niemann-Pick disease type C cells disrupts Rab9-dependent vesicular trafficking of cholesterol. Journal of cellular physiology 19 31489965
2024 Selective induction of Rab9-dependent alternative mitophagy using a synthetic derivative of isoquinoline alleviates mitochondrial dysfunction and cognitive deficits in Alzheimer's disease models. Theranostics 16 38164158
2020 RAB9A Plays an Oncogenic Role in Human Liver Cancer Cells. BioMed research international 15 32420351
2021 Rab9 Mediates Pancreatic Autophagy Switch From Canonical to Noncanonical, Aggravating Experimental Pancreatitis. Cellular and molecular gastroenterology and hepatology 14 34610499
2017 Protein Kinase C Activation Promotes α1B-Adrenoceptor Internalization and Late Endosome Trafficking through Rab9 Interaction. Role in Heterologous Desensitization. Molecular pharmacology 14 28082304
2023 NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway. Nature communications 13 38114531
2019 The overexpression of Rab9 promotes tumor progression regulated by XBP1 in breast cancer. OncoTargets and therapy 13 30881034
2021 Nde1 is a Rab9 effector for loading late endosomes to cytoplasmic dynein motor complex. Structure (London, England : 1993) 12 34793709
2021 Circular RNA circSIPA1L1 Contributes to Osteosarcoma Progression Through the miR-411-5p/RAB9A Signaling Pathway. Frontiers in cell and developmental biology 11 33968929
2024 TMEM9 activates Rab9-dependent alternative autophagy through interaction with Beclin1. Cellular and molecular life sciences : CMLS 10 39078420
2020 Rab9 defense against white spot syndrome virus by participation in autophagy in Marsupenaeus japonicas. Fish & shellfish immunology 9 32526284
2020 Knockdown of Rab9 Suppresses the Progression of Gastric Cancer Through Regulation of Akt Signaling Pathway. Technology in cancer research & treatment 8 32301398
2000 cDNA cloning of a new member of the Ras superfamily, RAB9-like, on the human chromosome Xq22.1-q22.3 region. Journal of human genetics 8 11043518
2020 VARP and Rab9 Are Dispensable for the Rab32/BLOC-3 Dependent Salmonella Killing. Frontiers in cellular and infection microbiology 7 33392103
2018 Modulation of cis- and trans- Golgi and the Rab9A-GTPase during infection by Besnoitia besnoiti, Toxoplasma gondii and Neospora caninum. Experimental parasitology 7 29499180
2005 Purification and analysis of TIP47 function in Rab9-dependent mannose 6-phosphate receptor trafficking. Methods in enzymology 7 16473602
2023 Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. PLoS pathogens 6 37703297
2021 Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis. Open life sciences 5 34056112
2005 Analysis of potential binding of the recombinant Rab9 effector p40 to phosphoinositide-enriched synthetic liposomes. Methods in enzymology 5 16473631
2023 Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma. The journal of venomous animals and toxins including tropical diseases 4 37020694
2025 The Role of the Beclin1 Complex in Rab9-Dependent Alternative Autophagy. International journal of molecular sciences 3 41009712
2024 The host Rab9a/Rab32 axis is actively recruited to the Trypanosoma cruzi parasitophorous vacuole and benefits the infection cycle. Molecular microbiology 3 38193389
2023 Circ_0081054 facilitates melanoma development via sponging miR-637 and regulating RAB9A. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 3 37231931
2024 Age-associated accumulation of RAB9 disrupts oocyte meiosis. Aging cell 2 39676221
2004 Purification, crystallization and preliminary X-ray analysis of the GTP-binding protein Rab9 implicated in endosome-to-TGN vesicle trafficking. Acta crystallographica. Section D, Biological crystallography 2 14993700
2026 A conformation-dependent hydrophobic degron determines Rab9a-mediated vesicular trafficking. The Journal of biological chemistry 0 41628772
2026 Dehydroandrographolide succinate alleviates ulcerative colitis via regulating RAB9A/NF-κB axis-mediated macrophage polarization and remodeling the gut microbiota. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41930813
2025 Disruption of Rab9-dependent mitophagy contributes to menopause-induced sarcopenia. Experimental gerontology 0 41274424
2024 CALCOCO2/NDP52 associates with RAB9 to initiate an antiviral response to hepatitis B virus infection through a lysosomal degradation pathway. Autophagy 0 38752371
2024 Knockdown of Rab9 Recovers Defective Morphological Differentiation Induced by Chemical ER Stress Inducer or PMD-Associated PLP1 Mutant Protein in FBD-102b Cells. Pathophysiology : the official journal of the International Society for Pathophysiology 0 39311306
2023 Noncanonical Rab9a action supports endosomal exit of human papillomavirus during virus entry. bioRxiv : the preprint server for biology 0 37205481