Affinage

RAB6B

Ras-related protein Rab-6B · UniProt Q9NRW1

Length
208 aa
Mass
23.5 kDa
Annotated
2026-04-28
33 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB6B is a brain-enriched small GTPase of the Rab6 subfamily that cycles between GDP- and GTP-bound states to coordinate vesicular trafficking at the Golgi apparatus, functioning in both retrograde and anterograde transport pathways. In its GTP-bound form, RAB6B recruits effectors including Bicaudal-D1 (BICD1), which couples RAB6B-positive vesicles to the dynein/dynactin motor complex for minus-end-directed transport, and ELKS1, whose liquid-liquid phase separation captures RAB6B-coated vesicles at exocytic release sites; RAB6B also binds the dynein light chain DYNLRB1 preferentially in its GDP-bound state (PMID:17707369, PMID:37172719, PMID:18044744). Combined loss of Rab6a and Rab6b in radial glia abolishes polarized Golgi-to-apical delivery of Crumbs3, causing progenitor delamination, while in neurons it prevents axonal transport of synaptic vesicle precursors, resulting in severe neocortical and cerebellar dysplasia (PMID:35979738, PMID:38830762). RAB6B also promotes post-translational secretory trafficking of TNF in macrophages, and its membrane targeting depends on prenylation, which when pharmacologically blocked impairs integrin localization and downstream signaling (PMID:34555867, PMID:37277330).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2000 High

    Identification of RAB6B as a distinct Rab6 subfamily member with Golgi/ERGIC localization and interaction with known Rab6A effectors established that a second Rab6 isoform operates in retrograde Golgi trafficking.

    Evidence cDNA cloning, immunofluorescence, GTP-binding assays, and constitutively active mutant co-localization in mammalian cells

    PMID:10893188

    Open questions at the time
    • Endogenous expression pattern across tissues not fully resolved
    • Functional redundancy with Rab6A not tested
    • No loss-of-function data
  2. 2006 High

    High-resolution crystal structures of RAB6B in both nucleotide states revealed that conformational switching in switch I/II and the Rab6-specific RabSF3 region may underlie effector selectivity distinct from other Rab GTPases.

    Evidence X-ray crystallography at 2.3 Å (GDP) and 1.8 Å (GTPγS) resolution

    PMID:16790928

    Open questions at the time
    • No effector-bound structure to confirm RabSF3 role in selectivity
    • No mutagenesis of RabSF3 residues to test functional relevance
  3. 2007 High

    Demonstration that GTP-bound RAB6B recruits Bicaudal-D1 (BICD1) and co-localizes with dynein in neurites established the molecular link between RAB6B and the dynein/dynactin motor complex for bidirectional vesicle transport in neurons.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, pull-down, and live-cell imaging in SK-N-SH neuronal cells

    PMID:17707369

    Open questions at the time
    • Directionality of RAB6B-dependent cargo movement not resolved
    • No loss-of-function of BICD1 to test requirement for RAB6B transport
  4. 2008 High

    Discovery that RAB6B binds the dynein light chain DYNLRB1 preferentially in its GDP-bound state—unlike Rab6A—revealed nucleotide-state-specific effector engagement within the Rab6 subfamily, suggesting distinct regulatory modes.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and pull-down with nucleotide-loaded forms

    PMID:18044744

    Open questions at the time
    • Functional consequence of GDP-preferential binding not established
    • Whether DYNLRB1 acts as a GDI-like chaperone or transport regulator for RAB6B unknown
  5. 2021 Medium

    Knockdown of Rab6b in macrophages reduced TNF secretion without affecting mRNA or total protein levels, establishing a non-neuronal function for RAB6B in post-translational secretory trafficking of cytokines.

    Evidence siRNA knockdown, ELISA, qRT-PCR, and Western blot in BCG-infected primary mouse macrophages

    PMID:34555867

    Open questions at the time
    • Specific vesicle intermediate carrying TNF not identified
    • Rescue with wild-type or mutant RAB6B not shown
    • Single lab finding
  6. 2022 High

    Double knockout of Rab6a and Rab6b in radial glia proved that RAB6-mediated dynein-dependent Golgi-to-apical transport of Crumbs3 is essential for maintaining apical progenitor identity, resolving the in vivo cargo and pathway for polarized sorting.

    Evidence Double KO mice, in utero electroporation, live imaging of post-Golgi vesicles, genetic epistasis with LIS1 KO

    PMID:35979738

    Open questions at the time
    • Individual contributions of Rab6a versus Rab6b not separable in DKO
    • Whether RAB6B alone is sufficient for CRB3 transport not tested
  7. 2023 High

    The co-crystal structure of RAB6B with ELKS1 and reconstitution of ELKS1 liquid-liquid phase separation showed how ELKS1 condenses RAB6B-coated vesicles at exocytic sites, providing a structural and biophysical mechanism for RAB6B-directed vesicle exocytosis.

    Evidence X-ray crystallography of RAB6B–ELKS1 complex, in vitro LLPS reconstitution, liposome binding, and live-cell vesicle exocytosis imaging

    PMID:37172719

    Open questions at the time
    • In vivo validation of LLPS-dependent vesicle capture not performed
    • Whether ELKS1 LLPS is required for all RAB6B-dependent exocytosis or only at specific release sites unclear
  8. 2023 Medium

    Statin-mediated blockade of RAB6B prenylation impaired its membrane association and downstream integrin-FAK signaling in BRAF-inhibitor-resistant melanoma, linking RAB6B lipid modification to cell surface receptor trafficking.

    Evidence HMGCR inhibition, membrane fractionation, re-expression rescue of RAB6B and RAB27A together, cell growth assays in melanoma lines

    PMID:37277330

    Open questions at the time
    • Individual contribution of RAB6B versus RAB27A not resolved (dual rescue required)
    • Direct trafficking of specific integrins by RAB6B not shown
  9. 2024 High

    CNS-specific Rab6a/b double knockout demonstrated that RAB6 is required for axonal delivery of synaptic vesicle precursors and neuronal polarization, with DKO causing SVP accumulation near the Golgi, lysosome expansion, and severe cortical and cerebellar dysplasia.

    Evidence CNS-specific DKO mice, live imaging of SVP trafficking, immunofluorescence, and electron microscopy in cultured neurons

    PMID:38830762

    Open questions at the time
    • Mechanism of lysosome expansion in DKO neurons not defined
    • Whether RAB6B alone is essential or fully redundant with Rab6A in neurons remains unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The individual, non-redundant functions of RAB6B versus RAB6A remain undefined: single Rab6b knockout phenotypes have not been reported, and the specific cargoes, GAPs, and GEFs acting selectively on RAB6B are unknown.
  • No single Rab6b knockout phenotype reported
  • RAB6B-specific GEF and GAP not identified
  • Full cargo repertoire of RAB6B-positive vesicles uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 2
Localization
GO:0005794 Golgi apparatus 6 GO:0031410 cytoplasmic vesicle 5
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 4 R-HSA-1266738 Developmental Biology 2
Partners
BICD1DYNLRB1ELKS1GDAP1

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RAB6B is a Rab6 subfamily member that localizes to the Golgi apparatus and ERGIC-53-positive vesicles. It displays lower GTP-binding activity compared to Rab6A, and in overexpression distributes over both Golgi and ER membranes. The GTP-bound form (Q72L mutant) interacts with all known Rab6A effectors including Rabkinesin-6, suggesting a role in retrograde membrane traffic at the Golgi complex. cDNA cloning, immunofluorescence, northern blot, GTP-binding assays, overexpression of constitutively active mutant, co-localization studies Journal of cell science High 10893188
2006 Crystal structures of human neuronal RAB6B solved in the inactive (MgGDP-bound) and active (MgGTPγS-bound) forms at 2.3 Å and 1.8 Å resolution, respectively. Conformational changes between states occur mainly in switch I and switch II regions, and an additional change is observed in the Rab6 subfamily-specific RabSF3 region, which may contribute to effector specificity. X-ray crystallography Acta crystallographica. Section D, Biological crystallography High 16790928
2007 RAB6B interacts with Bicaudal-D1 (BICD1) in its GTP-bound (active) form, as shown by yeast two-hybrid, co-immunoprecipitation, and pull-down assays. RAB6B and BICD1 co-localize at the Golgi and along microtubule-aligned vesicles, and both co-localize with dynein in neurites of SK-N-SH neuronal cells. Live imaging showed bi-directional movement of EGFP-RAB6B structures in neurites, indicating RAB6B links to the dynein/dynactin complex via BICD1 to regulate retrograde transport in neuronal cells. Yeast two-hybrid, co-immunoprecipitation, pull-down assay, confocal microscopy, live-cell imaging Experimental cell research High 17707369
2008 RAB6B interacts with the dynein light chain DYNLRB1, as demonstrated by yeast two-hybrid, co-immunoprecipitation, and pull-down studies. Unlike Rab6A which preferentially binds DYNLRB1 in the GTP-bound state, RAB6B (and Rab6A') associates preferentially with DYNLRB1 in the GDP-bound state. DYNLRB1 co-localizes with RAB6B isoforms at the Golgi apparatus. Yeast two-hybrid, co-immunoprecipitation, pull-down assay, co-localization by fluorescence microscopy Cell motility and the cytoskeleton High 18044744
2013 RAB6B physically interacts with the outer mitochondrial membrane protein GDAP1 (mutated in Charcot-Marie-Tooth disease), placing RAB6B in a vesicle-organelle trafficking complex that may participate in mitochondrial movement within the cell. Co-immunoprecipitation/pull-down (interaction identified in GDAP1 silencing study) Neurobiology of disease Medium 23542510
2021 RAB6B is expressed in primary mouse macrophages where it localizes to the Golgi complex. Knockdown of Rab6b reduced TNF secretion by M. bovis BCG-infected macrophages without affecting Tnf mRNA or intracellular TNF protein levels, indicating RAB6B promotes post-translational trafficking and secretion of TNF in macrophages. siRNA knockdown, ELISA, qRT-PCR, Western blot, immunofluorescence/confocal microscopy Immunology and cell biology Medium 34555867
2022 Double knockout of RAB6A/A' and RAB6B in radial glial cells impairs apical localization of the apical determinant Crumbs3 (CRB3) and causes retraction of the apical process, leading to delamination and ectopic division of apical radial glia. RAB6+ post-Golgi vesicles move toward microtubule minus ends in an apical direction in a dynein-dependent manner, establishing a RAB6-dynein-LIS1 pathway for Golgi-to-apical-surface transport. Double KO mice/in utero electroporation, in situ subcellular live imaging, immunofluorescence, genetic epistasis with dynein activator LIS1 KO EMBO reports High 35979738
2023 The crystal structure of RAB6B in complex with the Rab6-binding domain of ELKS1 was solved, revealing that a C-terminal segment of ELKS1 forms a helical hairpin to recognize RAB6B through a unique binding mode. ELKS1 undergoes liquid-liquid phase separation (LLPS) that allows it to compete with other RAB6 effectors, accumulate RAB6B-coated liposomes, recruit RAB6B-coated vesicles to vesicle-releasing sites, and promote vesicle exocytosis. X-ray crystallography (co-crystal structure), in vitro reconstitution of LLPS, liposome binding assays, live-cell imaging of vesicle exocytosis The Journal of biological chemistry High 37172719
2023 Epigenetic suppression of PGC1α in BRAF-inhibitor-resistant melanomas reduces RAB6B and RAB27A expression. Statin (HMGCR inhibitor) treatment blocks cell growth by lowering RAB6B and RAB27A prenylation, which reduces their membrane association and impairs integrin localization and downstream integrin-FAK signaling. Re-expression of both RAB6B and RAB27A together reverses statin vulnerability. Pharmacological inhibition, re-expression rescue experiments, Western blot for membrane fractionation, cell growth assays Nature communications Medium 37277330
2024 CNS-specific Rab6a/b double knockout mice exhibit severe neocortical and cerebellar dysplasia. In cultured Rab6a/b DKO neurons, synaptic vesicle precursors (SVPs) abnormally accumulate adjacent to the Golgi apparatus, leading to defects in axonal extension and loss of axon-dendrite polarity. Rab6 DKO also causes significant lysosome expansion in neuronal soma, demonstrating that RAB6-mediated polarized transport of SVPs from the Golgi is essential for neuronal polarization and brain development. CNS-specific double knockout mice, live-cell imaging of vesicle trafficking, immunofluorescence, electron microscopy The Journal of neuroscience High 38830762
2019 miR-4268 directly targets RAB6B mRNA in gastric cancer cells. Silencing of RAB6B phenocopies miR-4268 overexpression, inhibiting cell proliferation and G1/S transition via suppression of AKT/JNK signaling pathways and modulation of Cyclin D1 and CDK4. Luciferase reporter assay (direct targeting), siRNA knockdown, cell cycle analysis, Western blot for AKT/JNK pathway Cancer gene therapy Medium 31303644
2023 miR-6216 directly targets RAB6B and negatively regulates its expression. Overexpression of miR-6216 inhibited neural stem cell (NSC) proliferation, while overexpression of RAB6B promoted NSC proliferation, placing RAB6B as a positive regulator of NSC proliferation downstream of miR-6216. miRNA overexpression, RAB6B overexpression, NSC proliferation assays Neuroscience research Low 37059126
2017 RAB6B was identified as a protein that co-immunoprecipitates with CEA (carcinoembryonic antigen) in LoVo colon cancer cells, suggesting a physical interaction between RAB6B and CEA. Co-immunoprecipitation followed by LC-MS/MS Radiation oncology journal Low 28881503

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus. Journal of cell science 105 10893188
2013 Silencing of the Charcot-Marie-Tooth disease-associated gene GDAP1 induces abnormal mitochondrial distribution and affects Ca2+ homeostasis by reducing store-operated Ca2+ entry. Neurobiology of disease 73 23542510
2008 Rab6 family proteins interact with the dynein light chain protein DYNLRB1. Cell motility and the cytoskeleton 64 18044744
2007 A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Experimental cell research 56 17707369
2019 Genome-wide association study of birth weight in sheep. Animal : an international journal of animal bioscience 51 30616710
2012 ATP induces protein arginine deiminase 2-dependent citrullination in mast cells through the P2X7 purinergic receptor. Journal of immunology (Baltimore, Md. : 1950) 42 22984079
2000 Expression of Rab small GTPases in epithelial Caco-2 cells: Rab21 is an apically located GTP-binding protein in polarised intestinal epithelial cells. European journal of cell biology 37 10887961
2022 RAB6 and dynein drive post-Golgi apical transport to prevent neuronal progenitor delamination. EMBO reports 33 35979738
2017 On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addiction biology 27 28247455
2020 Somatic variants in new candidate genes identified in focal cortical dysplasia type II. Epilepsia 23 32216069
2019 MicroRNA-4268 inhibits cell proliferation via AKT/JNK signalling pathways by targeting Rab6B in human gastric cancer. Cancer gene therapy 19 31303644
2014 Effects of dechlorane plus on the hepatic proteome of juvenile Chinese sturgeon (Acipenser sinensis). Aquatic toxicology (Amsterdam, Netherlands) 19 24463492
2013 Rab41 is a novel regulator of Golgi apparatus organization that is needed for ER-to-Golgi trafficking and cell growth. PloS one 19 23936529
2023 Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas. Nature communications 18 37277330
2016 ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles. Journal of cell science 18 27550519
2014 Identification of core miRNA based on small RNA-seq and RNA-seq for colorectal cancer by bioinformatics. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 25412953
2006 The structure of human neuronal Rab6B in the active and inactive form. Acta crystallographica. Section D, Biological crystallography 14 16790928
2022 Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p. Journal of neuro-oncology 12 36094613
2023 Structural basis of ELKS/Rab6B interaction and its role in vesicle capturing enhanced by liquid-liquid phase separation. The Journal of biological chemistry 11 37172719
2023 Integrated transcriptome and proteome analysis indicates potential biomarkers of prostate cancer in offspring of pregnant rats exposed to a phthalate mixture during gestation and lactation. Chemosphere 10 37690569
2021 A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy. International journal of molecular sciences 10 34281234
2023 Insight on the hub gene associated signatures and potential therapeutic agents in epilepsy and glioma. Brain research bulletin 9 37192718
2021 Rab6b localizes to the Golgi complex in murine macrophages and promotes tumor necrosis factor release in response to mycobacterial infection. Immunology and cell biology 8 34555867
2007 Transcriptomic comparison of human hepatoma Huh-7 cell clones with different hepatitis C virus replication efficiencies. Japanese journal of infectious diseases 6 17642525
2022 Genome variation in tick infestation and cryptic divergence in Tunisian indigenous sheep. BMC genomics 4 35227193
2021 Autoantibody against the Rab6A/Rab6B in primary autoimmune cerebellar ataxia associated with Sjogren's syndrome: A case report. Journal of neuroimmunology 4 34332492
2025 Protein Alterations in Patients with Delirium after Cardiac Surgery: An Exploratory Case-Control Substudy of the VISION Cardiac Surgery Biobank. Anesthesiology 3 39786937
2024 Rab6-Mediated Polarized Transport of Synaptic Vesicle Precursors Is Essential for the Establishment of Neuronal Polarity and Brain Formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 3 38830762
2023 miR-6216 regulates neural stem cell proliferation by targeting RAB6B. Neuroscience research 3 37059126
2024 A comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine. Proceedings of the National Academy of Sciences of the United States of America 2 39475639
2017 Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation. Radiation oncology journal 2 28881503
2025 Risk relationship between osteoporosis and plasma proteins. Medicine 1 40898453
2025 Integrative eQTL and Mendelian randomization analysis reveals key genes in colorectal cancer. Discover oncology 0 41252059