Affinage

RAB6B

Ras-related protein Rab-6B · UniProt Q9NRW1

Length
208 aa
Mass
23.5 kDa
Annotated
2026-06-10
33 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB6B is a brain-enriched small GTPase of the Golgi apparatus and post-Golgi vesicles that cycles between GDP- and GTP-bound conformations, with switch I/II and the RAB6 subfamily-specific RabSF3 region governing effector engagement and isoform specificity (PMID:10893188, PMID:16790928). In its active GTP-bound state it recruits effectors that couple vesicles to the dynein/dynactin retrograde motor machinery, binding Bicaudal-D1 (BICD1) at the Golgi and along microtubules and engaging the dynein light chain DYNLRB1, thereby directing bi-directional vesicle movement in neurites (PMID:17707369, PMID:18044744). RAB6B-coated vesicles move toward microtubule minus ends in a dynein-dependent manner, and ELKS1 captures these vesicles into liquid-liquid phase-separated condensates—via a unique C-terminal helical-hairpin binding mode—to deliver them to release sites and promote exocytosis (PMID:35979738, PMID:37172719). In the developing nervous system RAB6B acts redundantly with RAB6A/A': combined loss disrupts apical CRB3 localization and the RAB6–dynein–LIS1-dependent Golgi-to-apical-surface transport that maintains radial glial progenitors, and causes accumulation of synaptic vesicle precursors at the Golgi with failure of polarized axonal transport, producing neocortical and cerebellar dysplasia and loss of axon–dendrite polarity (PMID:35979738, PMID:38830762). Outside the brain, RAB6B positively regulates TNF vesicle trafficking and secretion in infected macrophages without altering Tnf transcription (PMID:34555867), and its membrane association requires prenylation, linking it to integrin localization and FAK signaling (PMID:37277330). RAB6B expression is repressed by miR-4268 and miR-6216, and modulating its levels alters cell proliferation through AKT/JNK signaling and Cyclin D1/CDK4 (PMID:31303644, PMID:37059126).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Established RAB6B as a brain-restricted RAB6 paralog distinct from ubiquitous RAB6A, defining its Golgi/ER localization, weaker GTP-binding, and capacity to share RAB6A effectors—framing a cell-type-specific role in Golgi membrane traffic.

    Evidence Subcellular fractionation, immunofluorescence, immunohistochemistry, and GTP-locked Q72L mutant co-IP with effectors

    PMID:10893188

    Open questions at the time
    • Did not resolve which effectors are functionally relevant in neurons
    • No in vivo functional consequence tested
  2. 2006 High

    Solved the structural basis of RAB6B nucleotide switching, localizing conformational change to switch I/II and identifying the RabSF3 region as a candidate determinant of RAB6 isoform effector specificity.

    Evidence X-ray crystallography of GDP-bound (2.3 Å) and GTPγS-bound (1.8 Å) RAB6B

    PMID:16790928

    Open questions at the time
    • RabSF3 contribution to specificity inferred from structure, not validated by effector-binding mutagenesis
    • No effector co-structure in this study
  3. 2007 High

    Connected active RAB6B to the dynein retrograde transport machinery in neuronal cells by identifying GTP-dependent binding to BICD1 and co-localization with dynein in neurites.

    Evidence Yeast two-hybrid, reciprocal Co-IP, pull-down, confocal co-localization, and live imaging of EGFP-RAB6B in SK-N-SH cells

    PMID:17707369

    Open questions at the time
    • Cargo transported via RAB6B-BICD1 not defined
    • Functional requirement of the interaction not tested by loss-of-function
  4. 2008 High

    Refined the motor coupling by showing RAB6B binds the dynein light chain DYNLRB1 preferentially in the GDP state and that DYNLRB1 is not a GAP, distinguishing structural motor association from nucleotide regulation.

    Evidence Yeast two-hybrid, Co-IP, pull-down, co-localization, and in vitro GTPase assay

    PMID:18044744

    Open questions at the time
    • Physiological role of nucleotide-state-dependent DYNLRB1 binding unresolved
    • GDP-preference versus GTP-dependent BICD1 binding not mechanistically reconciled
  5. 2021 Medium

    Extended RAB6B function beyond the nervous system by establishing it as a positive regulator of TNF vesicle secretion in macrophages, acting at the trafficking step rather than transcription.

    Evidence siRNA knockdown with ELISA, qRT-PCR, and intracellular flow cytometry in BCG-infected primary mouse macrophages

    PMID:34555867

    Open questions at the time
    • Effectors mediating TNF vesicle transport not identified
    • Single lab; specific Golgi-to-surface route not mapped
  6. 2022 High

    Demonstrated in vivo that RAB6A/B redundantly drive dynein-dependent minus-end-directed transport of post-Golgi vesicles delivering polarity determinant CRB3 to the apical surface, integrating RAB6 into a RAB6–dynein–LIS1 complex maintaining radial glial progenitors.

    Evidence Conditional Rab6a/a' and Rab6b double knockout, in situ live imaging, CRB3 immunofluorescence, and LIS1-KO phenocopy

    PMID:35979738

    Open questions at the time
    • Individual contribution of RAB6B versus RAB6A not separated
    • Direct biochemical link of RAB6 to LIS1 not shown
  7. 2023 High

    Provided the structural and biophysical mechanism by which ELKS1 captures RAB6B vesicles, showing a unique helical-hairpin binding mode and phase-separation-driven competition that concentrates RAB6B-coated vesicles at release sites for exocytosis.

    Evidence X-ray co-crystal structure, in vitro LLPS and liposome-condensate co-sedimentation, mutagenesis, and live-cell exocytosis assay

    PMID:37172719

    Open questions at the time
    • In vivo requirement of ELKS1-RAB6B condensates not tested
    • Competition hierarchy among RAB6 effectors in cells not quantified
  8. 2024 High

    Established the in vivo neurodevelopmental requirement: RAB6 (including RAB6B) is needed for polarized anterograde Golgi-to-axon transport of synaptic vesicle precursors, with loss causing SVP accumulation, axon-dendrite polarity failure, and neocortical/cerebellar dysplasia.

    Evidence CNS-specific conditional Rab6a/b double KO mice, primary neuron deletion, polarity/SVP marker immunofluorescence, and EM of lysosomal expansion

    PMID:38830762

    Open questions at the time
    • RAB6B-specific role versus RAB6A redundancy not dissected
    • Mechanism linking transport block to lysosomal expansion unresolved
  9. 2023 Medium

    Linked RAB6B membrane targeting to prenylation, showing statin-mediated loss of prenylation reduces membrane association and affects integrin localization and FAK signaling in drug-resistant melanoma.

    Evidence Statin treatment, membrane fractionation, and RAB6B+RAB27A re-expression rescue with integrin/FAK readouts

    PMID:37277330

    Open questions at the time
    • Direct enzymology of RAB6B prenylation not characterized
    • RAB6B-specific contribution separable from RAB27A only partially resolved
  10. 2019 Medium

    Implicated RAB6B in proliferative control, showing its silencing suppresses AKT/JNK signaling and G1/S transition and that miR-4268 directly targets it.

    Evidence siRNA knockdown, luciferase reporter, cell cycle analysis, and pathway western blots in gastric cancer cells

    PMID:31303644

    Open questions at the time
    • Mechanistic link between a trafficking GTPase and AKT/JNK signaling not defined
    • Single cancer cell context
  11. 2023 Medium

    Added a second regulatory miRNA, showing miR-6216 directly represses RAB6B and that RAB6B levels bidirectionally control neural stem cell proliferation.

    Evidence Luciferase 3'UTR reporter, RAB6B and miR-6216 overexpression, and NSC proliferation assays

    PMID:37059126

    Open questions at the time
    • Downstream pathway from RAB6B to NSC proliferation not mapped
    • Single lab; in vivo relevance untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether RAB6B has non-redundant, isoform-specific functions distinct from RAB6A in neurons and other tissues, and how its distinct effectors (BICD1, DYNLRB1, ELKS1) are coordinated on individual vesicles, remains unresolved.
  • No RAB6B-single-knockout phenotype reported in the corpus
  • Spatiotemporal hierarchy of effector recruitment per vesicle not defined
  • Mechanism connecting RAB6B trafficking to AKT/JNK proliferative signaling unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3
Localization
GO:0005794 Golgi apparatus 3 GO:0031410 cytoplasmic vesicle 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1266738 Developmental Biology 2 R-HSA-9609507 Protein localization 2
Complex memberships
RAB6-dynein-LIS1 complex

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RAB6B localizes to the Golgi apparatus and ERGIC-53-positive vesicles. Unlike the ubiquitously expressed RAB6A, RAB6B shows cell-type-specific expression predominantly in brain (microglia, pericytes, Purkinje cells) and neuroblastoma cells. RAB6B displays lower GTP-binding activities than RAB6A and in overexpression distributes over both Golgi and ER membranes, whereas RAB6A is more restricted to Golgi. The GTP-bound form (Q72L mutant) interacts with all known RAB6A effectors including Rabkinesin-6, suggesting a cell-type-specific role in retrograde membrane traffic at the Golgi complex. Subcellular fractionation, immunofluorescence, northern blot, immunohistochemistry, overexpression of GTP-locked mutant (Q72L), co-immunoprecipitation with effectors Journal of cell science High 10893188
2007 RAB6B interacts with Bicaudal-D1 (BICD1) in its GTP-bound (active) form. RAB6B and BICD1 co-localize at the Golgi and on vesicles aligning along microtubules, and both co-localize with dynein in neurites of SK-N-SH neuronal cells. Live cell imaging revealed bi-directional movement of EGFP-RAB6B structures in neurites. This places RAB6B, via BICD1, in the dynein/dynactin retrograde transport complex in neuronal cells. Yeast two-hybrid screen, co-immunoprecipitation, pull-down assays, confocal co-localization, live cell imaging (EGFP-RAB6B) Experimental cell research High 17707369
2008 RAB6B directly interacts with the dynein light chain DYNLRB1. Pull-down experiments showed a preferred association of DYNLRB1 with GDP-bound RAB6B (and GDP-bound RAB6A'), in contrast to GTP-bound RAB6A. DYNLRB1 co-localizes with all three RAB6 isoforms at the Golgi. In vitro GTPase activity assays showed DYNLRB1 does NOT stimulate RAB6 GTPase activity. Yeast two-hybrid, co-immunoprecipitation, pull-down assays, immunofluorescence co-localization, in vitro GTPase activity assay Cell motility and the cytoskeleton High 18044744
2006 Crystal structures of human neuronal RAB6B were solved in the GDP-bound ('inactive', 2.3 Å) and GTPγS-bound ('active', 1.8 Å) forms. Conformational changes between states are concentrated in the switch I and switch II regions. Additional changes were observed in the RAB6 subfamily-specific RabSF3 region, potentially contributing to effector specificity of RAB6 isoforms. X-ray crystallography (space group P2₁2₁2₁; 2.3 Å GDP-bound and 1.8 Å GTPγS-bound structures) Acta crystallographica. Section D, Biological crystallography High 16790928
2013 RAB6B physically interacts with GDAP1 (an outer mitochondrial membrane protein implicated in Charcot-Marie-Tooth disease) and with caytaxin, suggesting RAB6B participates in mitochondrial movement within the cell. Co-immunoprecipitation (interaction between GDAP1 and RAB6B/caytaxin in SH-SY5Y cells) Neurobiology of disease Low 23542510
2021 RAB6B is expressed in primary mouse macrophages and localizes to the Golgi complex. Mycobacterium bovis BCG infection dynamically alters RAB6B expression in macrophages in vitro and in vivo. RAB6B knockdown reduces TNF secretion from BCG-infected macrophages without affecting Tnf mRNA levels or intracellular TNF protein abundance, establishing RAB6B as a positive regulator of TNF vesicle trafficking and secretion in macrophages. Immunofluorescence localization, siRNA knockdown, ELISA (TNF secretion), qRT-PCR (Tnf mRNA), intracellular flow cytometry (TNF protein), in vivo infection model Immunology and cell biology Medium 34555867
2022 Double knockout of RAB6A/A' and RAB6B in radial glial (aRG) neural progenitors impairs apical localization of the polarity determinant CRB3 (Crumbs3) and induces retraction of the aRG apical process, leading to delamination and ectopic division. Live imaging showed RAB6+ post-Golgi vesicles move toward microtubule minus ends in a dynein-dependent manner. RAB6-dynein-LIS1 constitute a complex required for Golgi-to-apical-surface transport in aRG cells. In situ subcellular live imaging, RAB6A/A' and RAB6B double knockout (conditional KO mice/organoids), immunofluorescence for CRB3 apical localization, LIS1 knockout phenocopy, co-localization studies EMBO reports High 35979738
2023 ELKS1 binds RAB6B through a C-terminal helical hairpin segment that engages RAB6B via a unique binding mode (co-crystal structure solved). Liquid-liquid phase separation (LLPS) of ELKS1 allows it to compete with other RAB6 effectors for RAB6B binding and accumulate RAB6B-coated liposomes into ELKS1 condensates. ELKS1 condensates recruit RAB6B-coated vesicles to vesicle-releasing sites and promote vesicle exocytosis. X-ray co-crystal structure of RAB6B–ELKS1 Rab6-binding domain complex, in vitro LLPS assay, liposome-condensate co-sedimentation, live cell vesicle exocytosis assay, mutagenesis The Journal of biological chemistry High 37172719
2024 CNS-specific Rab6a/b double knockout (DKO) mice exhibit severe dysplasia of the neocortex and cerebellum. In Rab6 DKO neurons, synaptic vesicle precursors (SVPs) abnormally accumulate adjacent to the Golgi apparatus, causing defects in axonal extension and loss of axon-dendrite polarity. RAB6 DKO also causes significant lysosomal expansion in the soma. This establishes Rab6 (including Rab6b) as required for polarized anterograde transport of SVPs from the Golgi to the axon during neuronal polarity establishment. CNS-specific conditional Rab6a/b double KO mice (both sexes), in vitro primary neuron culture with Rab6a/b deletion, immunofluorescence for SVP markers and polarity markers, electron microscopy (lysosome expansion) The Journal of neuroscience High 38830762
2023 Statin treatment (HMGCR inhibition) reduces RAB6B prenylation, which decreases RAB6B membrane association and affects integrin localization and downstream FAK signaling required for cell growth in PGC1α-suppressed BRAF-inhibitor-resistant melanoma cells. Combined re-expression of RAB6B and RAB27A reverses statin vulnerability in these cells. Pharmacological statin treatment, membrane fractionation (prenylation/membrane association), rescue by RAB6B+RAB27A re-expression, integrin localization immunofluorescence, FAK signaling western blot Nature communications Medium 37277330
2019 RAB6B silencing in gastric cancer cells inhibits cell proliferation and G1/S transition through suppression of AKT/JNK signaling pathways, leading to reduced Cyclin D1 and CDK4 levels. miR-4268 directly targets RAB6B mRNA and phenocopies RAB6B silencing. siRNA-mediated RAB6B knockdown, luciferase reporter assay (miR-4268 targeting), cell cycle analysis, western blot (AKT/JNK/p38 pathway, Cyclin D1, CDK4), proliferation assays Cancer gene therapy Medium 31303644
2023 miR-6216 directly targets and negatively regulates RAB6B expression in neural stem cells (NSCs). Overexpression of RAB6B promotes NSC proliferation, whereas forced overexpression of miR-6216 inhibits NSC proliferation. Luciferase reporter assay (miR-6216 targeting of RAB6B 3'UTR), RAB6B overexpression, miR-6216 overexpression, NSC proliferation assays Neuroscience research Medium 37059126
2017 RAB6B was identified as a protein that co-immunoprecipitates with CEA (carcinoembryonic antigen) in LoVo colon cancer cells. RAB6B expression was down-regulated in LoVo cells in a radiation dose-dependent manner. Anti-CEA immunoprecipitation followed by LC-MS/MS mass spectrometry; western blot post-irradiation 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 52 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 28 28247455
2020 Somatic variants in new candidate genes identified in focal cortical dysplasia type II. Epilepsia 24 32216069
2023 Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas. Nature communications 20 37277330
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
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 13 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
2025 Protein Alterations in Patients with Delirium after Cardiac Surgery: An Exploratory Case-Control Substudy of the VISION Cardiac Surgery Biobank. Anesthesiology 4 39786937
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
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
2017 Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation. Radiation oncology journal 3 28881503
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
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

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