Affinage

RAB3D

Ras-related protein Rab-3D · UniProt O95716

Length
219 aa
Mass
24.3 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB3D is a geranylgeranylated small GTPase that governs the maturation and regulated exocytosis of secretory granules across multiple secretory cell types, where it is anchored to granule membranes via its isoprenylated, reversibly carboxyl-methylated C-terminus (PMID:8738417, PMID:8843780, PMID:9716267). It associates with secretory granules in pancreatic acinar, mast, and neuroendocrine cells and participates in the GTP-dependent step of regulated secretion, with secretagogue stimulation enhancing GTP loading and release from the granule membrane, an event tightly coupled to actin coating of granules during exocytosis (PMID:9399951, PMID:10655489). Genetic loss of RAB3D produces enlarged secretory granules in exocrine glands without altering secretion kinetics, establishing a primary role in granule maturation—limiting granule size and controlling cargo composition rather than executing the final fusion step (PMID:12192047, PMID:23526941). On individual vesicles RAB3D occupies microdomains in defined proportion with RAB27 isoforms, and this balance tailors secretory cargo such as cathepsin S (PMID:27076615). RAB3D acts through nucleotide-state-dependent partners: it binds the cargo receptor pIgR in the GDP-bound state and dissociates upon stimulation (PMID:18171724), recruits the dynein light chain Tctex-1 in a GTP-dependent manner to drive vesicle transport to the osteoclast ruffled border during bone resorption (PMID:15923639, PMID:21262767), and engages calmodulin in a calcium-dependent manner at the osteoclast plasma membrane (PMID:27897225). At the Golgi, RAB3D is required for COPI vesiculation and maintains Golgi architecture as part of a complex with GOLGA4 and MYH10, its loss triggering Golgi fragmentation and GOLGA4-mediated Golgiphagy (PMID:34494400, PMID:38591519). RAB3D transcription is directly activated by MIST1 and c-MYC (PMID:20038531, PMID:36280757), and in cancer contexts it is induced downstream of AhR and RHOF/AMPK signaling, where it activates PI3K/AKT/GSK3β signaling to promote migration, invasion, and EMT (PMID:25823663, PMID:33205519, PMID:36153645).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Establishing where RAB3D acts: defining its subcellular home was the first step toward assigning a function, and it was localized specifically to secretory granule membranes via an isoprenyl anchor.

    Evidence Western blot, immunofluorescence, immunoelectron microscopy and Triton X-114 partitioning in rat pancreatic acinar cells

    PMID:8738417 PMID:8843780

    Open questions at the time
    • Does not establish what step of secretion RAB3D controls
    • Membrane-anchoring mechanism inferred from detergent partitioning, not direct lipid analysis
  2. 1997 High

    Linking RAB3D to a functional step: overexpression and stimulation experiments showed RAB3D operates at the GTP-dependent step of regulated exocytosis, with opposite directional effects in different cell types.

    Evidence Transgenic mouse overexpression and GTP-binding assays in pancreas (enhanced secretion); mutant overexpression in RBL-2H3 mast cells (inhibited degranulation)

    PMID:9300704 PMID:9399951

    Open questions at the time
    • Opposite phenotypes across cell types unresolved
    • No direct effector identified at this stage
  3. 1998 Medium

    Distinguishing the step controlled: dominant-negative RAB3D blocked granule positioning and mature-product secretion without affecting cargo processing, separating a trafficking/docking role from biosynthetic steps.

    Evidence Stable dominant-negative N135I expression in AtT-20 neuroendocrine cells with ACTH secretion and fractionation assays; carboxyl-methylation characterized by 2D gel/IEF and inhibitors

    PMID:9442106 PMID:9716267

    Open questions at the time
    • Methylation does not affect membrane association, so its functional consequence remained unclear
    • Single dominant-negative mutant may have off-target effects on related Rabs
  4. 1999 Medium

    Tracking dynamic behavior: imaging of post-exocytotic translocation and discovery that RAB3D is delivered by REP rather than cycling via GDI refined the model of how RAB3D engages and leaves membranes.

    Evidence Confocal imaging of mast cell degranulation; gel filtration and in vitro geranylgeranylation in gastric chief cells

    PMID:10022613 PMID:9870920

    Open questions at the time
    • REP-versus-GDI distinction shown in one cell type only
    • Functional significance of plasma membrane retention after exocytosis unknown
  5. 2000 Medium

    Connecting RAB3D dynamics to granule machinery and cargo: RAB3D release was coupled to actin coating of granules, RAB3D promoted granule docking, and it was found on cargo-specific transcytotic vesicles.

    Evidence Confocal imaging with GTPγS/actomyosin modulation in acini; quantitative EM in PC12 cells; anti-RAB3D vesicle immunoisolation in hepatocytes

    PMID:10655489 PMID:10915742 PMID:11208087

    Open questions at the time
    • Causal link between RAB3D release and actin polymerization not biochemically resolved
    • Cargo selectivity mechanism for transcytotic vesicles unknown
  6. 2001 Medium

    Identifying a downstream effector: a RAB3D-associated Ser/Thr kinase (Rak3D) phosphorylating syntaxin 4 provided a mechanistic bridge from RAB3D to calcium-dependent SNARE complex assembly.

    Evidence Co-immunoprecipitation, in vitro kinase assay, and syntaxin 4–SNAP23 binding assays in RBL-2H3 mast cells

    PMID:11555639

    Open questions at the time
    • Molecular identity of Rak3D kinase not established
    • Co-IP without reciprocal validation of direct RAB3D–kinase binding
  7. 2002 High

    Resolving the core function genetically: knockout mice showed RAB3D is dispensable for the final fusion step but required to limit granule size, redefining its role as a regulator of granule maturation.

    Evidence RAB3D knockout mouse morphometry and secretion/capacitance assays; adenoviral dominant-negative mutants in pancreatic acini

    PMID:11875077 PMID:12192047

    Open questions at the time
    • Mechanism by which RAB3D prevents granule enlargement (e.g. homotypic fusion) not defined
    • Discrepancy between dominant-negative secretion defects and KO normal kinetics unexplained
  8. 2003 High

    Clarifying dominant-negative mechanism and tissue-specific behavior: dominant-negative RAB3D acts by sequestering GEF activity, and RAB3D shows nucleotide-dependent membrane recruitment with cell-type-specific inhibitory versus stimulatory roles.

    Evidence Rim1 effector affinity precipitation and fractionation in acini; isoproterenol-stimulated fractionation and permeabilized parotid acini assays

    PMID:14522985 PMID:14566969

    Open questions at the time
    • Identity of the RAB3D GEF not determined
    • Basis for inhibitory role in parotid versus stimulatory role in pancreas unresolved
  9. 2005 High

    Extending RAB3D to a new physiological process: RAB3D was shown to control a post-TGN trafficking step required for osteoclastic bone resorption, broadening its role beyond classical exocytosis.

    Evidence RAB3D knockout skeletal/ultrastructural analysis, mutant overexpression, and in vitro bone resorption assays in osteoclasts

    PMID:15923639

    Open questions at the time
    • Effectors driving the post-TGN step not identified at this stage
    • Link between vesicle delivery and ruffled border formation mechanistic detail incomplete
  10. 2008 High

    Identifying a direct cargo-receptor partner: RAB3D was shown to bind pIgR directly in a GDP-state-specific manner, providing a molecular handle for how RAB3D selects cargo.

    Evidence Pull-down with recombinant RAB3D variants, blot overlay, and dominant-negative secretion assays in lacrimal acinar cells

    PMID:18171724

    Open questions at the time
    • Whether pIgR binding is direct or bridged not fully resolved despite blot overlay
    • Single cell-type and lab
  11. 2009 High

    Establishing transcriptional control: MIST1 was shown to directly activate RAB3D transcription, coupling secretory-cell differentiation programs to granule machinery expression.

    Evidence ChIP of E-box binding, Mist1 knockout qRT-PCR, and granule-formation reporter assays with RAB inhibitors

    PMID:20038531

    Open questions at the time
    • Other transcriptional inputs not addressed
    • Direct contribution of RAB3D versus RAB26 to granule formation not separated
  12. 2011 High

    Identifying a GTP-dependent transport effector: Tctex-1 dynein light chain was found to link active RAB3D vesicles to the microtubule motor, explaining how RAB3D vesicles reach the osteoclast ruffled border.

    Evidence Yeast two-hybrid, co-IP, vesicle colocalization, dynein pulldown, and RNAi bone resorption assays in osteoclasts

    PMID:21262767

    Open questions at the time
    • Whether Tctex-1 binding is the sole transport mechanism unknown
    • Single lab
  13. 2013 Medium

    Defining the maturation function molecularly: dominant-negative RAB3D blocked furin removal and prohormone processing, showing RAB3D is required for immature granule maturation and cortical positioning.

    Evidence Dominant-negative N135I expression in PC12 cells with furin retention and secretogranin II processing assays

    PMID:23526941

    Open questions at the time
    • Effector mediating furin removal not identified
    • Single dominant-negative approach
  14. 2015 Medium

    Opening a disease/pathological dimension: RAB3D was shown to drive cancer cell motility and EMT through AKT/GSK3β signaling and Hsp90α secretion, repurposing its trafficking role in tumor biology.

    Evidence siRNA knockdown, migration/invasion assays, orthotopic mouse metastasis model, and pathway readouts

    PMID:25823663

    Open questions at the time
    • Mechanistic link between RAB3D GTPase activity and AKT activation unclear
    • Whether secretory function underlies oncogenic phenotype not separated
  15. 2016 High

    Refining vesicle-level regulation and adding a calcium effector: super-resolution imaging showed RAB3D/RAB27 microdomain balance tailors cargo, and calmodulin was identified as a calcium-dependent RAB3D partner controlling resorption.

    Evidence Dual KO mice with 3D-SIM and CTSS secretion assays; yeast two-hybrid, BRET, and calmodulin-blockade resorption assays in osteoclasts

    PMID:27076615 PMID:27897225

    Open questions at the time
    • How RAB3D/RAB27 ratio is set on individual vesicles unknown
    • Calmodulin binding site on RAB3D not mapped
  16. 2021 High

    Establishing a Golgi-intrinsic role and additional regulation: RAB3D was shown to be required for COPI vesiculation and Golgi integrity, and its expression to be controlled post-transcriptionally via RHOF/AMPK signaling.

    Evidence RAB3D KO mice/cells, COPI vesiculation assays, ER-stress markers, and human ALD tissue; RHOF–AMPK co-IP and RAB3D mRNA stability assays in HCC

    PMID:33205519 PMID:34494400

    Open questions at the time
    • Mechanism coupling RAB3D to COPI machinery not defined
    • How AMPK affects RAB3D mRNA stability molecularly unknown
  17. 2022 Medium

    Mapping additional transcriptional and protein-stability circuits: AhR and c-MYC were shown to drive RAB3D transcription, and RAB3D to stabilize MDM2, embedding it in oncogenic signaling loops.

    Evidence AhR KD/OE with PI3K inhibitor rescue in prostate cancer; c-MYC ChIP and MDM2 ubiquitination/β-catenin assays in AML

    PMID:36153645 PMID:36280757

    Open questions at the time
    • Direct biochemical link between RAB3D and MDM2 stabilization not resolved
    • Whether RAB3D trafficking function is required for these oncogenic effects unclear
  18. 2024 High

    Defining the structural Golgi complex and a degradation pathway: RAB3D forms a GOLGA4–MYH10 complex maintaining Golgi architecture, and its loss triggers GOLGA4-mediated Golgiphagy.

    Evidence Co-IP, proximity ligation, structured illumination microscopy, RAB3D KO/KD with autophagy markers and hydroxychloroquine rescue in hepatocytes

    PMID:38591519

    Open questions at the time
    • Whether RAB3D GTPase cycling regulates the GOLGA4–MYH10 complex unknown
    • Connection between this Golgi-maintenance role and granule maturation role not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GTPase reconciles its roles—granule maturation/size control, post-TGN/COPI vesicle trafficking, cargo selection via RAB27 balance, and Golgi structural maintenance—through a unifying biochemical mechanism and a defined GEF remains unresolved.
  • No RAB3D-specific GEF identified across the corpus
  • No structural model linking nucleotide state to its distinct effector engagements
  • Whether oncogenic signaling roles are mechanistically separable from secretory/trafficking functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0005198 structural molecule activity 3
Localization
GO:0005794 Golgi apparatus 4 GO:0031410 cytoplasmic vesicle 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-9612973 Autophagy 1
Partners
CALMGOLGA4MYH10PIGRRAB27REP/CHMTCTEX1/DYNLT1
Complex memberships
RAB3D–GOLGA4–MYH10 trans-Golgi complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Rab3D localizes exclusively to zymogen granule membranes in rat pancreatic acinar cells, as demonstrated by Western blotting, immunocytochemistry, and electron microscopic immunogold labeling; the majority of Rab3D is membrane-associated and likely anchored via isoprenyl groups (partitions into detergent phase in Triton X-114 extractions). Western blot, confocal immunofluorescence, immunoelectron microscopy, Triton X-114 phase partitioning European journal of cell biology High 8738417 8843780
1997 Overexpression of Rab3D in transgenic mouse pancreatic acinar cells enhances secretagogue-stimulated amylase release (160% of control at low CCK dose); CCK stimulation of permeabilized acini increases GTP incorporation into HA-tagged Rab3D, indicating Rab3D participates in the GTP-dependent step of regulated exocytosis. Transgenic mouse overexpression, amylase secretion assay, radiolabeled GTP binding assay in permeabilized acini The Journal of clinical investigation High 9399951
1997 In RBL-2H3 mast cells, Rab3D is predominantly membrane-associated (unlike Rab3A which is cytosolic); overexpression of wild-type or GTP-binding-deficient (N135I) Rab3D inhibits FcεRI-triggered degranulation (beta-hexosaminidase release) by ~2-fold, implicating Rab3D in a rate-limiting step of IgE-receptor-stimulated exocytosis. Subcellular fractionation, beta-hexosaminidase release assay, stable transfection of wild-type and mutant Rab3D Journal of immunology Medium 9300704
1998 Expression of dominant-negative Rab3D N135I in AtT-20 neuroendocrine cells inhibits positioning of dense core granules near the plasma membrane, blocks regulated secretion of mature ACTH, and impairs membrane association of Rab3A, without affecting ACTH precursor processing or packaging into granules. Stable transfection of mutant Rab3D, ACTH secretion assay, immunocytochemistry, cell fractionation The Journal of cell biology Medium 9442106
1998 Rab3D undergoes reversible carboxyl-methylation on its C-terminal prenylcysteine residue by a geranylgeranyl-specific methyltransferase; methylation state correlates inversely with secretory competence during pancreatic development (fetal/secretory-incompetent glands have predominantly methylated Rab3D; neonatal/adult secretory-competent glands have ~50% methylated), but methylation does not affect membrane association. 2D SDS-PAGE/IEF, isoelectric focusing, developmental Western blot analysis, inhibitor studies (N-acetyl-S-geranylgeranyl-L-cysteine, lovastatin) European journal of cell biology Medium 9716267
1999 Rab3D localizes to secretory granules in mast cells (full colocalization in mature peritoneal mast cells); following exocytotic degranulation, Rab3D translocates to the plasma membrane where it remains for at least 15 min, identifying a post-exocytosis fate distinct from the synaptic vesicle cycle. Immunoblot (Northern and RNase protection for isoform identification), immunofluorescence, confocal microscopy in resting and stimulated mast cells American journal of respiratory cell and molecular biology Medium 9870920
1999 In gastric chief cells (unlike neurons/brain), cytosolic Rab3D is complexed with Rab escort protein (REP), not Rab-GDI, as shown by gel filtration chromatography; in vitro assays show Rab3D remains associated with REP after geranylgeranylation, suggesting REP delivers Rab3D to its target membrane rather than Rab3D cycling via GDI. Gel filtration chromatography, co-fractionation, in vitro geranylgeranylation assay Journal of cellular biochemistry Medium 10022613
2000 During regulated exocytosis in pancreatic acinar cells, a subpopulation of zymogen granules near the apical membrane acquires filamentous actin coating; these actin-coated granules lack Rab3D, and the loss of Rab3D is prevented by GTPγS or actomyosin-modulating agents, indicating that Rab3D release from granule membranes is tightly coupled to actin polymerization around secretory granules. Confocal immunofluorescence, carbamylcholine-stimulated exocytosis, pharmacological modulation (GTPγS, actomyosin inhibitors) Proceedings of the National Academy of Sciences of the United States of America Medium 10655489
2000 In rat hepatocytes (constitutive secretory cells), Rab3D is enriched in transcytotic carrier vesicles; vesicles immunoisolated with anti-Rab3D antibody are enriched in the transcytosed form of polymeric IgA receptor (pIgA-R) but lack Golgi markers or pIgA-R precursor. Cholestasis causes Rab3D accumulation in pericanalicular cytoplasm, correlating with slowed transcytosis. RT-PCR, immunoblot, indirect immunofluorescence, anti-Rab3D immunoisolation of vesicles, bile duct ligation model Hepatology Medium 10915742
2000 In PC12 cells, expression of wild-type Rab3A or Rab3D increases the total number of secretory granules and the fraction docked at the plasma membrane; expression of dominant-negative Rab3D N135I decreases both parameters. Immunoelectron microscopy shows Rab3A and Rab3D can coexist on the same granule before and after docking. Electron microscopy of transfected PC12 cells, quantitative morphometry, immunoelectron microscopy Traffic Medium 11208087
2001 A Ser/Thr kinase activity (Rak3D) co-immunoprecipitates specifically with Rab3D in RBL-2H3 mast cells; Rak3D activity is maximal in resting cells and decreases upon FcεRI stimulation in a calcium-dependent manner. Rak3D phosphorylates the N-terminal regulatory domain of t-SNARE syntaxin 4 (but not syntaxin 2 or 3), and this phosphorylation reduces syntaxin 4 binding to SNAP23, suggesting Rab3D controls SNARE complex assembly via calcium-dependent kinase regulation. Co-immunoprecipitation, in vitro kinase assay, EGTA/inhibitor blockade, GST pulldown of syntaxin 4 binding The Journal of biological chemistry Medium 11555639
2001 Rab3D in the AR42J pancreatic tumor cell line undergoes reversible carboxyl-methylation by a geranylgeranyl-specific methyltransferase; inhibitors of geranylgeranylation (lovastatin) or the methyltransferase (N-acetyl-S-geranylgeranyl-L-cysteine but not N-acetyl-S-farnesyl-L-cysteine) shift the rab3D 2D gel isoelectric profile toward the unmethylated (acidic) form. Dexamethasone induction of a regulated secretory pathway increases the unmethylated pool. 2D SDS-PAGE/IEF, pharmacological inhibition, dexamethasone differentiation Biochemical and biophysical research communications Medium 11453651
2002 Dominant-negative Rab3D mutants (N135I and T36N) inhibit CCK-induced amylase release from mouse pancreatic acini by 40–71% without affecting intracellular Ca2+ signaling; wild-type Rab3D localizes to zymogen granules while dominant-negative mutants localize to the basolateral region. The Q81L (GTP-hydrolysis-deficient) mutant has no effect on secretion. Adenoviral transduction of pancreatic acini, amylase secretion assay, CCK dose-response, Ca2+ imaging, immunocytochemistry The Journal of biological chemistry High 11875077
2002 Rab3D-deficient (knockout) mice show enlarged secretory granules in exocrine pancreas and parotid gland (volume ~doubled) without changes in secretion kinetics, enzyme content, or mast cell capacitance; this indicates Rab3D functions during granule maturation (possibly preventing homotypic granule fusion) rather than in the final exocytotic step. Knockout mouse generation, quantitative morphometry, enzyme secretion assays, capacitance patch clamping Molecular and cellular biology High 12192047
2003 Dominant-negative Rab3D (T36N and N135I) reduces GTP-bound endogenous Rab3D by ~70–73% (measured by Rim1 affinity precipitation) without altering total Rab3D, its isoprenylation, membrane association, or targeting to zymogen granules; the mechanism is therefore sequestration of guanine nucleotide exchange factor activity (blocking GDP/GTP exchange on endogenous Rab3D). Rab3D effector (Rim1) affinity precipitation assay, Triton X-114 phase partitioning, cell fractionation, zymogen granule purification, Western blot The Journal of biological chemistry High 14522985
2003 In rat parotid acini, isoproterenol (but not substance P) stimulation induces redistribution of Rab3D from cytosol to the membrane fraction; Rab3D binding to parotid membranes is guanine nucleotide-dependent (wild-type Rab3D but not GTP-hydrolysis-deficient Q81L binds). Both wild-type and Q81L Rab3D inhibit agonist-induced amylase release from permeabilized acini, suggesting an inhibitory/modulatory role in this tissue. Subcellular fractionation, immunoblotting, isoproterenol stimulation in vivo and in vitro, streptolysin-O permeabilization, amylase assay Journal of cellular physiology Medium 14566969
2003 In alveolar epithelial type II cells, Rab3D associates with only ~24% of lamellar bodies (those near the apical membrane); a subset of Rab3D-positive lamellar bodies also acquire filamentous actin coating (2%), and a further subset has actin without Rab3D (9%), consistent with a sequential model where Rab3D release precedes actin decoating during regulated exocytosis. Western blot, immunofluorescence, immunoelectron microscopy, phalloidin labeling American journal of respiratory cell and molecular biology Medium 12933357
2004 Mutant Rab3D proteins (dominant-negative forms) interfere with formation of Weibel-Palade bodies in endothelial cells and consequently reduce histamine-induced acute secretion of vWF, without affecting tPA storage granule formation or exocytosis; siRNA knockdown of annexin A2/S100A10 similarly reduces vWF but not tPA secretion, establishing that distinct mechanisms regulate release of the two products. Dominant-negative Rab3D expression, siRNA knockdown, microinjection of peptide competitors, immunofluorescence, secretion assay The EMBO journal High 15257287
2005 Rab3D is the major Rab3 species in osteoclasts; Rab3D-deficient mice exhibit osteosclerosis with reduced total eroded surface and irregular ruffled borders in osteoclasts. GTP-binding-deficient Rab3D impairs bone resorption in vitro. Wild-type and constitutively active Rab3D associate with a non-endosomal/non-lysosomal subset of post-TGN vesicles, while inactive Rab3D localizes to the TGN and inhibits biogenesis of Rab3D-bearing vesicles, indicating Rab3D modulates a post-TGN trafficking step required for osteoclastic bone resorption. Knockout mouse skeletal analysis, ultrastructural analysis, overexpression of Rab3D mutants, in vitro bone resorption assay, subcellular localization fractionation Molecular and cellular biology High 15923639
2007 In intestinal goblet cells and Brunner's gland acinar cells, Rab3D localizes to cis/medial Golgi compartments (colocalizing with GM-130 and beta-COP markers) rather than secretory granules; stimulation of exocytosis causes partial redistribution of Rab3D from Golgi to cytoplasm and granule field, and rabphilin (a Rab3D effector) shows identical Golgi localization, suggesting Rab3D can regulate the secretory pathway at an earlier (cis-Golgi) stage in these cell types. SDS-PAGE/Western blot, confocal laser scanning microscopy with specific organelle markers, carbamylcholine/deoxycholate stimulation American journal of physiology. Gastrointestinal and liver physiology Medium 17395899
2008 Rab3D directly interacts with the polymeric immunoglobulin receptor (pIgR) in lacrimal gland acinar cells; pull-down assays show both wild-type Rab3D and GDP-locked Rab3DT36N pull down pIgR, but GTP-locked Rab3DQ81L does not; blot overlays with recombinant Rab3DWT confirm direct binding. Secretagogue stimulation reduces pIgR–Rab3D association. Adenoviral overexpression of dominant-negative Rab3DT36N inhibits carbachol-stimulated SC secretion. Immunofluorescence colocalization, pull-down assay with recombinant Rab3D variants, blot overlay, adenoviral overexpression, secretion assay American journal of physiology. Cell physiology High 18171724
2009 The transcription factor MIST1 directly binds conserved CATATG E-boxes in the promoter regions of RAB3D (and RAB26) to activate transcription; RAB3D expression is significantly downregulated in Mist1−/− gastric zymogenic cells. MIST1-expressing cells upregulate RAB3D and form large secretory granules, and this granule formation requires RAB activity (inhibited by RAB prenylation inhibitor or dominant-negative RAB26). ChIP assay (E-box binding), qRT-PCR of Mist1 KO cells, RFP-pepsinogen reporter in MIST1-expressing cancer cells, RAB prenylation inhibitor, dominant-negative transfection Molecular and cellular biology High 20038531
2011 Tctex-1 (a dynein light chain) is a novel Rab3D-interacting partner identified by yeast two-hybrid screen; Tctex-1 binds Rab3D in a GTP-dependent manner and co-occupies Rab3D-bearing vesicles in osteoclasts. Tctex-1 and Rab3D associate with the dynein motor complex and microtubules in osteoclasts. RNAi knockdown of Tctex-1 impairs bone resorption and mislocalizes Rab3D vesicles. Yeast two-hybrid screen, co-immunoprecipitation, vesicle colocalization, dynein complex pulldown, siRNA knockdown, bone resorption assay Molecular and cellular biology High 21262767
2013 Expression of dominant-negative Rab3D N135I in PC12 cells decreases restriction of maturing secretory granules to the F-actin-rich cell cortex, blocks removal of the endoprotease furin from immature secretory granules, and impairs processing of secretogranin II, demonstrating that Rab3D is required for subcellular localization and maturation of immature secretory granules. Dominant-negative Rab3D expression in PC12 cells, immunofluorescence, furin retention assay, secretogranin II processing assay PloS one Medium 23526941
2015 Rab3D promotes cancer cell migration/invasion and activates intracellular AKT/GSK3β signaling to induce EMT; it also regulates extracellular secretion of Hsp90α to promote tumor cell motility. Rab3D knockdown suppresses tumor cell motility in vitro and lung metastasis in vivo. siRNA knockdown, in vitro migration/invasion assays, in vivo orthotopic mouse model, AKT/GSK3β pathway readout, Hsp90α secretion assay Oncotarget Medium 25823663
2016 Calmodulin interacts with Rab3D in a calcium-dependent manner in osteoclasts, as established by yeast two-hybrid screening and confirmed by BRET assay; expression of calcium-insensitive calmodulin (CaM1234) perturbs calmodulin–Rab3D interaction. Calmodulin and Rab3D co-occupy plasma membrane fractions and co-localize at the ruffled border; pharmacological blockade of calmodulin–Rab3D interaction attenuates osteoclastic bone resorption. Yeast two-hybrid, BRET assay, co-sedimentation/fractionation, confocal microscopy, calmidazolium chloride functional assay Scientific reports High 27897225
2016 In lacrimal gland acinar cells from Rab3D-null mice and in a Sjögren's syndrome mouse model, cathepsin S (CTSS) secretion is elevated; CTSS secretion depends on Rab27 (reduced in Rab27-null mice), and high-resolution 3D-SIM reveals Rab3D and Rab27 isoforms occupy microdomains on the same secretory vesicles in different proportions, establishing that the Rab3D/Rab27 balance on individual vesicles tailors their secretory cargo. Rab3D and Rab27 knockout mice, CTSS activity assay in tears, dominant-negative Rab27b, 3D-structured illumination microscopy, in vitro CTSS secretion assay American journal of physiology. Cell physiology High 27076615
2021 Rab3D resides in both trans- and cis-faces of the Golgi in hepatocytes; ethanol treatment causes Rab3D redistribution from trans-Golgi to cis-medial-Golgi. Rab3D is required for COPI vesiculation in the Golgi, and conversely COPI is critical for intra-Golgi distribution of Rab3D. Loss of Rab3D in KO mice causes Golgi enlargement, ER stress, and (with EtOH) apoptosis. ASGP-R bypasses canonical secretory trafficking in Rab3D-null hepatocytes via ER-PM junctions. Rab3D KO mice and cells, EtOH treatment models, COPI vesiculation assay, differential gradient sedimentation, confocal microscopy, ER stress markers, human ALD tissue analysis Hepatology communications High 34494400
2021 RHOF (a Rho GTPase family member) directly interacts with AMPK and increases AMPK phosphorylation, subsequently affecting RAB3D mRNA stability and elevating RAB3D expression; elevated RAB3D amplifies the Warburg effect and promotes HCC cell migration and invasion. Co-IP (RHOF-AMPK interaction), mRNA stability assay, RAB3D knockdown/overexpression, in vitro migration/invasion, metabolic (glycolysis) assays Hepatology Medium 33205519
2022 RAB3D is upregulated by the transcription factor AhR (aryl hydrocarbon receptor) at the transcriptional level; RAB3D promotes PCa cell proliferation, migration, and invasion by activating PI3K/AKT signaling; PI3K inhibitor LY294002 rescues RAB3D overexpression-induced malignant phenotypes. AhR knockdown/overexpression, RAB3D KD/OE, xenograft in vivo model, PI3K inhibitor treatment, Western blot for p-AKT Cell biology international Medium 36153645
2022 RAB3D stabilizes MDM2 protein (knockdown of RAB3D increases MDM2 ubiquitination and degradation); MDM2 activates β-catenin signaling; c-MYC directly binds the RAB3D gene promoter (at -360/-349 and -136/-125 sites) and induces RAB3D transcription, forming a positive feedback loop in AML cells. RAB3D KD/OE in AML cell lines, in vivo xenograft, ubiquitination assay, β-catenin pathway readout, ChIP for c-MYC binding to RAB3D promoter, MDM2 siRNA Cancer gene therapy Medium 36280757
2024 In hepatocytes, RAB3D forms a triple complex with GOLGA4 (golgin A4) and MYH10 (non-muscle myosin IIB) at the trans-Golgi; ethanol-induced RAB3D downregulation causes MYH10 segregation from the Golgi, Golgi fragmentation, tethering of MYH9 (NMIIA) to dispersed Golgi membranes, and extension of the GOLGA4 N-terminal cytoplasmic domain forming GOLGA4-positive phagophores (Golgiphagy). Autophagy inhibition by hydroxychloroquine restores Golgi organization and ASGR distribution. Co-IP, proximity ligation assay, structured illumination microscopy, RAB3D KO and KD models, EtOH treatment, autophagic flux markers (WIPI2, LC3B, SQSTM1), hydroxychloroquine treatment Autophagy High 38591519

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Actin coating of secretory granules during regulated exocytosis correlates with the release of rab3D. Proceedings of the National Academy of Sciences of the United States of America 113 10655489
2002 Rab3D is not required for exocrine exocytosis but for maintenance of normally sized secretory granules. Molecular and cellular biology 110 12192047
2004 Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from endothelial cells. The EMBO journal 109 15257287
2009 RAB26 and RAB3D are direct transcriptional targets of MIST1 that regulate exocrine granule maturation. Molecular and cellular biology 91 20038531
2008 Broadly reactive TaqMan assay for real-time RT-PCR detection of rotavirus in clinical and environmental samples. JIN2@cdc.gov. Journal of virological methods 88 18951923
1996 Rab3D localizes to zymogen granules in rat pancreatic acini and other exocrine glands. The American journal of physiology 87 8843780
1997 Involvement of the ras-like GTPase rab3d in RBL-2H3 mast cell exocytosis following stimulation via high affinity IgE receptors (Fc epsilonRI). Journal of immunology (Baltimore, Md. : 1950) 85 9300704
2005 Rab3D regulates a novel vesicular trafficking pathway that is required for osteoclastic bone resorption. Molecular and cellular biology 79 15923639
2015 High expression of small GTPase Rab3D promotes cancer progression and metastasis. Oncotarget 77 25823663
1997 Overexpression of Rab3D enhances regulated amylase secretion from pancreatic acini of transgenic mice. The Journal of clinical investigation 77 9399951
1996 Rab3D localizes to secretory granules in rat pancreatic acinar cells. European journal of cell biology 77 8738417
2002 A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens. Blood 69 11861285
2000 Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA-5 alloantigens. British journal of haematology 69 10997989
2002 Dominant negative Rab3D inhibits amylase release from mouse pancreatic acini. The Journal of biological chemistry 64 11875077
1995 Nonneuronal expression of Rab3A: induction during adipogenesis and association with different intracellular membranes than Rab3D. Proceedings of the National Academy of Sciences of the United States of America 63 7753798
2018 MicroRNA-506-3p inhibits osteosarcoma cell proliferation and metastasis by suppressing RAB3D expression. Aging 53 29905536
2005 Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes. Transfusion 47 15752154
2015 A Brief Report of the Status of Central Nervous System Metastasis Enrollment Criteria for Advanced Non-Small Cell Lung Cancer Clinical Trials: A Review of the ClinicalTrials.gov Trial Registry. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 46 26725180
1999 Rab3D, a small GTPase, is localized on mast cell secretory granules and translocates to the plasma membrane upon exocytosis. American journal of respiratory cell and molecular biology 46 9870920
2000 Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells. Traffic (Copenhagen, Denmark) 42 11208087
2011 Changes in Rab3D expression and distribution in the acini of Sjögren's syndrome patients are associated with loss of cell polarity and secretory dysfunction. Arthritis and rheumatism 40 21702009
2003 Rapid and reliable genotyping of human platelet antigen (HPA)-1, -2, -3, -4, and -5 a/b and Gov a/b by melting curve analysis. Transfusion 40 12662276
1998 Expression of Rab3D N135I inhibits regulated secretion of ACTH in AtT-20 cells. The Journal of cell biology 40 9442106
2017 ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies. Regenerative medicine 39 28721755
2003 Rab3D and actin reveal distinct lamellar body subpopulations in alveolar epithelial type II cells. American journal of respiratory cell and molecular biology 39 12933357
1999 Expression and localization of Rab3D in rat parotid gland. Biochimica et biophysica acta 37 10395946
2003 Dominant negative Rab3D mutants reduce GTP-bound endogenous Rab3D in pancreatic acini. The Journal of biological chemistry 35 14522985
2018 Evaluating the Completeness of ClinicalTrials.gov. Therapeutic innovation & regulatory science 34 30048602
2001 IgE receptor type I-dependent regulation of a Rab3D-associated kinase: a possible link in the calcium-dependent assembly of SNARE complexes. The Journal of biological chemistry 34 11555639
2020 Lcn2-derived Circular RNA (hsa_circ_0088732) Inhibits Cell Apoptosis and Promotes EMT in Glioma via the miR-661/RAB3D Axis. Frontiers in oncology 33 32154171
2020 CircRNA hsa_circ_0087862 Acts as an Oncogene in Non-Small Cell Lung Cancer by Targeting miR-1253/RAB3D Axis. OncoTargets and therapy 33 32308420
1996 rab3D protein is a specific marker for zymogen granules in gastric chief cells of rats and rabbits. Gastroenterology 33 8608891
2013 Review of ongoing clinical trials in non-small-cell lung cancer: a status report for 2012 from the ClinicalTrials.gov Web site. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 31 23478543
2011 Tctex-1, a novel interaction partner of Rab3D, is required for osteoclastic bone resorption. Molecular and cellular biology 31 21262767
2008 Direct interaction between Rab3D and the polymeric immunoglobulin receptor and trafficking through regulated secretory vesicles in lacrimal gland acinar cells. American journal of physiology. Cell physiology 31 18171724
2021 Ras Homolog Family Member F, Filopodia Associated Promotes Hepatocellular Carcinoma Metastasis by Altering the Metabolic Status of Cancer Cells Through RAB3D. Hepatology (Baltimore, Md.) 30 33205519
2010 Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 30 20592626
2000 Rab3D, a small GTP-binding protein implicated in regulated secretion, is associated with the transcytotic pathway in rat hepatocytes. Hepatology (Baltimore, Md.) 30 10915742
1995 Diffuse vesicular distribution of Rab3D in the polarized neuroendocrine cell line AtT-20. FEBS letters 30 7628619
2023 Usage of Glucagon-Like Peptide-1 for Obesity in Children; Updated Review of Clinicaltrials.gov. Journal of multidisciplinary healthcare 29 37547806
2016 Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome. American journal of physiology. Cell physiology 29 27076615
2021 Chimeric antigen receptor T cell therapy in oncology - Pipeline at a glance: Analysis of the ClinicalTrials.gov database. Critical reviews in oncology/hematology 28 33497760
2017 Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 28472755
2025 CAR-T cell therapy clinical trials: global progress, challenges, and future directions from ClinicalTrials.gov insights. Frontiers in immunology 25 40463393
2020 Characteristics of COVID-19 clinical trials registered with ClinicalTrials.gov: cross-sectional analysis. BMJ open 25 32948577
2017 MiR-27b directly targets Rab3D to inhibit the malignant phenotype in colorectal cancer. Oncotarget 24 29423086
2022 The Current Status of Clinical Trials on Biologics for Cartilage Repair and Osteoarthritis Treatment: An Analysis of ClinicalTrials.gov Data. Cartilage 23 35546280
2021 Inclusion of Patient-Reported Outcomes in Adolescent and Young Adult Phase III Therapeutic Trials: An Analysis of Cancer Clinical Trials Registered on ClinicalTrials.gov. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 23 34838280
2007 Novel localization of Rab3D in rat intestinal goblet cells and Brunner's gland acinar cells suggests a role in early Golgi trafficking. American journal of physiology. Gastrointestinal and liver physiology 23 17395899
2005 Gene frequencies of the HPA-1 to 6 and Gov human platelet antigens in Thai blood donors. Immunohematology 22 15783299
2022 Hsa_circ_0006732 regulates colorectal cancer cell proliferation, invasion and EMT by miR-127-5p/RAB3D axis. Molecular and cellular biochemistry 21 35616807
2015 Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov. Clinical trials (London, England) 21 26085544
2022 Investigational Medicinal Products for the Inner Ear: Review of Clinical Trial Characteristics in ClinicalTrials.gov. Journal of the American Academy of Audiology 20 35609594
2018 The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database. PloS one 20 29718970
2016 Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov. Journal of the American Medical Informatics Association : JAMIA 19 27013523
2023 A target map of clinical combination therapies in oncology: an analysis of clinicaltrials.gov. Discover oncology 18 37603124
2019 The lncRNA HOXA11-AS regulates Rab3D expression by sponging miR-125a-5p promoting metastasis of osteosarcoma. Cancer management and research 18 31191012
2019 Trends in clinical trials for stroke by cell therapy: data mining ClinicalTrials.gov and the ICTRP portal site. NPJ Regenerative medicine 18 31728206
1996 The expression pattern of rab3D in the developing rat exocrine pancreas coincides with the acquisition of regulated exocytosis. European journal of cell biology 18 8905289
2016 Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption. Scientific reports 17 27897225
1996 Expression of Rab3D in dispersed chief cells from guinea pig stomach. Biochimica et biophysica acta 17 8630328
2003 Gene frequencies of the HPA-1 to HPA-13, Oe and Gov platelet antigen alleles in Taiwanese, Indonesian, Filipino and Thai populations. International journal of molecular medicine 16 12964043
2022 CircRNA PRH1-PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR-877-5p. Thoracic cancer 15 35076987
2021 Long non-coding RNA FGD5-AS1 enhances osteosarcoma cell proliferation and migration by targeting miR-506-3p/RAB3D axis. Human cell 15 33891267
2020 Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis. Cell transplantation 15 33054325
2009 Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin II receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel blocker in Japanese elderly high-risk hypertensive patients (ClinicalTrials. gov no. NCT00134160). Hypertension research : official journal of the Japanese Society of Hypertension 15 19444280
2004 Gene frequencies of the HPA-15 (Gov) platelet alloantigen system in Brazilians. Transfusion medicine (Oxford, England) 15 15569238
2003 Rab3D redistribution and function in rat parotid acini. Journal of cellular physiology 15 14566969
2013 Rab3D is critical for secretory granule maturation in PC12 cells. PloS one 14 23526941
2022 Curcumin suppresses lung cancer progression via circRUNX1 mediated miR-760/RAB3D axis. Thoracic cancer 13 36523170
2021 Trends in clinical development of pediatric cancer for PD-1 and PD-L1 inhibitors: an analysis of ClinicalTrials.gov. Journal for immunotherapy of cancer 13 34583971
2021 MicroRNA-125a-5p modulates the proliferation and apoptosis of TM4 Sertoli cells by targeting RAB3D and regulating the PI3K/AKT signaling pathway. Molecular human reproduction 12 34273154
2018 MicroRNA-761 is downregulated in colorectal cancer and regulates tumor progression by targeting Rab3D. Experimental and therapeutic medicine 12 30783458
2001 Carboxyl-methylation of Rab3D in the rat pancreatic acinar tumor cell line AR42J. Biochemical and biophysical research communications 12 11453651
2020 Long Noncoding RNA CAR10 Contributes to Melanoma Progression By Suppressing miR-125b-5p to Induce RAB3D Expression. OncoTargets and therapy 11 32636644
2010 Roles of myosin Va and Rab3D in membrane remodeling of immature secretory granules. Cellular and molecular neurobiology 11 21080055
2004 Phylogenetic analysis of 5'-noncoding regions from the ABA-responsive rab16/17 gene family of sorghum, maize and rice provides insight into the composition, organization and function of cis-regulatory modules. Genetics 11 15579713
1999 Molecular cloning of cDNA encoding human Rab3D whose expression is upregulated with myeloid differentiation. Biochimica et biophysica acta 11 10023084
2022 Hsa_circ_0103232 promotes melanoma cells proliferation and invasion via targeting miR-661/RAB3D. Cell cycle (Georgetown, Tex.) 10 35549813
2022 RAB3D, upregulated by aryl hydrocarbon receptor (AhR), promotes the progression of prostate cancer by activating the PI3K/AKT signaling pathway. Cell biology international 10 36153645
2020 Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov. Drug design, development and therapy 10 32581514
2000 Genomic organization, chromosomal localization, and expression of the murine RAB3D gene. Biochemical and biophysical research communications 10 10891340
1998 Carboxyl methylation of rab3D is developmentally regulated in the rat pancreas: correlation with exocrine function. European journal of cell biology 10 9716267
2021 Long non-coding RNA X-inactive specific transcript promotes osteosarcoma metastasis via modulating microRNA-758/Rab16. Annals of translational medicine 9 34164475
2021 Alcohol-Induced Liver Injury: Down-regulation and Redistribution of Rab3D Results in Atypical Protein Trafficking. Hepatology communications 8 34494400
2012 Effectiveness of cell phones and mypyramidtracker.gov to estimate fruit and vegetable intake. Applied nursing research : ANR 8 23182338
2014 A review of interventional clinical trials in renal cell carcinoma: a status report from the ClinicalTrials.gov WebSite. Clinical genitourinary cancer 7 25450029
1999 Cytosolic RAB3D is associated with RAB escort protein (REP), not RAB-GDP dissociation inhibitor (GDI), in dispersed chief cells from guinea pig stomach. Journal of cellular biochemistry 7 10022613
2024 Alcohol-induced Golgiphagy is triggered by the downregulation of Golgi GTPase RAB3D. Autophagy 6 38591519
2022 Clinical trials of stem cell-based therapies for pediatric diseases: a comprehensive analysis of trials registered on ClinicalTrials.gov and the ICTRP portal site. Stem cell research & therapy 6 35841064
2022 Characteristics of clinical trials for non-small cell lung cancer therapeutic vaccines registered on ClinicalTrials.gov. Frontiers in immunology 6 36341464
2012 Rab3D regulates amylase levels, not agonist-induced amylase release, in AR42J cells. Cellular & molecular biology letters 6 22367855
2026 Glucagon-like peptide 1 receptor agonists in substance use disorders: A systematic review of ClinicalTrials.Gov. Addictive behaviors reports 5 41696398
2024 Advances in Clinical Therapies for Huntington's Disease and the Promise of Multi-Targeted/Functional Drugs Based on Clinicaltrials.gov. Clinical pharmacology and therapeutics 5 38863261
2023 Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov. Radiation oncology (London, England) 5 37016421
2023 Repurposing of H1-receptor antagonists (levo)cetirizine, (des)loratadine, and fexofenadine as a case study for systematic analysis of trials on clinicaltrials.gov using semi-automated processes with custom-coded software. Naunyn-Schmiedeberg's archives of pharmacology 5 37870580
2023 The preventive effects of ondansetron on chemotherapy-induced nausea and vomiting in adult cancer patients: systematic review from ClinicalTrials.gov. Frontiers in pharmacology 5 38074143
2022 RAB3D/MDM2/β-catenin/c-MYC axis exacerbates the malignant behaviors of acute myeloid leukemia cells in vitro and in vivo. Cancer gene therapy 5 36280757
2021 Comprehensive Analysis of Clinical Trials Registration for Lupus Nephritis Therapy on ClinicalTrials.gov. Frontiers in medicine 5 34222288
2024 Variability in Methodology of Erectile Dysfunction Regenerative Therapy Trials on ClinicalTrials.gov. Urology 3 38777189

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