Affinage

RAB30

Ras-related protein Rab-30 · UniProt Q15771

Length
203 aa
Mass
23.1 kDa
Annotated
2026-06-10
26 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB30 is a Golgi/trans-Golgi network (TGN)-resident small GTPase of the Rab family that maintains Golgi structural integrity and governs membrane trafficking between the secretory pathway and the endosomal system (PMID:8863739, PMID:22188167, PMID:33359467). It is continuously recruited to Golgi membranes, and its inactivation disrupts Golgi morphology without blocking bulk anterograde or retrograde flux through the stack (PMID:22188167); consistent with a structural/organizational role, it binds the coiled-coil regions of GRIP-domain golgins (PMID:19001129). At the TGN and recycling endosomes, RAB30 is required for retrograde trafficking of TGN38 from endosomes to the Golgi, and it engages Arf1 and Arf4, whose depletion produces RAB30-decorated tubules from recycling endosomes (PMID:33359467); RAB30 also drives tubular endosome formation and clathrin-independent endocytic cargo trafficking through a BICD2–KIF5B effector axis and is itself a substrate of the GAP TBC1D22B (PMID:41833373). In a GTPase-activity-dependent manner, RAB30 recruits the lipid kinase PI4KB to TGN membranes and to Group A Streptococcus-containing vacuoles, generating PtdIns4P to drive pathogen-induced (but not starvation-induced) autophagosome biogenesis and bacterial degradation (PMID:26771875, PMID:30290718). RAB30 additionally supports selective hepatic sorting of lipoproteins, including ApoA4, to the circulation, and is transcriptionally induced by fasting in a PPARα-dependent manner (PMID:38796472). RAB30 transcription is also a JNK pathway target controlling epithelial morphogenesis in Drosophila (PMID:19427848), and the protein is a substrate for non-canonical phosphoribosyl-ubiquitination by the Legionella effector SdeA (PMID:30850059).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 Medium

    Establishing RAB30 as a distinct Rab-family small GTP-binding protein defined the molecular entity and its broad expression, the necessary starting point for all functional work.

    Evidence cDNA cloning from human melanocytes and chromosome mapping

    PMID:8863739

    Open questions at the time
    • No subcellular localization or function assigned
    • Nucleotide cycling and effectors uncharacterized
  2. 1998 Medium

    Localizing tagged RAB30 to Golgi stacks placed the GTPase at a defined organelle, framing subsequent questions about its trafficking role.

    Evidence Immunoelectron microscopy of transfected COS-1 cells

    PMID:9792283

    Open questions at the time
    • No functional consequence of Golgi residence tested
    • Recruitment mechanism unknown
  3. 2008 Medium

    Identifying golgin coiled-coil regions as RAB30 binding sites provided a candidate set of effectors linking the GTPase to Golgi architecture.

    Evidence In vitro pulldown assays with GRIP-domain golgins and cis-Golgi proteins

    PMID:19001129

    Open questions at the time
    • Binding shown in vitro, not validated in cells
    • Functional role of golgin interaction not tested
  4. 2009 High

    Placing Drosophila Rab30 as a JNK transcriptional target with a dorsal-closure loss-of-function phenotype connected the GTPase to a signaling pathway and a developmental process.

    Evidence Transcriptional reporters, live EGFP-Rab30 imaging, and loss-of-function genetics in Drosophila morphogenesis

    PMID:19427848

    Open questions at the time
    • Molecular effectors driving morphogenetic trafficking unidentified
    • Mammalian relevance of JNK regulation untested
  5. 2011 High

    Showing that RAB30 inactivation disrupts Golgi integrity without impairing transport flux distinguished a structural maintenance role from a cargo-transport role.

    Evidence Time-lapse microscopy, FRAP, dominant-negative/constitutively active mutants, and transport assays in mammalian cells

    PMID:22188167

    Open questions at the time
    • Molecular basis of Golgi maintenance not defined
    • Effectors mediating integrity unknown
  6. 2016 High

    Demonstrating GTPase-dependent recruitment of RAB30 to GAS-containing vacuoles and its requirement for their formation revealed a specific role in pathogen-induced, not starvation, autophagy.

    Evidence siRNA knockdown, GcAV formation and bacterial survival assays, and GTPase-deficient mutants in epithelial cells

    PMID:26771875

    Open questions at the time
    • Effector linking RAB30 to autophagosome membrane unknown at this stage
    • Selectivity for pathogen autophagy mechanistically unexplained
  7. 2018 High

    Identifying PI4KB as a RAB30 effector that generates PtdIns4P at the TGN and GcAVs supplied the lipid-signaling mechanism underlying RAB30-driven pathogen autophagy.

    Evidence Co-IP, siRNA knockdown, PI4KB knockout, PtdIns4P depletion/repletion, and bacterial survival assays

    PMID:30290718

    Open questions at the time
    • Structural basis of RAB30–PI4KB interaction undefined
    • How PtdIns4P drives membrane biogenesis not resolved
  8. 2019 Medium

    Showing RAB30 is a substrate of the Legionella SdeA effector established it as a target of non-canonical phosphoribosyl-ubiquitination during infection.

    Evidence In vitro ubiquitination assay and biochemical characterization of SdeA

    PMID:30850059

    Open questions at the time
    • RAB30 is one of several Rab substrates; specificity unclear
    • Functional consequence of RAB30 modification not tested
  9. 2019 Medium

    Linking Rab30-dependent apical trafficking to Crumbs and PI(4,5)P2 homeostasis embedded the GTPase within a polarity-regulated pathway in epithelia.

    Evidence Genetic knockdown and lipid phosphatase localization in Drosophila salivary glands

    PMID:31697234

    Open questions at the time
    • Direct mechanistic link between Crumbs and Rab30 not defined
    • Rab30-specific contribution to PI(4,5)P2 control unclear
  10. 2021 High

    Mapping RAB30 to the TGN and recycling endosomes, demonstrating its requirement for TGN38 retrograde transport, and identifying Arf1/Arf4 as partners defined its role in endosome-to-Golgi retrograde trafficking.

    Evidence siRNA knockdown, cargo trafficking assays, and GFP-RAB30(Q68L) pulldown-MS in HeLa cells and neurons

    PMID:33359467

    Open questions at the time
    • Whether Arf1/Arf4 are effectors or upstream regulators unresolved
    • Mechanism of tubule formation upon Arf depletion unexplained
  11. 2024 High

    Genetic knockout in mice revealed RAB30 is required for selective sorting of circulating lipoproteins including ApoA4, and is fasting-induced via PPARα, extending its role to physiological hepatic secretion.

    Evidence Conditional/whole-body knockout mice, super-resolution imaging, in vivo BioID, and serum ApoA4/lipid measurements

    PMID:38796472

    Open questions at the time
    • Molecular sorting machinery distinguishing secreted vs retained lipoproteins unknown
    • Effectors mediating selective sorting unidentified
  12. 2026 Medium

    Identifying RAB30 as required for tubular endosome formation and CIE cargo trafficking, regulated by GAP TBC1D22B and acting through a BICD2–KIF5B axis, expanded its trafficking role to motor-driven endosomal tubulation.

    Evidence siRNA knockdown screening, dominant-negative expression, and CIE cargo trafficking assays in HeLa cells

    PMID:41833373

    Open questions at the time
    • No in vitro reconstitution of the RAB30–BICD2–KIF5B axis
    • Direct binding of RAB30 to BICD2/KIF5B not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RAB30 mechanistically coordinates its multiple roles — Golgi maintenance, retrograde and tubular trafficking, lipoprotein sorting, and pathogen autophagy — and which GEFs and effectors switch it between these functions.
  • No GEF identified for RAB30 activation
  • No structural model of RAB30–effector complexes
  • Integration of context-specific effector usage unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3
Localization
GO:0005768 endosome 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
ARF1ARF4BICD2KIF5BPI4KBTBC1D22B

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RAB30 encodes a novel 203 amino acid small GTP-binding protein of the Rab family, cloned from human melanocytes, mapping to chromosome 11, with nearly ubiquitous tissue expression. Molecular cloning from cDNA library, chromosome mapping Gene Medium 8863739
1998 Epitope-tagged RAB30 expressed in COS-1 cells localizes to Golgi stacks, as determined by immunoelectron microscopy. Immunoelectron microscopy of transfected COS-1 cells British journal of haematology Medium 9792283
2008 GRIP domain golgins (coiled-coil Golgi proteins) contain binding sites for RAB30 within their coiled-coil regions (distinct from their Golgi-targeting C termini), as demonstrated by binding assays using Drosophila GRIP domain golgins and their cis-Golgi counterparts GM130 and GMAP-210 orthologs. In vitro binding assays (pulldown) with Rab family G proteins and Golgi coiled-coil proteins The Journal of cell biology Medium 19001129
2009 Drosophila Rab30 is a transcriptional target of the JNK signaling pathway; EGFP-Rab30 localizes to the trans-Golgi and small unidentified vesicles, and moves in a microtubule-dependent, polarized dorso-ventral manner in leading-edge cells during dorsal closure. Loss-of-function of Rab30 impairs JNK-dependent dorsal closure, head involution, and thorax closure. Transcriptional reporter assays, live imaging of EGFP-Rab30, loss-of-function genetic analysis in Drosophila morphogenesis Developmental biology High 19427848
2011 Mammalian RAB30 localizes predominantly to the Golgi apparatus and is continuously recruited to it (demonstrated by time-lapse microscopy and FRAP). Inactivation of RAB30 disrupts Golgi morphological integrity but does not impair anterograde or retrograde transport through the Golgi. Time-lapse microscopy, FRAP, dominant-negative/constitutively active Rab30 expression, transport assays Biology of the cell High 22188167
2016 RAB30, a Golgi-resident Rab GTPase, is recruited to GAS-containing autophagosome-like vacuoles (GcAVs) in response to Group A Streptococcus infection in epithelial cells, in a GTPase activity-dependent manner. Knockdown of RAB30 significantly reduces GcAV formation efficiency and impairs intracellular GAS degradation. RAB30 is not required for starvation-induced autophagosome formation, indicating a specific role in pathogen-induced autophagy. siRNA knockdown, fluorescence microscopy, GcAV formation assay, bacterial survival assay, dominant-negative/GTPase-deficient mutants PloS one High 26771875
2018 RAB30 recruits PI4KB (phosphatidylinositol 4-kinase beta) to the Golgi apparatus and to GcAVs; TGN vesicles are incorporated into GcAVs via RAB30. Depletion of RAB30 decreases PI4KB localization to the TGN and GcAVs. PtdIns4P (produced by PI4KB) is required for GcAV formation. PI4KB knockout suppresses GcAV-mediated autophagy and increases GAS survival. Co-immunoprecipitation, siRNA knockdown, PI4KB knockout, pharmacological depletion/repletion of PtdIns4P, fluorescence microscopy, bacterial survival assay Autophagy High 30290718
2019 In Drosophila salivary glands, the polarity protein Crumbs maintains Rab30-dependent apical trafficking; Crumbs knockdown disrupts Rab30-dependent trafficking, and this is linked to dysregulation of apical PI(4,5)P2 homeostasis. Genetic knockdown in Drosophila, fluorescence imaging, lipid phosphatase localization eLife Medium 31697234
2019 RAB30 is phosphoribosyl-ubiquitinated by the Legionella pneumophila effector SdeA (SidE family), a novel ubiquitination mechanism independent of classical E1/E2 machinery and ATP. In vitro ubiquitination assay, biochemical characterization of SdeA activity Methods in enzymology Medium 30850059
2021 RAB30 localizes primarily to the TGN and recycling endosomes (and minor levels in Golgi stack and early endosomes) in HeLa cells and primary neurons. Silencing RAB30 causes dispersal of early and recycling endosomes and TGN compartments. RAB30 is required for retrograde trafficking of TGN38 from endosomes to the Golgi, but not for endocytic recycling of transferrin receptor. Pull-down/MS of the constitutively active RAB30(Q68L) mutant identified Arf1 and Arf4 as interaction partners; knockdown of Arf1 and Arf4 results in GFP-RAB30-decorated tubules from recycling endosomes. siRNA knockdown, fluorescence microscopy, cargo trafficking assay (TGN38, transferrin receptor), GFP pulldown + mass spectrometry, Arf1/4 knockdown Experimental cell research High 33359467
2024 RAB30 is induced in mouse liver by fasting in a PPARα-dependent manner. Live-cell super-resolution imaging and in vivo proximity labeling show RAB30-marked vesicles are highly dynamic and interact with proteins throughout the secretory pathway. Liver-specific or whole-body Rab30 knockout mice with concomitant Cpt2 liver-specific deletion show suppression of serum dyslipidemia (decreased circulating but not hepatic ApoA4 protein), indicating RAB30 is required for selective sorting of lipoproteins (including ApoA4) to the circulation, particularly under lipid burden. Conditional/whole-body knockout mice, live-cell super-resolution imaging, in vivo proximity labeling (BioID), serum lipid/ApoA4 measurements Nature communications High 38796472
2026 RAB30, a Golgi-resident Rab GTPase, is a novel regulator of tubular endosome formation in HeLa cells. RAB30 is a target of the GAP TBC1D22B (knockdown of TBC1D22B causes loss of tubular structures). Knockdown screening identified RAB30 as required for tubular endosome formation and CIE (clathrin-independent endocytosis) cargo trafficking to the plasma membrane. A RAB30–BICD2–KIF5B axis is implicated in tubular endosome formation. Comprehensive siRNA knockdown screening, dominant-negative Rab expression, fluorescence microscopy of tubular endosomes, CIE cargo trafficking assay Cell structure and function Medium 41833373

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins. The Journal of cell biology 157 19001129
2021 A molecular signature associated with prolonged survival in glioblastoma patients treated with regorafenib. Neuro-oncology 66 32661549
2013 MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects. Gene 55 24080485
2017 Insights into the role of hepatocyte PPARα activity in response to fasting. Molecular and cellular endocrinology 52 28774777
2011 Release of TNF-α from macrophages is mediated by small GTPase Rab37. European journal of immunology 46 21805469
2011 Rab30 is required for the morphological integrity of the Golgi apparatus. Biology of the cell 43 22188167
2021 LPI-deepGBDT: a multiple-layer deep framework based on gradient boosting decision trees for lncRNA-protein interaction identification. BMC bioinformatics 39 34607567
1996 Molecular cloning of two novel rab genes from human melanocytes. Gene 39 8863739
2010 Oral benzo[a]pyrene-induced cancer: two distinct types in different target organs depend on the mouse Cyp1 genotype. International journal of cancer 36 20127859
2016 Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes. PloS one 35 26771875
2009 JNK signalling influences intracellular trafficking during Drosophila morphogenesis through regulation of the novel target gene Rab30. Developmental biology 30 19427848
1998 Small GTP-binding proteins in human endothelial cells. British journal of haematology 25 9792283
2018 RAB30 regulates PI4KB (phosphatidylinositol 4-kinase beta)-dependent autophagy against group A Streptococcus. Autophagy 17 30290718
2019 Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2 in Drosophila. eLife 15 31697234
2021 A role for Rab30 in retrograde trafficking and maintenance of endosome-TGN organization. Experimental cell research 14 33359467
2022 Integrating intracellular nanovesicles into integrin trafficking pathways and beyond. Cellular and molecular life sciences : CMLS 10 35657500
2022 Swelling-induced upregulation of miR-141-3p inhibits hepatocyte proliferation. JHEP reports : innovation in hepatology 9 35287291
2011 Elevation and characteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse. International journal of molecular medicine 9 21308349
2024 Rab30 facilitates lipid homeostasis during fasting. Nature communications 8 38796472
2022 The complex, dynamic SpliceOme of the small GTPase transcripts altered by technique, sex, genetics, tissue specificity, and RNA base editing. Frontiers in cell and developmental biology 7 36467401
2019 Purification and functional characterization of the DUB domain of SdeA. Methods in enzymology 7 30850059
2024 Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer. Clinical proteomics 5 39385083
2025 A novel lncRNA-mediated signaling axis governs cancer stemness and splicing reprogramming in hepatocellular carcinoma with therapeutic potential. Journal of experimental & clinical cancer research : CR 2 41068948
2024 Identification of differentially expressed genes and polymorphisms related to intramuscular oleic-to-stearic fatty acid ratio in pigs. Animal genetics 1 39593270
2022 Clinical significance of germline telomere length and associated genetic factors in patients with neuroblastoma. Scientific reports 1 35902621
2026 Identification of Rab30 as a novel regulator of tubular endosomes. Cell structure and function 0 41833373

Missed literature

Know a paper Affinage missed for RAB30? Flag it for the maintainers and the community.

No submissions yet.