Affinage

RAB12

Ras-related protein Rab-12 · UniProt Q6IQ22

Length
244 aa
Mass
27.2 kDa
Annotated
2026-06-10
30 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB12 is a small GTPase that governs membrane trafficking from recycling endosomes and the trans-Golgi network to lysosomes, controlling the degradation and surface delivery of cargoes including the transferrin receptor, the amino-acid transporter PAT4, and EGFR, and thereby coupling endolysosomal flux to mTORC1 signaling and autophagy (PMID:21718402, PMID:22279614, PMID:24719330, PMID:36739948). Its activation cycle is driven by the GEF DENND3, which is itself autoregulated by an intramolecular interaction between its DENN and actin-binding PHenn domains and acts upstream of RAB12 to promote autophagy and PAT4 trafficking (PMID:24719330, PMID:28249939, PMID:29352104). Active RAB12 engages the RILP family of effectors—RILP, RILPL1, and RILPL2—to direct microtubule- and dynein-dependent retrograde transport, with RILP binding underlying secretory granule transport and negative regulation of mast cell degranulation (PMID:26740112, PMID:33986343). RAB12 is a direct, critical activator of LRRK2 kinase: it binds a distinct site on the LRRK2 Armadillo domain (resolved by cryo-EM), and RAB12 loss markedly reduces LRRK2-mediated phosphorylation of Rab10 and Rab8A in a PPM1H-reversible manner independent of RAB12's own phosphorylation (PMID:37874635, PMID:39343966). RAB12 is recruited to damaged lysosomes where it locally amplifies LRRK2 activity, and pathogenic LRRK2 phosphorylates RAB12 at Ser106, which increases RILPL1 binding and drives perinuclear lysosomal clustering and centrosome/ciliogenesis defects (PMID:37874617, PMID:37086089, PMID:39343966). Phosphorylation thus acts as an effector switch shifting RAB12 preference from RILP toward RILPL1/RILPL2, a switch also executed by LRRK1 in a PKC-dependent manner in mast cells (PMID:41357239). RAB12 additionally functions as a negative regulator of synaptic vesicle exocytosis in vivo and of mitophagy (PMID:42031745, PMID:41959481). Disease-linked variants connect RAB12 to dystonia, while DENND3-driven RAB12 upregulation drives TFR2 degradation and iron overload (PMID:29057844, PMID:36729283).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1996 Medium

    Before any functional assignment, it was unknown whether RAB12 associated with a defined membrane compartment; localizing it to secretory granules established a candidate role in vesicular traffic.

    Evidence GTP-overlay assay and immunogold electron microscopy in atrial cells

    PMID:8575079

    Open questions at the time
    • No functional manipulation
    • Compartment identity in other cell types unresolved
  2. 2011 High

    The cargo and pathway specificity of RAB12 were unknown; identifying it as a regulator of transferrin receptor degradation from recycling endosomes to lysosomes, distinct from EGFR degradation, defined a dedicated trafficking route.

    Evidence siRNA knockdown, constitutively active mutant, lysosomal colocalization, Rab isoform screen

    PMID:21718402 PMID:22279614

    Open questions at the time
    • Effector linking RAB12 to lysosomal delivery not yet identified
    • Mechanism of cargo selection unknown
  3. 2014 High

    How RAB12 is activated and integrated with nutrient signaling was unclear; identifying DENND3 as its GEF placed RAB12 in a pathway controlling PAT4 trafficking, mTORC1 activity, and autophagy.

    Evidence siRNA epistasis, overexpression, mTORC1 and amino-acid readouts in MEFs

    PMID:24719330

    Open questions at the time
    • Direct in vitro GEF kinetics not shown here
    • How DENND3 activity is triggered unresolved
  4. 2014 Medium

    RAB12's role beyond endolysosomal degradation was untested; it was shown to be required for retrograde Shiga toxin transport to the TGN, broadening its trafficking remit.

    Evidence SILAC mass spectrometry, GFP-RAB12 imaging, biochemical toxin transport assay, knockdown

    PMID:24703428

    Open questions at the time
    • Effector mediating TGN-directed transport not identified
    • Single-lab finding
  5. 2016 High

    RAB12 effectors and a physiological context were unknown; identifying RILP as an effector linked RAB12 to dynein-dependent retrograde secretory granule transport and negative control of mast cell degranulation.

    Evidence Pulldown effector identification, live-cell SG imaging, degranulation assay

    PMID:26740112

    Open questions at the time
    • Structural basis of RAB12-RILP binding not yet defined
    • Stimulus-to-activation signaling incomplete
  6. 2017 High

    It was unknown whether RAB12 is a kinase substrate; phosphoproteomics established LRRK2 phosphorylates human RAB12 at Ser106, embedding it in the LRRK2 Rab-substrate network.

    Evidence SILAC phosphoproteomics with two LRRK2 inhibitors, immunoblot validation in HEK293 and PBMCs

    PMID:28860483

    Open questions at the time
    • Functional consequence of Ser106 phosphorylation not yet defined
    • Directionality (RAB12 as activator vs substrate) unresolved
  7. 2017 High

    How DENND3 GEF activity is controlled was unknown; an intramolecular interaction gated by tyrosine 940 was shown to regulate its activity toward RAB12.

    Evidence SEC, FRET, pulldown, in vitro GEF assay, Y940 mutagenesis

    PMID:28249939

    Open questions at the time
    • Upstream signal regulating Y940 unknown
    • Physiological trigger for relief of autoinhibition unclear
  8. 2017 Medium

    Whether RAB12 variants cause disease was untested; rare missense variants in dystonia patients were found to increase GTPase activity and alter lysosomal distribution, linking RAB12 dysfunction to a human phenotype.

    Evidence GTPase activity assay, patient fibroblast localization, serum TfR1 measurement

    PMID:29057844

    Open questions at the time
    • Causality not established by family genetics or rescue
    • Mechanism connecting variant to dystonia unclear
  9. 2018 Medium

    The structural mechanism of DENND3 function was incomplete; a PHenn domain binding actin and the DENN domain was shown to be required for autophagy and thus RAB12 activation.

    Evidence Structural domain analysis, pulldown, mutagenesis, autophagy assay

    PMID:29352104

    Open questions at the time
    • Role of actin binding in nucleotide exchange kinetics unresolved
    • Single-lab structural model
  10. 2021 Medium

    How RAB12 selects among RILP-family effectors was unknown; pulldown and modeling showed RILP, RILPL1, and RILPL2 bind independently, with Lys71 critical for RILPL1/L2 but not RILP, defining the structural basis of effector choice.

    Evidence Pulldown, molecular dynamics modeling, mutagenesis, peptide inhibition

    PMID:33986343

    Open questions at the time
    • Model not validated by experimental structure
    • Determinants of in vivo effector switching not addressed
  11. 2023 High

    Whether RAB12 merely is a LRRK2 substrate or actively regulates LRRK2 was unresolved; an unbiased CRISPR screen established RAB12 as a critical activator binding a novel Armadillo-domain site, distinct from RAB29-mediated activation and independent of RAB12 phosphorylation.

    Evidence Genome-wide CRISPR screen, RAB12 KO in cells and mouse tissues, AlphaFold modeling, PPM1H epistasis

    PMID:37874635

    Open questions at the time
    • Experimental structure of the interaction not yet solved here
    • How RAB12 nucleotide state couples to activation unclear
  12. 2023 High

    The subcellular trigger for RAB12-LRRK2 activation was unknown; RAB12 was shown to be recruited to damaged lysosomes to drive local LRRK2-dependent Rab10 phosphorylation, with PD variants enhancing recruitment.

    Evidence siRNA screen, lysosome immunopurification, imaging, immunoblot

    PMID:37874617

    Open questions at the time
    • Sensor mechanism for lysosomal damage unidentified
    • Link between local activation and downstream pathology incomplete
  13. 2023 High

    The downstream consequence of RAB12 Ser106 phosphorylation was undefined; it was shown to increase RILPL1 binding and drive pathogenic perinuclear lysosomal clustering, connecting phosphorylation to an effector switch and trafficking defect.

    Evidence RAB12 and RILPL1 KO, Ser106 phospho-mutant re-expression, phospho-RAB12 co-IP, confocal imaging

    PMID:37086089

    Open questions at the time
    • Physiological (non-pathogenic) role of the switch unclear
    • Quantitative contribution of RILPL2 not addressed
  14. 2023 Medium

    Whether LRRK2 reads RAB12 nucleotide state was untested; in vitro phosphorylation showed GDP-bound RAB12 is the preferred substrate, indicating conformational recognition.

    Evidence In vitro phosphorylation of GDP- vs GTP-RAB12, circular dichroism, differential scanning fluorimetry

    PMID:37207563

    Open questions at the time
    • In vivo relevance of GDP-state preference unestablished
    • Single in vitro study
  15. 2023 Medium

    RAB12's role in biosynthetic EGFR trafficking was unknown; it was shown to act with the AP-1 adaptor to export newly synthesized EGFR from the TGN, with EGFR Y998 governing AP-1 binding.

    Evidence Gene KO, siRNA, streptavidin pulldown, co-IP, proliferation assays

    PMID:36739948

    Open questions at the time
    • Direct RAB12-AP-1 interaction mechanism unclear
    • Single-lab finding
  16. 2023 Medium

    A disease mechanism via the DENND3/RAB12 axis was untested; a DENND3 activating variant was shown to upregulate RAB12, driving TFR2 lysosomal degradation, hepcidin downregulation, and iron overload.

    Evidence Transfection, lysosomal degradation assay, AAV mouse model, liver iron and hepcidin signaling, patient hepatocytes

    PMID:36729283

    Open questions at the time
    • Direct RAB12-TFR2 trafficking step not structurally defined
    • Generality beyond the DENND3 variant unclear
  17. 2024 High

    The RAB12-LRRK2 interaction lacked an experimental structure and a cellular phenotype; cryo-EM resolved the direct complex and RAB12 was shown to cooperate with LRRK2 to inhibit ciliogenesis and disrupt centrosome homeostasis in astrocytes via Rab10 phosphorylation and RILPL1 recruitment.

    Evidence Cryo-EM, phosphoproteomics, RAB12 KO in astrocytes, cilia/centrosome phenotyping

    PMID:39343966

    Open questions at the time
    • Whether these defects translate to neuronal pathology unaddressed
    • Stoichiometry of the in-cell complex not resolved
  18. 2024 Medium

    Whether RAB12 prenylation contributes to retinal disease was unknown; loss of REP-1 was shown to under-prenylate RAB12, and RAB12 knockdown phenocopied choroideremia RPE dysfunction (reduced autophagic flux, increased mTORC1).

    Evidence CRISPR CHM iPSC-RPE, TMT prenylation proteomics, siRNA, AAV rescue, autophagy/mTORC1 assays

    PMID:38920696

    Open questions at the time
    • Specific contribution of RAB12 among under-prenylated Rabs unclear
    • Mechanistic link from prenylation to autophagy flux incomplete
  19. 2025 Medium

    Whether a kinase other than LRRK2 phosphorylates RAB12 was unknown; LRRK1 was shown to phosphorylate RAB12 in a PKC-dependent manner in activated mast cells, executing the RILP-to-RILPL1/L2 effector switch.

    Evidence Pulldown, LRRK1/LRRK2 siRNA, PKC and LRRK2 inhibitors, mast cell activation assays

    PMID:41357239

    Open questions at the time
    • Phosphosite for LRRK1 not definitively mapped here
    • Single-lab finding
  20. 2026 High

    A neuronal in vivo function was undefined; Rab12 KO mice revealed RAB12 as a negative regulator of synaptic vesicle exocytosis and excitatory striatal transmission, with enrichment in synaptic vesicle fractions.

    Evidence Rab12 KO mouse, striatal electrophysiology, live-cell SV exocytosis imaging, biochemical fractionation, synaptosome proteomics

    PMID:42031745

    Open questions at the time
    • Effector mediating SV exocytosis control unidentified
    • Relationship to LRRK2 activity in neurons unresolved
  21. 2026 Medium

    A role in mitochondrial quality control was untested; a family-wide screen and KO across cell types identified RAB12 as a negative regulator of mitophagy.

    Evidence mt-mKeima/YFP-Parkin siRNA screen, RAB12 KO, mitochondrial content/potential and mtDNA damage assays (preprint)

    PMID:41959481

    Open questions at the time
    • Mechanism linking RAB12 to mitophagy suppression unknown
    • Preprint, awaiting peer review

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying logic connecting RAB12's trafficking roles, its LRRK2-activating function, and its negative regulation of synaptic vesicle exocytosis and mitophagy remains to be integrated into a single mechanistic framework.
  • No common effector tying endolysosomal, synaptic, and mitophagy roles together
  • How nucleotide state, phosphorylation, and effector choice are coordinated in vivo is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005764 lysosome 4 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 2 GO:0005815 microtubule organizing center 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9612973 Autophagy 4 R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 1
Partners
DENND3EGFRLRRK1LRRK2OPTNRILPRILPL1RILPL2

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 RAB12 regulates constitutive degradation of transferrin receptor (TfR) via a pathway from recycling endosomes to lysosomes, independently of the conventional EGFR degradation pathway. Constitutively active RAB12 reduced TfR protein levels; siRNA knockdown of RAB12 or its upstream activator DENND3 increased TfR levels. Knockdown had no effect on EGFR degradation. siRNA knockdown, constitutively active mutant overexpression, colocalization with lysosomes, sequential screening of 60 Rab isoforms Traffic High 21718402 22279614
2014 DENND3 functions as the physiological guanine nucleotide exchange factor (GEF) for RAB12 in mouse embryonic fibroblasts. DENND3 knockdown phenocopied RAB12 knockdown (increased PAT4 levels, increased intracellular amino acids); DENND3 overexpression reduced mTORC1 activity and promoted autophagy in a RAB12-dependent manner, placing DENND3 upstream of RAB12 in controlling PAT4 trafficking from recycling endosomes to lysosomes. siRNA knockdown, overexpression, epistasis (Rab12-dependent rescue), amino acid concentration measurements, mTORC1 activity assay Journal of Biological Chemistry High 24719330
2013 RAB12 physically complexes with the autophagy receptor OPTN, and the M98K-OPTN variant shows enhanced colocalization with RAB12. RAB12 is present in autophagosomes, and knockdown of Rab12 increased TfR levels and reduced M98K-OPTN-induced autolysosomes formation and cell death in retinal ganglion cells (RGC-5). Co-immunoprecipitation, siRNA knockdown, colocalization (fluorescence microscopy), autophagosome formation assay Autophagy Medium 23357852
2016 RAB12 is activated in a stimulus-dependent manner in mast cells and promotes microtubule-dependent retrograde transport of secretory granules (SGs) via interaction with the RILP-dynein complex. RILP was identified as a novel RAB12 effector. RAB12 negatively regulates mast cell degranulation. Pulldown assay (RILP as effector), live-cell imaging of SG transport, knockdown/overexpression with degranulation readout, colocalization Journal of Immunology High 26740112
2017 LRRK2 phosphorylates human RAB12 at Ser106 in a kinase-dependent manner. This was confirmed in HEK293 cells using the selective LRRK2 inhibitor Lu AF58786 in a phosphoproteomic study, and the phosphorylation was reduced by two distinct LRRK2 inhibitors. Phosphoproteomics (SILAC), LRRK2 inhibitor treatment (Lu AF58786 and second inhibitor), immunoblot validation in HEK293 and human PBMCs Scientific Reports High 28860483
2017 DENND3 GEF activity toward RAB12 is regulated through an intramolecular interaction controlled by tyrosine 940, demonstrated by size-exclusion chromatography, FRET, pulldown, and in vitro GEF assays. Size-exclusion chromatography, FRET, pulldown assay, in vitro GEF assay, point mutagenesis (Y940) Journal of Biological Chemistry High 28249939
2014 RAB12 is required for efficient retrograde transport of Shiga toxin from early uptake carriers to the trans-Golgi network. RAB12 localizes to Shiga toxin-induced plasma membrane invaginations (clathrin-independent uptake carriers), and RAB12 depletion reduced toxin reaching TGN membranes and partially protected cells against intoxication. Only TGN46 and CI-M6PR steady-state localization was additionally affected. SILAC/quantitative mass spectrometry, fluorescence microscopy (GFP-RAB12 colocalization), quantitative biochemical toxin transport assay, siRNA knockdown Traffic Medium 24703428
2018 DENND3 contains a PHenn domain with a pleckstrin homology subdomain that binds actin through positively charged residues, and this domain mediates an intramolecular interaction with the DENN domain of DENND3. Both actin binding and DENN domain interaction are required for DENND3 function in autophagy (and thus for RAB12 activation). Structural domain identification, NMR/crystal analysis (structural), pulldown assay, mutational analysis blocking DENN or actin binding, autophagy functional assay Journal of Biological Chemistry Medium 29352104
2021 RAB12 interacts with RILP, RILP-L1, and RILP-L2 independently of each other. Lysine-71 in mouse RAB12 is critical for interaction with RILP-L1 and RILP-L2 but dispensable for RILP binding. A structural model of the RAB12-RILP complex proposes a RILP homodimer interacting with a single active RAB12 molecule via switch I and switch II regions with RILP's RHD domain and C-terminal threonine. Mutational analyses of RILP RHD confirmed its role in secretory granule transport regulation. Pulldown assay, molecular dynamics simulation, mutational analysis, peptide inhibition assay Scientific Reports Medium 33986343
2023 RAB12 is a critical activator of LRRK2 kinase for Rab phosphorylation. Knockout of RAB12 markedly decreased phosphoRab10 levels across multiple cell types and knockout mouse tissues in a LRRK2-dependent and PPM1H-reversible manner. AlphaFold modeling revealed RAB12 binds a novel site in the LRRK2 Armadillo domain; residues at this site influence phosphoRab10 and phosphoRab12 levels distinctly from RAB29-mediated LRRK2 activation. RAB12-driven activation did not require RAB12's own phosphorylation. CRISPR genome-wide screen (flow cytometry for phosphoRab10), RAB12 knockout in multiple cell types and tissues, AlphaFold structural modeling with mutational validation, PPM1H phosphatase epistasis eLife High 37874635
2023 RAB12 is recruited to damaged lysosomes and facilitates local LRRK2-dependent phosphorylation of RAB10 (pT73) at the lysosome. PD-linked LRRK2 variants (R1441G, VPS35 D620N) increased LRRK2 recruitment to lysosomes and elevated lysosomal pT73-Rab10. This defines a conserved mechanism by which RAB12 responds to lysosomal damage to activate LRRK2 locally. siRNA screen, lysosome immunopurification, imaging, immunoblot eLife High 37874617
2023 Pathogenic LRRK2 causes perinuclear lysosomal clustering via RAB12 phosphorylation at Ser106; knockout of RAB12 or its effector RILPL1 abolished clustering. Phosphorylated RAB12 accumulates on clustered lysosomes, and phosphorylation increases RAB12's interaction with RILPL1, thereby disrupting lysosomal transport. RAB12 knockout, RILPL1 knockout, RAB12 re-expression with phospho-site mutants (Ser106), co-immunoprecipitation of phospho-RAB12 with RILPL1, confocal microscopy FASEB Journal High 37086089
2023 LRRK2 phosphorylates RAB12 more efficiently in its GDP-bound form than GTP-bound form in vitro, indicating LRRK2 recognizes the nucleotide-determined structural conformation of RAB12. GDP-bound RAB12 is also more susceptible to heat-induced denaturation, as shown by circular dichroism and differential scanning fluorimetry. In vitro phosphorylation assay (LRRK2 + GDP- vs GTP-bound RAB12), circular dichroism, differential scanning fluorimetry Biochemical and Biophysical Research Communications Medium 37207563
2024 RAB12 forms a direct complex with LRRK2 whose cryo-EM structure was solved. RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes by enhancing RAB10 phosphorylation and recruiting RILPL1. These functions require direct RAB12-LRRK2 interaction and LRRK2 kinase activity. Deletion of RAB12 in astrocytes prevented ciliary and centrosome defects caused by PD-linked LRRK2-G2019S. Cryo-EM structure determination, phosphoproteomics, RAB12 knockout in astrocytes, RILPL1 recruitment assay, primary cilia and centrosome phenotyping Nature Communications High 39343966
2023 RAB12 and the AP-1 clathrin adaptor complex interact with EGFR and regulate export of newly synthesized (wild-type) EGFR from the trans-Golgi network to the cell surface. Tyrosine 998 on EGFR is critical for AP-1 binding and TGN export. The constitutively active EGFR-L858R mutant bypasses this requirement. Gene knockout, siRNA knockdown, streptavidin pulldown, co-immunoprecipitation, cell elongation/proliferation assays Journal of Biological Chemistry Medium 36739948
2017 Rare missense variants of RAB12 found in dystonia patients showed increased GTPase activity and altered subcellular (lysosomal) distribution compared to wild-type in patient-derived fibroblasts and overexpression models. Soluble transferrin receptor 1 levels were reduced in blood of p.Ile196Val carriers. GTPase activity assay, subcellular localization imaging in patient fibroblasts and overexpression models, serum TfR1 measurement Genes Medium 29057844
2023 An activating variant of DENND3 (p.L708V) upregulates RAB12 expression, leading to lysosomal degradation of TFR2 and downregulation of hepcidin via the DENND3/RAB12/TFR2 axis, causing iron overload in a mouse AAV model and in patient hepatocytes. Cell transfection, in vitro lysosomal degradation assay, adeno-associated virus mouse model, liver iron quantification, hepcidin/pSMAD1/5 signaling Hepatology International Medium 36729283
2024 Loss of REP-1 (Rab escort protein 1) in a CHM iPSC-RPE model causes under-prenylation of RAB12. Rab12 knockdown in control RPE cells reduced autophagic flux and increased mTORC1 signaling, phenocopying CHM cells. Gene replacement restored autophagic flux in CHM cells. This identifies RAB12 under-prenylation as a contributor to RPE dysfunction in choroideremia. CRISPR/Cas9 CHM knockout iPSC-RPE, TMT mass spectrometry (prenylation screen), siRNA knockdown, AAV gene replacement, mTORC1 and autophagic flux assays Cells Medium 38920696
2025 In mast cells, LRRK1 (not LRRK2) phosphorylates RAB12 in a PKC-dependent manner upon activation by IgE/antigen or substance P. LRRK1-mediated phosphorylation of RAB12 increases its affinity for RILP-L1 and RILP-L2 while reducing binding to RILP, constituting a phosphorylation-driven effector switch. Pulldown assay, siRNA knockdown of LRRK1 and LRRK2, PKC inhibitor and LRRK2 inhibitor treatment, mast cell activation assays Frontiers in Immunology Medium 41357239
2026 RAB12 is a negative regulator of synaptic vesicle exocytosis and excitatory neurotransmission in vivo. Rab12 KO mice exhibit increased locomotor activity, enhanced presynaptic release probability and excitatory drive onto striatal medium spiny neurons. Live-cell imaging showed Rab12 deletion facilitates and overexpression inhibits synaptic vesicle exocytosis. RAB12 is biochemically enriched in synaptic vesicle-associated fractions. Rab12 KO mouse model, electrophysiology (striatal slices), live-cell imaging of synaptic vesicle exocytosis, biochemical fractionation, synaptosome proteomics NPJ Parkinson's Disease High 42031745
2026 RAB12 is a negative regulator of mitophagy. siRNA and KO of RAB12 augmented clearance of damaged mitochondria basally and after FCCP-induced depolarization across distinct cell types. RAB12 depletion increased mitochondrial content, lowered mitochondrial membrane potential, and reduced mitochondrial DNA damage. Family-wide siRNA screen (mt-mKeima/YFP-Parkin HeLa cells), RAB12 KO across multiple cell types, mitochondrial content and membrane potential assays, mitochondrial DNA damage measurement bioRxivpreprint Medium 41959481
1996 RAB12 protein is associated with atrial secretory granules, demonstrated by GTP-overlay assay and immunogold electron microscopy, suggesting a role in vesicular traffic in these cells. [32P]GTP-overlay assay, immunogold electron microscopy, immunoprecipitation/immunoblot Circulation Research Medium 8575079
2005 RAB12 is associated with small cytoplasmic vesicles (not the Golgi apparatus) in cultured Sertoli cells and NRK cells. When overexpressed, RAB12-associated vesicles accumulate in the perinuclear centrosome region, suggesting a role in vesicular transport from the cell periphery to the perinuclear centrosome region. Immunohistochemistry, immunofluorescence localization in cultured cells, overexpression analysis Molecular Reproduction and Development Low 15791598

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Small GTPase Rab12 regulates constitutive degradation of transferrin receptor. Traffic (Copenhagen, Denmark) 86 21718402
2017 Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells. Scientific reports 80 28860483
2013 M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells. Autophagy 79 23357852
2023 Genome-wide screen reveals Rab12 GTPase as a critical activator of Parkinson's disease-linked LRRK2 kinase. eLife 57 37874635
2016 Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP-Dynein Complex. Journal of immunology (Baltimore, Md. : 1950) 34 26740112
2023 Rab12 is a regulator of LRRK2 and its activation by damaged lysosomes. eLife 33 37874617
2005 Identification of rab12 as a vesicle-associated small GTPase highly expressed in Sertoli cells of rat testis. Molecular reproduction and development 28 15791598
2011 Small GTPase Rab12 regulates transferrin receptor degradation: Implications for a novel membrane trafficking pathway from recycling endosomes to lysosomes. Cellular logistics 26 22279614
1996 Identification of rab12 as a secretory granule-associated small GTP-binding protein in atrial myocytes. Circulation research 22 8575079
2018 A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy. The Journal of biological chemistry 21 29352104
2017 Novel actinomycin group compound from newly isolated Streptomyces sp. RAB12: isolation, characterization, and evaluation of antimicrobial potential. Applied microbiology and biotechnology 20 29270734
2023 Pathogenic LRRK2 compromises the subcellular distribution of lysosomes in a Rab12-RILPL1-dependent manner. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 37086089
2014 Rab12 localizes to Shiga toxin-induced plasma membrane invaginations and controls toxin transport. Traffic (Copenhagen, Denmark) 15 24703428
2024 RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes. Nature communications 14 39343966
2014 Dennd3 functions as a guanine nucleotide exchange factor for small GTPase Rab12 in mouse embryonic fibroblasts. The Journal of biological chemistry 14 24719330
2017 Regulation of DENND3, the exchange factor for the small GTPase Rab12 through an intramolecular interaction. The Journal of biological chemistry 13 28249939
2023 The clathrin adaptor complex-1 and Rab12 regulate post-golgi trafficking of WT epidermal growth factor receptor (EGFR). The Journal of biological chemistry 10 36739948
2021 Rab12 Promotes Radioresistance of HPV-Positive Cervical Cancer Cells by Increasing G2/M Arrest. Frontiers in oncology 9 33718142
2025 In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease. Brain : a journal of neurology 5 39705401
2017 Functional Characterization of Rare RAB12 Variants and Their Role in Musician's and Other Dystonias. Genes 5 29057844
2024 Reduced Retinal Pigment Epithelial Autophagy Due to Loss of Rab12 Prenylation in a Human iPSC-RPE Model of Choroideremia. Cells 4 38920696
2023 DENND3 p.L708V activating variant is involved in the pathogenesis of hereditary hemochromatosis via the RAB12/TFR2 signaling pathway. Hepatology international 4 36729283
2023 LRRK2-mediated phosphorylation and thermal stability of Rab12 are regulated by bound nucleotides. Biochemical and biophysical research communications 4 37207563
2021 Biochemical and structural insights into Rab12 interactions with RILP and its family members. Scientific reports 4 33986343
2026 Rab12 is a regulator of mitophagy and mitochondrial homeostasis. bioRxiv : the preprint server for biology 0 41959481
2026 Disruption of the LRRK2 substrate RAB12 facilitates neurotransmission and causes hyperactivity in mice. NPJ Parkinson's disease 0 42031745
2025 The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis. Life sciences 0 40147529
2025 Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies. bioRxiv : the preprint server for biology 0 40661559
2025 Phosphorylation-driven effector switching of Rab7 and Rab12 by the leucine-rich repeat kinase 1 in mast cells. Frontiers in immunology 0 41357239
2024 RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes. bioRxiv : the preprint server for biology 0 39071328

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