Affinage

RAB22A

Ras-related protein Rab-22A · UniProt Q9UL26

Length
194 aa
Mass
21.9 kDa
Annotated
2026-06-10
65 papers in source corpus 24 papers cited in narrative 24 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

RAB22A is an endosomal small GTPase that governs cargo sorting and tubular recycling in the clathrin-independent endocytosis pathway, cycling between GTP- and GDP-bound states to control distinct trafficking steps (PMID:11739636, PMID:15181155). Active RAB22A is required to generate tubular recycling intermediates carrying clathrin-independent cargo such as MHC class I and the transferrin receptor, and its subsequent inactivation is required for fusion of these tubules with the plasma membrane, placing it upstream of and distinct from RAB11A in the recycling itinerary (PMID:15181155, PMID:16537905). It builds the recycling endosome machinery by organizing a BLOC-1–BLOC-2–KIF13A complex on endosomes and directly binding the kinesin-3 motor KIF13A to relieve its autoinhibition and promote motor dimerization for endosome tubulation (PMID:30404817, PMID:33536208); its specific GEF Vps9d1 activates RAB22A to drive this tubular endosome formation (PMID:36762583). Through these activities RAB22A controls the recycling versus degradation fate of multiple surface cargoes, including CD147 and EGFR, the latter by recruiting the RAB7A GAP TBC1D2B to block lysosomal delivery while engaging the RAB11A GEF SH3BP5L to promote surface recycling and microvesicle packaging, a process tuned by EGFR phosphorylation of RAB22A at Tyr136 (PMID:28433697, PMID:39051763). RAB22A also drives extracellular vesicle and microvesicle shedding, induced under hypoxia downstream of HIF, and supports breast cancer metastasis (PMID:24938788). Beyond recycling, RAB22A nucleates a non-canonical secretory autophagy pathway: it engages PI4K2A to generate PI4P that recruits the ATG12–ATG5–ATG16L1 complex, building ER-derived non-canonical autophagosomes that fuse with RAB22A-positive endosomes to form the Rafeesome, while RAB22A-mediated RAB7 inactivation prevents lysosomal fusion and enables secretion of activated STING-containing vesicles for antitumor immunity (PMID:36280710, PMID:40301304). In osteosarcoma, chromosomal translocation–derived Rab22a-NeoF1 fusion proteins use the RAB22A 1–38 moiety to bind SmgGDS-607 and release GTP-bound RhoA, activating RhoA to drive lung metastasis; this fusion is controlled by p300/CBP acetylation at K7 and by PINK1/STUB1-directed lysosomal degradation (PMID:32483387, PMID:32685017, PMID:36529692).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2001 High

    Established RAB22A as an endosome-associated GTPase whose nucleotide state controls endocytic function, answering where the protein acts and that its activity cycle matters.

    Evidence GFP-tagged constructs, Q64L/S19N mutagenesis and fluid-phase endocytosis assays in CHO cells

    PMID:11739636

    Open questions at the time
    • No effectors or GEF/GAP identified
    • Mechanism linking GTPase state to endosome enlargement unresolved
  2. 2004 High

    Defined RAB22A's specific role in clathrin-independent recycling, showing activation drives tubule formation while inactivation is needed for surface fusion, and that it acts at a step distinct from RAB11A.

    Evidence Dominant-negative/constitutively active mutants, siRNA, MHCI recycling and epistasis analysis

    PMID:15181155

    Open questions at the time
    • Tubulation machinery downstream of RAB22A not identified
    • Mechanism coupling inactivation to fusion unknown
  3. 2005 Medium

    Extended RAB22A function to endosome-to-TGN retrograde transport, distinguishing it from endosome-to-lysosome routes.

    Evidence Mutant expression, cholera toxin retrograde and CI-M6PR localization assays in CHO cells

    PMID:15748882

    Open questions at the time
    • Single-lab overexpression readout
    • No retrograde effectors defined
  4. 2006 High

    Showed RAB22A sorts transferrin receptor from sorting to recycling endosomes and organizes the perinuclear recycling center, broadening it beyond clathrin-independent cargo.

    Evidence Wild-type/Q64L expression, siRNA, kinetic transferrin recycling in CHO and HeLa cells

    PMID:16537905

    Open questions at the time
    • Molecular sorting machinery not identified
  5. 2014 High

    Connected RAB22A to hypoxia-driven microvesicle shedding and metastasis, linking endosomal recycling to extracellular vesicle biology in cancer.

    Evidence HIF manipulation, RAB22A siRNA, microvesicle quantification, orthotopic breast cancer xenograft

    PMID:24938788

    Open questions at the time
    • Molecular mechanism of vesicle budding by RAB22A not resolved at this stage
    • Cargo content of microvesicles undefined
  6. 2016 High

    Demonstrated RAB22A is required for MHC-I recycling and antigen cross-presentation in dendritic cells, giving the recycling pathway an immunological output.

    Evidence siRNA knockdown, MHC-I trafficking and multiple cross-presentation assays in DCs

    PMID:27861124

    Open questions at the time
    • Effectors mediating MHC-I recycling in DCs not defined
  7. 2017 Medium

    Identified CD147 as a RAB22A-dependent recycling cargo, tying RAB22A recycling activity to tumor cell migration.

    Evidence Co-IP, siRNA, CD147 recycling and migration/invasion assays

    PMID:28433697

    Open questions at the time
    • Single-lab study
    • Direct binding interface unmapped
  8. 2018 High

    Resolved the recycling endosome machinery by placing RAB22A upstream of the BLOC-1–BLOC-2–KIF13A complex as its membrane organizer.

    Evidence RNAi screen, Co-IP, live-cell RE dynamics and cargo recycling in melanocytes

    PMID:30404817

    Open questions at the time
    • How RAB22A recruits the complex mechanistically not fully defined at this stage
  9. 2018 Medium

    Linked RAB22A to ER-derived protein delivery at endosomes and antigen translocation to the cytosol in dendritic cells.

    Evidence siRNA in DCs, ER marker immunofluorescence, cytosol translocation assay

    PMID:28960134

    Open questions at the time
    • Single-lab functional study
    • Molecular basis of ER-endosome contribution unclear
  10. 2020 High

    Discovered the oncogenic Rab22a-NeoF1 fusion mechanism, showing the RAB22A 1–38 moiety binds SmgGDS-607 to release active RhoA and drive osteosarcoma lung metastasis.

    Evidence Fusion gene sequencing, Co-IP, RhoA-GTP assay, peptide disruption in orthotopic model

    PMID:32483387

    Open questions at the time
    • Relationship of fusion to wild-type RAB22A function not addressed
  11. 2020 High

    Identified K7 acetylation by p300/CBP as a switch controlling Rab22a-NeoF1 binding to SmgGDS-607 and its pro-metastatic activity.

    Evidence MS K7ac identification, K7R mutagenesis, Co-IP, RhoA assay, migration and orthotopic metastasis model

    PMID:32685017

    Open questions at the time
    • Whether wild-type RAB22A is similarly regulated unknown
  12. 2020 Medium

    Placed RAB22A downstream of RAB14 in epithelial polarity through an EFA6–Arf6 axis.

    Evidence siRNA, 3D MDCK lumen assay, Co-IP with EFA6, Arf6 activity assay, epistasis rescue

    PMID:32281471

    Open questions at the time
    • Single-lab study
    • Direct vs indirect EFA6 interaction not fully resolved
  13. 2021 High

    Provided the molecular mechanism of motor activation, showing RAB22A binds KIF13A NC-CC1 domains to relieve autoinhibition and promote dimerization for endosome tubulation.

    Evidence Single-molecule fluorescence and in vitro motility assays, domain mutagenesis, Co-IP

    PMID:33536208

    Open questions at the time
    • Structural basis of the RAB22A-KIF13A interface not solved
  14. 2021 High

    Showed how Rab22a-NeoF1 is exported and spreads metastatic signaling via HSP90/KFERQ-mediated exosomal sorting with PYK2.

    Evidence Co-IP, exosome isolation, KFERQ motif mutagenesis, RhoA/STAT3 assays, lung metastasis model

    PMID:33568623

    Open questions at the time
    • Whether wild-type RAB22A uses the same export route unknown
  15. 2022 High

    Established RAB22A as the nucleator of a non-canonical secretory autophagy pathway (Rafeesome) that secretes activated STING via PI4K2A-PI4P-ATG engagement and RAB7 inactivation.

    Evidence Co-IP, PI4P lipid assay, organelle colocalization, RAB7 activity assay, EM, IFNβ secretion and tumor model

    PMID:36280710

    Open questions at the time
    • How RAB22A selects ER membrane for autophagosome formation not yet defined here
  16. 2022 High

    Defined the STUB1/NDP52/PINK1-driven lysosomal degradation pathway controlling Rab22a-NeoF1 levels and identified it as a druggable node.

    Evidence E3 screening, ubiquitination assay, K112R/S120A mutagenesis, PINK1 kinase assay, metastasis model

    PMID:36529692

    Open questions at the time
    • Whether wild-type RAB22A is regulated by the same axis unknown
  17. 2022 Medium

    Linked RAB22A to PI3K/Akt/mTOR signaling via direct interaction with PI3K p85α in lung adenocarcinoma.

    Evidence Co-IP, siRNA/overexpression, phospho-Western blots, proliferation/migration assays, rapamycin rescue

    PMID:35487271

    Open questions at the time
    • Single-lab study
    • Direct binding interface not mapped
  18. 2022 Medium

    Showed RAB22A cooperates with RAB5 and viral NS4B to facilitate classical swine fever virus entry through early endosomes.

    Evidence GST pull-down, Co-IP with nucleotide-state mutants, confocal colocalization, viral replication assay

    PMID:35134740

    Open questions at the time
    • Single-lab study
    • Relevance to human pathogens not addressed
  19. 2023 High

    Identified Vps9d1 as the specific GEF that activates RAB22A to drive tubular endosome formation, defining the upstream activation input.

    Evidence siRNA, GEF activity assay, constitutively active RAB22A rescue, RAB5A controls, CIE cargo assays

    PMID:36762583

    Open questions at the time
    • Spatial/temporal regulation of Vps9d1 recruitment unresolved
  20. 2024 High

    Dissected how RAB22A coordinates RAB7A inactivation (via TBC1D2B) and RAB11A activation (via SH3BP5L) to recycle EGFR into microvesicles, with EGFR feedback phosphorylating RAB22A at Tyr136.

    Evidence RAB RNAi screen, Co-IP of effectors, RAB7A/RAB11A activity assays, EGFR phospho-assay, MV isolation

    PMID:39051763

    Open questions at the time
    • Structural basis of effector switching unknown
  21. 2024 Medium

    Identified TBC1D31 as a RAB22A GAP that limits RAB22A-mediated EGFR endolysosomal degradation and thereby sustains EGFR signaling in HCC.

    Evidence GAP activity assay, EGFR trafficking assay, Co-IP, HCC in vitro/in vivo models

    PMID:39206796

    Open questions at the time
    • Single-lab study
    • Regulation of TBC1D31 recruitment unknown
  22. 2024 Low

    Reported an endogenous HIF-1α–RAB22A complex under hypoxia, but only in endogenous context.

    Evidence Co-IP of endogenous proteins and molecular docking; overexpression showed no interaction

    PMID:38647725

    Open questions at the time
    • Single Co-IP, not reciprocally validated
    • Negative overexpression result limits interpretation
    • Functional consequence undefined
  23. 2025 Medium

    Defined a RAB22A–PKM2–pSNAP-23 cascade that boosts exosome secretion and transmits chemoresistance in colorectal cancer.

    Evidence Co-IP, ubiquitination and SNAP-23 phospho-assays, exosome isolation, conditioned medium transfer

    PMID:40957949

    Open questions at the time
    • Single-lab study
    • Direct vs indirect PKM2 interaction unclear
  24. 2025 High

    Resolved the ER membrane source of Rafeesome vesicles, showing RAB22A/TMEM33/RTN4 assembly drives RTN4 oligomerization and curvature for ATG9A-mediated non-canonical autophagosome formation.

    Evidence Co-IP of multi-protein assembly, RTN4 TM2 mutagenesis, oligomerization assay, EM, secretion assay

    PMID:40301304

    Open questions at the time
    • How RAB22A nucleotide state regulates the assembly not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RAB22A's GTPase cycle is spatially coordinated to switch between its recycling, retrograde, secretory-autophagy, and vesicle-shedding roles, and whether the diverse cancer-associated signaling interactions reflect a single unifying biochemical mechanism.
  • No structural model of RAB22A bound to its competing effectors
  • Determinants selecting recycling vs secretory-autophagy fate unknown
  • Relationship between wild-type RAB22A regulation and Rab22a-NeoF1 fusion regulation unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 5 GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-9609507 Protein localization 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
EFA6KIF13API4K2ASH3BP5LTBC1D2BTBC1D31TMEM33VPS9D1
Complex memberships
BLOC-1–BLOC-2–KIF13A complexRAB22A/TMEM33/RTN4 assemblyRafeesome

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Rab22a associates with early and late endosomes but not lysosomes in CHO cells. Overexpression causes enlargement of early and late endosomes. A constitutively active mutant (Q64L) also associates with lysosomes and autophagosomes. Wild-type and dominant-negative (S19N) forms decrease fluid-phase endocytosis, while Q64L does not inhibit bulk endocytosis. GFP-tagged protein expression, site-directed mutagenesis, fluorescence microscopy with endosomal markers, fluid-phase endocytosis assay Journal of cell science High 11739636
2004 Rab22a is associated with tubular recycling intermediates containing clathrin-independent cargo (MHC class I). Dominant-negative Rab22a or siRNA-mediated depletion inhibits both tubule formation and MHCI recycling. Constitutively active Rab22a promotes tubule formation but still blocks final recycling fusion, indicating Rab22a activation is required for tubule formation and inactivation is required for membrane fusion with the surface. Rab11a dominant-negative inhibits MHCI recycling without affecting tubule formation, placing Rab22a and Rab11a at distinct steps. Dominant-negative and constitutively active mutant expression, siRNA knockdown, fluorescence microscopy, recycling assays Molecular biology of the cell High 15181155
2004 Overexpression of wild-type Rab22a or its GTP-hydrolysis-deficient mutant Q64L delays retrograde transport of cholera toxin from endosomes to the Golgi apparatus and accumulates the cation-independent mannose-6-phosphate receptor in endosomes, implicating Rab22a in endosome-to-TGN trafficking. No effect on endosome-to-lysosome transport was detected. Mutant expression, cholera toxin retrograde trafficking assay, CI-M6PR localization, fluorescence microscopy in CHO cells Experimental cell research Medium 15748882
2006 Rab22a controls the sorting of transferrin receptor from sorting endosomes to recycling endosomes. Expression of wild-type or Q64L canine Rab22a redistributes transferrin receptor to large Rab22a-positive peripheral structures and strongly inhibits recycling from those compartments. siRNA depletion of Rab22a disorganizes the perinuclear recycling center and strongly inhibits transferrin recycling, without affecting early internalization. Wild-type and mutant Rab22a expression, siRNA knockdown, kinetic transferrin recycling assays, fluorescence microscopy in CHO and HeLa cells Molecular and cellular biology High 16537905
2014 Under hypoxia, HIF-dependent transcriptional induction of RAB22A mediates microvesicle shedding from breast cancer cells. RAB22A colocalizes with budding microvesicles at the cell surface. Knockdown of RAB22A impairs breast cancer metastasis in an orthotopic mouse model. HIF knockdown/overexpression, RAB22A siRNA, microvesicle quantification, colocalization by fluorescence microscopy, orthotopic xenograft metastasis model Proceedings of the National Academy of Sciences of the United States of America High 24938788
2016 Rab22a is recruited to dendritic cell endosomes and phagosomes (including Toxoplasma gondii-containing vacuoles) and is required for MHC-I intracellular recycling and antigen cross-presentation. Rab22a silencing drastically reduces the intracellular pool and recycling of MHC-I and hampers cross-presentation of soluble, particulate, and T. gondii-associated antigens, without affecting classical MHC-I presentation through the secretory pathway. Rab22a siRNA knockdown in dendritic cells, MHC-I trafficking assays, cross-presentation assays, fluorescence microscopy EMBO reports High 27861124
2017 Rab22a interacts with CD147 (a cargo protein entering cells via clathrin-independent endocytosis) and is required for its recycling back to the plasma membrane. Knockdown of Rab22a blocks CD147 recycling, promotes CD147 degradation, and suppresses lung cancer cell migration and invasion. Co-immunoprecipitation, Rab22a siRNA knockdown, CD147 recycling assay, migration and invasion assays Experimental cell research Medium 28433697
2018 Rab22A forms a complex with BLOC-1, BLOC-2, and the kinesin-3 motor KIF13A on endosomes. Rab22A depletion reduces RE dynamics, causes cargo accumulation in early/sorting endosomes or lysosomes, and reduces membrane association of BLOC-1/BLOC-2. These defects phenocopy BLOC-1/BLOC-2-deficient cells, placing Rab22A upstream as an organizer of the BLOC-1–BLOC-2–KIF13A complex for recycling endosome biogenesis. RNAi screen, Co-immunoprecipitation, Rab22A siRNA knockdown, live-cell imaging of recycling endosome dynamics, cargo recycling assays in melanocytes EMBO reports High 30404817
2018 Rab22a depletion in dendritic cells does not prevent ER-derived protein delivery to phagosomes but reduces ER-derived proteins at endosomes (labeled by fluid-phase marker) and impairs soluble antigen translocation to the cytosol. Rab22a deficiency also alters early endosomal maturation. Rab22a siRNA knockdown in DCs, immunofluorescence for ER markers in endosomes/phagosomes, cytosol translocation assay Small GTPases Medium 28960134
2020 Osteosarcoma chromosomal translocations produce Rab22a-NeoF fusion proteins in which the Rab22a1-38 moiety binds SmgGDS-607 (a GTP-GDP exchange factor for RhoA), facilitating release of GTP-bound RhoA from SmgGDS-607, thereby increasing RhoA activity and driving lung metastasis. Disrupting the Rab22a-NeoF1–SmgGDS-607 interaction with a synthetic peptide prevents lung metastasis in an orthotopic model. Identification of fusion genes by sequencing, Co-immunoprecipitation, RhoA activation assay, orthotopic osteosarcoma metastasis model, peptide disruption experiment Nature cell biology High 32483387
2020 Rab22a-NeoF1 K7 is acetylated by p300/CBP and deacetylated by HDAC6 and SIRT1. A K7R acetylation-deficient mutant fails to bind SmgGDS-607 and loses the ability to activate RhoA, promote cell migration/invasion, and induce lung metastasis in vivo. p300/CBP inhibitor C646 also abolishes these functions. Mass spectrometry identification of K7ac, Co-IP, RhoA activation assay, Transwell migration/invasion, orthotopic osteosarcoma mouse model, site-directed mutagenesis (K7R) Theranostics High 32685017
2020 Rab22a acts downstream of Rab14 to establish epithelial polarity. Rab22a co-immunoprecipitates with the Arf6 GEF EFA6, and Rab22a knockdown causes decreased active Arf6 and retention of EFA6 in intracellular puncta, leading to multi-lumen phenotype. Overexpression of Rab22a rescues the Rab14 knockdown multi-lumen phenotype, placing Rab22a downstream of Rab14 in the polarity pathway. Rab22a siRNA knockdown, 3D MDCK culture lumen assay, co-immunoprecipitation with EFA6, Arf6 activity assay, epistasis rescue experiment Small GTPases Medium 32281471
2021 Rab22a-NeoF1 fusion protein is sorted into exosomes by HSP90 via a KFERQ-like motif (RVLFLN142) together with its binding partner PYK2. Exosomal Rab22a-NeoF1 promotes pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. Exosomal PYK2 activates RhoA in recipient osteosarcoma cells and induces STAT3 activation in recipient macrophages to increase M2 polarization. Co-immunoprecipitation, exosome isolation and characterization, KFERQ motif mutagenesis, RhoA and STAT3 activation assays, macrophage recruitment assays, lung metastasis model Signal transduction and targeted therapy High 33568623
2021 Rab22A binds to the NC-CC1 domains of KIF13A motor, relieving proline-mediated inhibition that keeps KIF13A as inactive monomers, thereby facilitating KIF13A dimerization and enabling balanced motility for recycling endosome tubulation. Single-molecule fluorescence assay, in vitro motility assays, domain mutagenesis, Co-IP of Rab22A with KIF13A domains Science advances High 33536208
2022 RAB22A mediates a non-canonical autophagy pathway: RAB22A engages PI4K2A to generate PI4P, which recruits the Atg12–Atg5–Atg16L1 complex, inducing formation of ER-derived non-canonical autophagosomes. These fuse with RAB22A-positive early endosomes to form a new organelle (Rafeesome). RAB22A inactivates RAB7 to suppress Rafeesome fusion with lysosomes, enabling secretion of activated STING-containing inner vesicles (R-EVs) that promote antitumor immunity in recipient cells. Co-immunoprecipitation, PI4P lipid assay, organelle marker colocalization, RAB7 activity assay, electron microscopy, STING agonist treatment, IFNβ secretion assay, mouse tumor model Cell research High 36280710
2022 Rab22a-NeoF1 fusion protein is degraded via a STUB1 E3-ligase–NDP52 autophagy receptor–lysosome pathway. STUB1 catalyzes K63-linked ubiquitin chains on lysine 112 of Rab22a-NeoF1, enabling NDP52 binding and lysosomal degradation. PINK1 phosphorylates Rab22a-NeoF1 at serine 120 to promote its ubiquitination and degradation. Sorafenib and regorafenib upregulate PINK1, thereby reducing Rab22a-NeoF1 levels and inhibiting osteosarcoma lung metastasis. E3 ligase screening, Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K112R, S120A), lysosome inhibitor experiments, PINK1 kinase assay, mouse osteosarcoma metastasis model Advanced science High 36529692
2022 Rab22a promotes lung adenocarcinoma proliferation, migration, and invasion by activating the PI3K/Akt/mTOR pathway. Co-IP confirmed a direct interaction between Rab22a and PI3K regulatory subunit p85α. Rapamycin (mTOR inhibitor) significantly reduces Rab22a-induced enhancement of malignant phenotypes. Co-immunoprecipitation (Rab22a–PI3Kp85α), siRNA knockdown and overexpression, Western blot for PI3K/Akt/mTOR phosphorylation, proliferation/migration/invasion assays, rapamycin inhibition Experimental cell research Medium 35487271
2023 Vps9d1, a VPS9 domain-containing protein, is a specific GEF for Rab22A that activates Rab22A but not Rab5A. Depletion of Vps9d1 severely impairs tubular endosome formation and alters clathrin-independent endocytosis cargo recycling. Expression of constitutively active Rab22A rescues tubular endosomes in Vps9d1-depleted cells, but a GEF-activity-deficient Vps9d1 mutant does not. Vps9d1 siRNA knockdown, GEF activity assay, constitutively active Rab22A rescue, Rab5A localization controls, tubular endosome imaging, CIE cargo recycling assay Journal of cell science High 36762583
2024 RAB22A recruits TBC1D2B (a GAP for RAB7A) to inactivate RAB7A, preventing EGFR from being transported to late endosomes/lysosomes. RAB22A also engages SH3BP5L (a GEF for RAB11A) to activate RAB11A on early endosomes, recycling EGFR to the cell surface for packaging into microvesicles. EGFR phosphorylates RAB22A at Tyr136, which promotes EGFR-containing MV formation. RAB GTPase family RNAi screen, Co-immunoprecipitation (RAB22A–TBC1D2B, RAB22A–SH3BP5L), RAB7A and RAB11A activity assays, EGFR phosphorylation assay (Tyr136), MV isolation and quantification Journal of extracellular vesicles High 39051763
2024 TBC1D31 acts as a RAB22A GAP that catalyzes GTP hydrolysis for RAB22A, thereby reducing RAB22A-mediated endolysosomal trafficking and degradation of EGFR and activating EGFR signaling in hepatocellular carcinoma. GAP activity assay (TBC1D31 on Rab22A), EGFR trafficking assay, Co-immunoprecipitation, in vitro and in vivo HCC models Advanced science Medium 39206796
2024 HIF-1α and RAB22A form an endogenous intracellular complex in MDA-MB-231 breast cancer cells under hypoxia, as demonstrated by co-immunoprecipitation of endogenous proteins. Transiently overexpressed HIF-1α and RAB22A did not interact, suggesting the interaction requires endogenous context. Co-immunoprecipitation of endogenous HIF-1α and RAB22A, molecular docking, transfection controls in HEK-293T cells Molecular biology reports Low 38647725
2025 RAB22A promotes exosome secretion in chemoresistant colorectal cancer cells by inhibiting ubiquitination and degradation of PKM2, which then promotes phosphorylation of SNAP-23. This RAB22A–PKM2–pSNAP-23 cascade increases exosome release, enabling intercellular chemoresistance transmission in the tumor microenvironment. Co-immunoprecipitation, ubiquitination assay, SNAP-23 phosphorylation assay, exosome isolation and quantification, conditioned medium transfer experiments, RAB22A overexpression/knockdown Oncogene Medium 40957949
2025 RAB22A interacts with the tubular ER membrane protein TMEM33, which binds RTN4 at its TM2 domain. The RAB22A/TMEM33/RTN4 assembly promotes RTN4 homo-oligomerization, generating RTN4-enriched ER membrane microdomains with high curvature that bud off as vesicles transported by ATG9A into isolation membranes anchored by LC3-II, forming sealed RTN4-positive non-canonical autophagosomes secreted as R-EVs via Rafeesome. Co-immunoprecipitation (RAB22A–TMEM33, TMEM33–RTN4), domain mutagenesis (RTN4 TM2), RTN4 oligomerization assay, organelle marker colocalization, electron microscopy, secretion assay Cell discovery High 40301304
2022 Rab22a cooperates with Rab5 and the CSFV non-structural protein NS4B during classical swine fever virus entry. Pull-down and Co-IP confirmed Rab22a–NS4B interaction; NS4B only binds wild-type Rab22a but not Q64L or S19N mutants. Rab22a colocalizes with CSFV particles in early endosomes during entry, and a Rab22a–Rab5–NS4B cascade facilitates viral entry. GST pull-down, Co-immunoprecipitation, Rab22a overexpression/knockdown/mutagenesis, confocal colocalization, viral replication assay Veterinary microbiology Medium 35134740

Source papers

Stage 0 corpus · 65 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proceedings of the National Academy of Sciences of the United States of America 420 24938788
2014 miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clinical cancer research : an official journal of the American Association for Cancer Research 179 25294901
2004 Rab22a regulates the recycling of membrane proteins internalized independently of clathrin. Molecular biology of the cell 177 15181155
2019 LncRNA SNHG3/miRNA-151a-3p/RAB22A axis regulates invasion and migration of osteosarcoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 121 30797154
2014 MicroRNA-204-5p inhibits gastric cancer cell proliferation by downregulating USP47 and RAB22A. Medical oncology (Northwood, London, England) 94 25429829
2022 Intercellular transfer of activated STING triggered by RAB22A-mediated non-canonical autophagy promotes antitumor immunity. Cell research 87 36280710
2021 Rab22a-NeoF1 fusion protein promotes osteosarcoma lung metastasis through its secretion into exosomes. Signal transduction and targeted therapy 82 33568623
2001 Rab22a affects the morphology and function of the endocytic pathway. Journal of cell science 77 11739636
2006 Rab22a regulates the sorting of transferrin to recycling endosomes. Molecular and cellular biology 74 16537905
2016 LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian cancer. Molecular medicine reports 67 27484896
2014 MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer. Oncotarget 66 25460499
2016 Rab22a controls MHC-I intracellular trafficking and antigen cross-presentation by dendritic cells. EMBO reports 54 27861124
2018 Rab22A recruits BLOC-1 and BLOC-2 to promote the biogenesis of recycling endosomes. EMBO reports 50 30404817
2020 Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma. Nature cell biology 49 32483387
2020 LncRNA ZFAS1 confers inflammatory responses and reduces cholesterol efflux in atherosclerosis through regulating miR-654-3p-ADAM10/RAB22A axis. International journal of cardiology 48 32349937
2016 MiR-211 is epigenetically regulated by DNMT1 mediated methylation and inhibits EMT of melanoma cells by targeting RAB22A. Biochemical and biophysical research communications 47 27237979
2015 miR-203 Acts as a Tumor Suppressor Gene in Osteosarcoma by Regulating RAB22A. PloS one 46 26382657
2018 Regulation of RAB22A by mir-193b inhibits breast cancer growth and metastasis mediated by exosomes. International journal of oncology 37 30272274
2022 Targeting the Lysosomal Degradation of Rab22a-NeoF1 Fusion Protein for Osteosarcoma Lung Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 32 36529692
2017 Rab22a enhances CD147 recycling and is required for lung cancer cell migration and invasion. Experimental cell research 30 28433697
2016 MiR-204 inhibits the proliferation and invasion of renal cell carcinoma by inhibiting RAB22A expression. Oncology reports 30 26883716
2014 Tumor suppressive microRNA-193b promotes breast cancer progression via targeting DNAJC13 and RAB22A. International journal of clinical and experimental pathology 30 25550792
2016 RAB22A overexpression promotes the tumor growth of melanoma. Oncotarget 23 27690221
2004 Overexpression of Rab22a hampers the transport between endosomes and the Golgi apparatus. Experimental cell research 23 15748882
2021 Circular RNA Circ0021205 Promotes Cholangiocarcinoma Progression Through MiR-204-5p/RAB22A Axis. Frontiers in cell and developmental biology 22 34012964
2021 LncRNA MCF2L-AS1 aggravates the malignant development of colorectal cancer via targeting miR-105-5p/RAB22A axis. BMC cancer 17 34592939
2021 KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell. Science advances 16 33536208
2021 LncRNA MIAT Mediates ox-LDL-Induced Endothelial Cell Injury Via miR-206/RAB22A Axis. The Journal of surgical research 16 33965771
2019 LncRNA DLEU1/microRNA-300/RAB22A axis regulates migration and invasion of breast cancer cells. European review for medical and pharmacological sciences 15 31841195
2022 Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway. Experimental cell research 14 35487271
2020 Acetylation dependent functions of Rab22a-NeoF1 Fusion Protein in Osteosarcoma. Theranostics 14 32685017
2018 Rab22a: A novel regulator of immune functions. Molecular immunology 14 29631761
2018 Differential requirement of Rab22a for the recruitment of ER-derived proteins to phagosomes and endosomes in dendritic cells. Small GTPases 13 28960134
2005 Fluorescent microscopy-based assays to study the role of Rab22a in clathrin-independent endocytosis. Methods in enzymology 13 16473591
2021 LINC01232 serves as a novel biomarker and promotes tumour progression by sponging miR-204-5p and upregulating RAB22A in clear cell renal cell carcinoma. Annals of medicine 12 34783622
2024 RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release. Journal of extracellular vesicles 11 39051763
2022 Rab22a Promotes Epithelial-Mesenchymal Transition in Papillary Thyroid Carcinoma by Activating PI3K/AKT/mTOR Signaling Pathway. BioMed research international 10 35757470
2024 Tanshinone IIA improves Alzheimer's disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis. World journal of psychiatry 9 38659601
2019 MicroRNA-193b acts as a tumor suppressor in colon cancer progression via targeting RAB22A. Experimental and therapeutic medicine 9 31007734
2024 Genomic Amplification of TBC1D31 Promotes Hepatocellular Carcinoma Through Reducing the Rab22A-Mediated Endolysosomal Trafficking and Degradation of EGFR. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39206796
2023 Circ_0091822 aggravates ox-LDL-induced endothelial cell injury through targeting the miR-661/RAB22A axis. Clinical hemorheology and microcirculation 8 36057815
2022 Circ_0007385 regulates cell proliferation, apoptosis and stemness via targeting miR-493-3p/RAB22A axis in non-small cell lung cancer. Thoracic cancer 8 34989145
2024 RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma. Aging 7 38431306
2023 miR-204 suppresses uveal melanoma cell migration and invasion through negative regulation of RAB22A. Functional & integrative genomics 6 36705739
2023 Vps9d1 regulates tubular endosome formation through specific activation of Rab22A. Journal of cell science 6 36762583
2020 Long non-coding RNA PSMA3-AS1 enhances cell proliferation, migration and invasion by regulating miR-302a-3p/RAB22A in glioma. Bioscience reports 6 32894281
2025 The assembly of RAB22A/TMEM33/RTN4 initiates a secretory ER-phagy pathway. Cell discovery 5 40301304
2023 Circular RNA circ_0029589 promotes ox-LDL-induced endothelial cell injury through regulating RAB22A by serving as a sponge of miR-1197. Clinical hemorheology and microcirculation 5 36683504
2023 Exosomal lncRNA LINC02191 Promotes Laryngeal Squamous cell Carcinoma Progression by Targeting miR-204-5p/RAB22A Axis and Regulating PI3K/Akt/mTOR Pathway. Biochemical genetics 5 37863866
2019 MicroRNA‑373 exerts anti‑tumor functions in human liver cancer by targeting Rab22a. Molecular medicine reports 5 31485646
2024 The ras-related protein RAB22A interacts with hypoxia-inducible factor 1-alpha (HIF-1α) in MDA-MB-231 breast cancer cells in hypoxia. Molecular biology reports 4 38647725
2022 Rab22a cooperates with Rab5 and NS4B in classical swine fever virus entry process. Veterinary microbiology 4 35134740
2019 MiR-520b inhibits proliferation, migration and invasion in gallbladder carcinoma by targeting RAB22A. Archives of medical science : AMS 4 33747283
2025 miRNA-204-5p acts as a tumor suppressor in gastric cancer by inhibiting cell migration, invasion, and glycolysis via the RAB22A/PI3K/AKT axis. Scientific reports 3 40796564
2025 RAB22A triggers intercellular chemoresistance transmission in colorectal cancer by promoting exosome release via the PKM2-pSNAP23 axis. Oncogene 3 40957949
2023 Circ-C16orf62 Regulates Oxidized low-density Lipoprotein-induced Apoptosis, Inflammation, Oxidative Stress and Cholesterol Accumulation of Macrophages via Mediating RAB22A Expression by Targeting miR-377. Applied biochemistry and biotechnology 3 36892682
2020 Rab22a regulates the establishment of epithelial polarity. Small GTPases 3 32281471
2025 [Effects of LncRNA SNHG20 on epithelial mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells through targeted regulation of the miR-520c-3p/RAB22A pathway]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 2 39856503
2024 Linc00239 Facilitates the Progress of Clear Cell Renal Cell Carcinoma via the miR-204-5p/RAB22A Axis. Molecular biotechnology 2 38850457
2024 A comparative study of Mentha longifolia var. asiatica and Zygophyllum arabicum ZnO nanoparticles against breast cancer targeting Rab22A gene. PloS one 2 39213285
2023 Insights into the complex interactions between Rab22a and extracellular vesicles in cancers. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2 38066108
2019 miRNA-520c-3p accelerates progression of nasopharyngeal carcinoma via targeting RAB22A. Oncology letters 1 31897193
2024 [Retracted] LncRNA HOTAIR controls the expression of Rab22a by sponging miR‑373 in ovarian cancer. Molecular medicine reports 0 39364749
2024 [High expression of miR-204-5p promotes malignant behaviors of bladder cancer cells by negatively regulating RAB22A]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 0 39623280
2023 Localization of Chicken Rab22a in Cells and Its Relationship to BF or Ii Molecules and Genes. Animals : an open access journal from MDPI 0 36766276

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