Affinage

TBC1D22B

TBC1 domain family member 22B · UniProt Q9NU19

Length
505 aa
Mass
59.1 kDa
Annotated
2026-06-10
7 papers in source corpus 5 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TBC1D22B is a Golgi-associated RAB-GTPase-activating protein (GAP) that controls membrane trafficking by inactivating specific RAB GTPases (PMID:40878439, PMID:41833373). It acts as a GAP for RAB1B, and its overexpression inhibits ER-to-Golgi transport in a manner dependent on intact GAP activity; silencing RAB1B phenocopies this trafficking defect, and the resulting altered secretory state represses a module of extracellular matrix and adhesion genes (PMID:40878439). TBC1D22B additionally targets the Golgi-resident GTPase RAB30, and through this activity it is required for normal tubular endosome formation and clathrin-independent endocytic cargo trafficking, with a downstream RAB30-BICD2-KIF5B axis implicated; both loss and excess of TBC1D22B disrupt tubular endosome structures in a GAP-dependent manner (PMID:40241313, PMID:41833373). TBC1D22B associates with the Golgi adaptor ACBD3, binding the same region used by PI4KB such that the two interactions are mutually exclusive (PMID:23572552). In triple-negative breast cancer cells, elevated TBC1D22B expression drives a glycolytic phenotype (PMID:39231952).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2013 Medium

    Established the first physical interactor of TBC1D22B, placing it at the Golgi adaptor ACBD3 and revealing it competes with the lipid kinase PI4KB for the same binding site.

    Evidence Affinity purification-mass spectrometry with fine-scale domain mapping and competitive binding assays

    PMID:23572552

    Open questions at the time
    • Functional consequence of TBC1D22B-ACBD3 binding not tested
    • GAP substrate and enzymatic role not yet defined here
    • Whether competition with PI4KB regulates PI4P signaling unaddressed
  2. 2024 Medium

    Linked TBC1D22B expression to cellular metabolism, showing its elevation drives a glycolytic phenotype in cancer cells.

    Evidence Knockdown/overexpression in TNBC cell lines with metabolic and transcriptomic/metabolomic readouts

    PMID:39231952

    Open questions at the time
    • Mechanistic connection between GAP/trafficking activity and glycolysis not resolved
    • Single cancer context (TNBC); generality unknown
  3. 2025 High

    Defined TBC1D22B as a GAP for RAB1B that gates ER-to-Golgi trafficking, providing the first direct enzymatic substrate and a secretory-pathway role tied to ECM/adhesion gene regulation.

    Evidence RUSH trafficking assay, proximity-labeling and co-IP proteomics, siRNA, GAP-dead mutagenesis, and transcriptomics

    PMID:40878439

    Open questions at the time
    • Direct biochemical GAP kinetics on RAB1B not quantified in narrative terms
    • How ECM/adhesion gene repression couples mechanistically to trafficking unresolved
  4. 2025 Medium

    Identified a role for TBC1D22B in endosomal membrane shaping, showing it is required for tubular endosome formation via its GAP activity.

    Evidence Systematic TBC/Rab-GAP siRNA screen with overexpression and tubular endosome morphology quantification in HeLa cells

    PMID:40241313

    Open questions at the time
    • The relevant Rab substrate for this endosomal phenotype not identified in this study
    • Bidirectional (knockdown and overexpression) disruption mechanism unexplained
  5. 2026 Medium

    Identified RAB30 as a second GAP substrate of TBC1D22B and placed it in a motor-based axis controlling tubular endosomes and CIE cargo recycling.

    Evidence Comprehensive Rab knockdown and dominant-negative screen with TBC1D22B epistasis in HeLa cells

    PMID:41833373

    Open questions at the time
    • Direct biochemical GAP activity on RAB30 vs RAB1B selectivity not dissected
    • RAB30-BICD2-KIF5B axis is implicated but not biochemically reconstituted
    • Relationship between RAB1B and RAB30 regulation by the same GAP unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TBC1D22B selects among RAB substrates (RAB1B vs RAB30) across compartments, and how its trafficking function connects to the glycolytic and ECM phenotypes, remains unresolved.
  • No structural model of GAP-substrate or ACBD3 interaction
  • Mechanistic link between trafficking control and metabolic reprogramming undefined
  • Physiological/in vivo role not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005768 endosome 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 2
Partners
ACBD3RAB1BRAB30

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 TBC1D22B (and paralog TBC1D22A) were identified as ACBD3-interacting proteins via affinity purification-mass spectrometry. Fine-scale mapping showed that the binding domains for TBC1D22A/B and PI4KB on ACBD3 are identical, and affinity purification confirmed that PI4KB and TBC1D22A/B interactions with ACBD3 are mutually exclusive, suggesting TBC1D22B competes with PI4KB for ACBD3 binding. Affinity purification-mass spectrometry, fine-scale domain mapping, competitive binding assays mBio Medium 23572552
2025 TBC1D22B functions as a GTPase-activating protein (GAP) for RAB1B; overexpression of TBC1D22B inhibits ER-to-Golgi transport in a GAP-activity-dependent manner, RAB1B silencing phenocopies the trafficking defects caused by TBC1D22B overexpression, and TBC1D22B overexpression represses a module of extracellular matrix and adhesion-related genes consistent with altered secretory activity. RUSH (Retention Using Selective Hooks) trafficking assay, proximity-labeling and co-immunoprecipitation proteomics, siRNA knockdown, transcriptomic profiling, GAP-dead mutant analysis Advanced science (Weinheim, Baden-Wurttemberg, Germany) High 40878439
2024 Elevated TBC1D22B expression is causally linked to a glycolytic phenotype in triple-negative breast cancer (TNBC) cell lines, as demonstrated by in-depth functional investigations. Gene knockdown/overexpression in TNBC cell lines with metabolic phenotype readout; orthogonal transcriptomics/metabolomics Cell death & disease Medium 39231952
2025 TBC1D22B is required for tubular endosome formation in HeLa cells; both knockdown and overexpression of TBC1D22B reduce tubular endosome structures, and this effect is dependent on GAP activity. Comprehensive TBC/Rab-GAP siRNA knockdown screening, overexpression experiments, tubular endosome morphology quantification Traffic (Copenhagen, Denmark) Medium 40241313
2026 RAB30, a Golgi-resident Rab GTPase, is a direct target of TBC1D22B's GAP activity and is involved in tubular endosome formation and clathrin-independent endocytosis (CIE) cargo trafficking; a Rab30-BICD2-KIF5B axis is implicated downstream. Comprehensive Rab knockdown screening, dominant-negative Rab expression, co-functional epistasis with TBC1D22B in HeLa cells Cell structure and function Medium 41833373

Source papers

Stage 0 corpus · 7 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 ACBD3 interaction with TBC1 domain 22 protein is differentially affected by enteroviral and kobuviral 3A protein binding. mBio 57 23572552
2020 Association of germline genetic variants with TMPRSS2-ERG fusion status in prostate cancer. Oncotarget 13 32341752
2024 TBC1 domain-containing proteins are frequently involved in triple-negative breast cancers in connection with the induction of a glycolytic phenotype. Cell death & disease 4 39231952
2025 TBC1D22B Regulates ER-to-Golgi Trafficking via RAB1B Inactivation and Promotes Oncogenic Programs in Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40878439
2025 Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism. Journal of thrombosis and haemostasis : JTH 1 39848545
2025 Identification of Rab GTPase-Activating Proteins Required for Tubular Endosome Formation. Traffic (Copenhagen, Denmark) 1 40241313
2026 Identification of Rab30 as a novel regulator of tubular endosomes. Cell structure and function 0 41833373

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