Affinage

RAB40A

Ras-related protein Rab-40A · UniProt Q8WXH6

Length
277 aa
Mass
31.1 kDa
Annotated
2026-06-10
10 papers in source corpus 1 papers cited in narrative 1 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 1/2 claims corpus-supported (50%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAB40A is the substrate-recognition component of a RAB40A–Cullin 5 E3 ubiquitin ligase complex that ubiquitinates the small GTPase RhoU and targets it for proteasomal degradation (PMID:26598620). Through this activity RAB40A controls RhoU protein levels, and the kinase PAK4 antagonizes RAB40A-mediated ubiquitination in a kinase-independent manner to stabilize RhoU, thereby regulating cell adhesion turnover and migration in breast cancer cells (PMID:26598620). Beyond (PMID:26598620), no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 1 step
  1. 2015 Medium

    Established that RAB40A is not merely a Rab GTPase but assembles with Cullin 5 into an E3 ubiquitin ligase that degrades RhoU, linking RAB40A to control of a migration-promoting GTPase.

    Evidence Co-immunoprecipitation, ubiquitination assays, and RhoU/PAK4 rescue and depletion experiments with phenotypic migration readout in breast cancer cells

    PMID:26598620

    Open questions at the time
    • No in vitro reconstitution of the RAB40A-Cullin 5 ligase or direct demonstration of RhoU ubiquitination by purified components
    • No structural model of substrate recognition or of the PAK4-mediated protection mechanism
    • How PAK4 sterically or competitively blocks RAB40A binding to RhoU in a kinase-independent manner is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether RAB40A targets substrates beyond RhoU, how its ligase activity is regulated, and its subcellular localization remain unresolved.
  • No additional substrates identified
  • Regulation and activation of the RAB40A-Cullin 5 complex uncharacterized
  • Localization of RAB40A not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Pathway
R-HSA-392499 Metabolism of proteins 1
Partners
CUL5PAK4RHOU
Complex memberships
RAB40A-Cullin 5 E3 ubiquitin ligase complex

Evidence

Reading pass · 1 per-paper finding extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 RAB40A forms a complex with Cullin 5 (RAB40A-Cullin 5 complex) that ubiquitinates RhoU, targeting it for degradation; PAK4 protects RhoU from this ubiquitination in a kinase-independent manner, thereby stabilizing RhoU protein levels and promoting cell adhesion turnover and migration. Co-immunoprecipitation, ubiquitination assays, RhoU rescue experiments, PAK4 depletion with phenotypic readout in breast cancer cells The Journal of cell biology Medium 26598620

Source papers

Stage 0 corpus · 10 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Sex differences in autophagy-mediated diseases: toward precision medicine. Autophagy 75 32264724
2015 PAK4 promotes kinase-independent stabilization of RhoU to modulate cell adhesion. The Journal of cell biology 63 26598620
2023 Relationship between red cell distribution width/albumin ratio and carotid plaque in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China. Cardiovascular diabetology 35 36814226
2004 Vesicle transport in oligodendrocytes: probable role of Rab40c protein. Journal of neuroscience research 33 15160388
2024 Association between red cell distribution width-and-albumin ratio and the risk of peripheral artery disease in patients with diabetes. Frontiers in endocrinology 19 38405142
2022 TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions. American journal of human genetics 15 36368327
1981 Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. VIII. The system of relative radioresistance in immature oocytes of the irradiated population ROI4. Mutation research 9 6782472
1981 Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. X. The resistance factor rar-3: genetics. Mutation research 6 6801500
1982 Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. XIV. The genetic factor rar-1: effects in immature oocytes and their inhibition by caffeine. Mutation research 3 6806648
2026 The association between red blood cell distribution width-to-albumin ratio and Helicobacter pylori seropositivity in U.S. adults: an observational study from NHANES 1999-2000 with external validation. Frontiers in nutrition 0 42221755

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