Ask about this productRelated genes to: RAB5A antibody
- Gene:
- RAB5A NIH gene
- Name:
- RAB5A, member RAS oncogene family
- Previous symbol:
- RAB5
- Synonyms:
- -
- Chromosome:
- 3p24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1990-01-22
- Date modifiied:
- 2015-06-29
Related products to: RAB5A antibody
Related articles to: RAB5A antibody
- Gain-of-function mutations in are a major cause of inherited Parkinson's disease. encodes a multidomain kinase, whose bidirectional interplay with Rab GTPases regulates critical cellular processes like lysosomal homeostasis. Certain Rabs, including Rab12 and Rab29, recruit LRRK2 to organelle membranes and stimulate its kinase activity; activated LRRK2 phosphorylates a subset of Rabs in their Switch-II motifs. Molecular basis governing selective Rab recognition by LRRK2 remains unclear. Here we structurally characterize LRRK2 interactions with representative Rab GTPases and identify three novel Rab-binding sites: site 4 for Rab8A/10, site 5 for Rab43, and site 6 for Rab5A, defining a total of six distinct binding sites that account for known LRRK2-interacting Rabs. Additionally, we elucidated the binding site of GABARAP, an ATG8 member that recruits LRRK2 to stressed lysosomes. Our findings provide a framework for therapeutic targeting of LRRK2 recruitment for Parkinson's. - Source: PubMed
Publication date: 2026/05/05
Zhu HanwenEade LiamAlessi Dario RSun Ji - Pancreatic cancer is a highly aggressive malignancy with a 5-year relative survival rate of only 13%. Current treatment options have limited efficacy, and mRNA vaccines offer a new direction for its treatment. However, how to accurately identify antigen targets that possess tumor specificity, functional relevance, and immunogenicity remains the key bottleneck restricting the clinical translation of mRNA vaccines for pancreatic cancer. Recent clinical studies have advanced KRAS mutant vaccines and personalized neoantigen mRNA vaccines, yet most rely on single antigens or highly individualized designs, limiting scalability and broader clinical applicability. In this systematic review, we integrated evidence from public databases and experimental studies to identify and evaluate 16 potential pancreatic cancer mRNA vaccine antigens (ADAM9, WNT7A, TMOD3, MET, EFNB2, TPX2, AGPS, OSBPL9, KDM5A, NRAS, SCP-1, GAGE, RAB5A, ANO6, CHMP2B, and PAK2). All candidates were initially selected based on aberrant tumor expression and further prioritized using stratification strategies incorporating antigen-presenting cell infiltration, immune-related cell death pathways such as ferroptosis and pyroptosis, and functional relevance to tumor progression. ADAM9 and PAK2 showed high expression in pancreatic cancer and strong associations with tumor proliferation, invasion, and immune regulation. SCP-1 and GAGE, as cancer-testis antigens, exhibited high tumor specificity and immunogenic potential. In addition, KDM5A and ANO6 may enhance antitumor efficacy through modulation of ferroptosis or pyroptosis. Nevertheless, several candidates remain constrained by normal tissue expression or limited mechanistic evidence. This review provides a stratified framework for antigen prioritization and highlights key challenges in pancreatic cancer mRNA vaccine development, offering guidance for future multi-antigen vaccine design and translational immunotherapy. - Source: PubMed
Publication date: 2026/04/28
Xue YuzheYu JiaqiZhou HongkunChen WeiChen QiHu LingyuLuo RunzhouChen YingjingWang XiaoguangHe Xuesong - Why some tumors respond to immunotherapy ("hot" tumors) while others remain resistant ("cold" tumors) is a central challenge in oncology. Elevated RAB5A-dependent endocytosis drives tissue fluidization during the transition to invasive breast carcinoma, but its immunological consequences are unclear. Here we show that RAB5A-driven fluidization induces a mechano-metabolic stress response that disrupts the AMPK-AKAP1-DRP1 mitochondrial fission pathway, causing mitochondrial elongation. RAB5A vesicles interact with hyperfused mitochondria and promote BAX/BAK-dependent pore formation, leading to limited mitochondrial outer membrane permeabilization. This sub-lethal event is amplified by palmitoylated GASDERMIN A oligomerization on mitochondria, establishing a positive feedback loop. The resulting release of mitochondrial DNA activates the cGAS-STING innate immune pathway and drives a hyperinflammatory state. Consequently, RAB5A-expressing tumors in immunocompetent mice grow more slowly, show increased immune infiltration, and display enhanced sensitivity to immune-checkpoint blockade in a BAX/BAK-, cGAS/STING-, and mtDNA-dependent manner. These findings connect mechanical stress, mitochondrial dynamics, and innate immunity, revealing strategies to potentiate antitumor immunotherapy. - Source: PubMed
Publication date: 2026/05/13
Palamidessi AndreaFrittoli EmanuelaCorada MonicaMartini EmanueleBarzaghi LeonardoMilanese ChiaraBeznoussenko Galina VLazzarin AlessandroBellini Edoardo NMironov Alexander ALavagnino ZenoMagni SerenaBarozzi SaraParazzoli DarioTizzoni LauraDall'Olio ValentinaCancila ValeriaRomani PatriziaDi Bona MelodyZobalova RenataBoukalova StepanaRediti MattiaMastroberardino Pier GNeuzil JiriFoiani MarcoDupont SirioTripodo ClaudioScita Giorgio - Glioblastoma (GBM) cells eliminate temozolomide (TMZ) through extracellular vesicles (EVs), a resistance mechanism independent of DNA damage repair that markedly reduces intracellular drug concentration. However, strategies to block this efflux pathway remain poorly explored. Levetiracetam (LEV), a first-line antiepileptic for GBM patients, suppresses seizures by inhibiting synaptic vesicle release, but its potential role in chemotherapeutic efflux has not been investigated. Chemical proteomics identified RAB5A and CD63 as novel LEV-binding targets, and analyses of TCGA datasets further supported their clinical relevance. Mechanistic studies combining co-immunoprecipitation, immunofluorescence, and in silico modeling revealed LEV-mediated disruption of endosomal trafficking and membrane fusion, thereby inhibiting TMZ efflux. Nanoparticle tracking analysis and electron microscopy were used to evaluate EV release, while LC-MS/MS was employed to quantify TMZ at the subcellular and intratumoral levels. Orthotopic GBM models were used to evaluate therapeutic efficacy. RAB5A and CD63 were identified as dual mediators of LEV activity. LEV competitively bound RAB5A, impairing endosomal maturation and TMZ trafficking. LEV also disrupted CD63-RAB35 interaction, promoting RAB35 proteasomal degradation and suppressing plasma membrane fusion. Collectively, LEV reduced TMZ efflux and synergistically enhanced TMZ cytotoxicity in vitro, while in orthotopic models the combination therapy inhibited tumor growth, was accompanied by immune microenvironment remodeling, and prolonged survival. - Source: PubMed
Publication date: 2026/05/06
Zhao JixingLi MingkunZhang QinranLi BoyanQi YanhuaGao ZijieWang QingtongZhao RongrongZhao HongyuZhang KailiangXue HaoLi Gang - Leishmania donovani Rab5 isoforms, LdRab5a and LdRab5b, play distinct roles in the early stages of endocytosis, with LdRab5a primarily regulating fluid-phase uptake and LdRab5b modulating receptor-mediated endocytosis. These functional differences are governed by structural variations within their GTPase domains. Here, we report the crystal structure of the GTPase domain of LdRab5a in its active, GppNHp-bound, form and compare it to the previously solved GDP-bound structure. Binding of the γ-phosphate analog induces a closed conformation of the Switch I and Switch II regions, a characteristic of the active state. Circular Dichroism and thermal stability assessments using Differential Scanning Calorimetry confirmed proper folding of the protein and revealed that guanine nucleotide and Mg binding, significantly enhanced protein stability. Furthermore, molecular dynamics simulations were conducted to explore the conformational dynamics of LdRab5a in both GDP and GppNHp-bound states. The GppNHp-bound form exhibited greater structural stability compared to the GDP-bound inactive form, with significantly reduced flexibility in the Switch I region. We also present the crystal structure of LdRab5b in its GDP-bound state. Structural analysis suggests that LdRab5b may adopt an intermediate conformation during nucleotide exchange, evidenced by weak Mg coordination and a flipped-out conformation of the Switch II residue Ala78. Comparative structural analysis with human Rab5b and Arabidopsis thaliana Ara7 reveals significant differences in helix α1, strand β2, and the positioning of the hydrophobic triad residues, indicating lineage-specific adaptations in LdRab5b. Collectively, our study provides novel insights into the structure-function relationships of Leishmania Rab5 isoforms and their differential roles in endocytic trafficking. - Source: PubMed
Publication date: 2026/05/01
Pandey DivyaZohib MuhammadChaurasia AnimeshAnsari HeraChowdhury AvishekPal Ravi KantTripathi SaritaJain AnupamBiswal Bichitra KumarSiddiqi Mohammad ImranArora Ashish