ArticleAmerican journal of respiratory cell and molecular biology2021
Connecting COPD GWAS Genes: FAM13A Controls TGFβ2 Secretion by Modulating AP-3 Transport.
Article in American journal of respiratory cell and molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 11 citations in OpenAlex.
- Influence of FAM13A gene polymorphism and serum matrix metalloproteinases 9 and 12 on the phenotypes of chronic obstructive pulmonary disease.BMC pulmonary medicine · 2026Article
- Long isoforms of the COPD risk gene FAM13A orchestrate human lung epithelial development.American journal of respiratory cell and molecular biology · 2026Article
- Lung organoids for respiratory diseases: overcoming translational hurdles in drug discovery and safety assessment.Frontiers in bioengineering and biotechnology · 2026Review
- The multifaceted role of FAM13A in pulmonary diseases.Frontiers in genetics · 2026Review
- FAM13A polymorphism is associated with a usual interstitial pneumonia pattern in patients with systemic sclerosis-associated interstitial lung disease.Rheumatology (Oxford, England) · 2025Article
- The FAM13A Long Isoform Regulates Cilia Movement and Coordination in Airway Mucociliary Transport.American journal of respiratory cell and molecular biology · 2024Article
- Genetic Susceptibility to Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis: The Missing Link?American journal of respiratory cell and molecular biology · 2023Article
- AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex.American journal of respiratory cell and molecular biology · 2023Article
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Connecting GWAS Susceptibility Genes in COPD: Do We Need to Consider TGF-β2?American journal of respiratory cell and molecular biology · 2021Article
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9 authors at 3 institutions in 1 country.
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Abstract
Chronic obstructive pulmonary disease (COPD) is a common, complex disease and a major cause of morbidity and mortality. Although multiple genetic determinants of COPD have been implicated by genome-wide association studies (GWASs), the pathophysiological significance of these associations remains largely unknown. From a COPD protein-protein interaction network module, we selected a network path between two COPD GWAS genes for validation studies: FAM13A (family with sequence similarity 13 member A)-AP3D1-CTGF- TGFβ2. We find that TGFβ2, FAM13A, and AP3D1 (but not CTGF) form a cellular protein complex. Functional characterization suggests that this complex mediates the secretion of TGFβ2 through an AP-3 (adaptor protein 3)-dependent pathway, with FAM13A acting as a negative regulator by targeting a late stage of this transport that involves the dissociation of coat-cargo interaction. Moreover, we find that TGFβ2 is a transmembrane protein that engages the AP-3 complex for delivery to the late endosomal compartments for subsequent secretion through exosomes. These results identify a pathophysiological context that unifies the biological network role of two COPD GWAS proteins and reveal novel mechanisms of cargo transport through an intracellular pathway.
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