{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEC31A is a core structural component of the COPII coat complex that mediates export of secretory cargo from the endoplasmic reticulum. Acting in tandem with SEC13, SEC31A self‐assembles into flexible, cage‐like scaffolds that not only physically shape budding vesicles but also promote key biochemical events—such as stimulating the GTPase activity of Sar1 via its interaction with the inner coat proteins (Sec23/24)—thereby coordinating the assembly and disassembly of the COPII coat. In addition, posttranslational modifications such as phosphorylation by CK2 and ubiquitination/deubiquitination cascades further refine SEC31A’s association with ER membranes and its interaction with Sec23, ensuring efficient vesicle formation and cargo export."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSEC31A also functions as an important regulatory hub by interacting with Ca²⁺-binding proteins that modulate its behavior at ER exit sites. Notably, the Ca²⁺-dependent binding of ALG-2 to a proline-rich region in SEC31A stabilizes the outer COPII coat and influences vesicle budding kinetics. This regulatory interplay is further coordinated by additional factors such as annexin A11 and is modulated by luminal Ca²⁺ levels, which affect the recruitment and retention dynamics of SEC31A. Structural insights reveal that distinct hydrophobic pockets on ALG-2 recognize specific motifs within SEC31A, underlining a finely tuned mechanism that couples intracellular Ca²⁺ flux with COPII vesicle formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in vesicle trafficking, aberrations involving SEC31A can have oncogenic consequences. In certain tumors, chromosomal rearrangements have generated fusion genes—such as SEC31L1/ALK in inflammatory myofibroblastic tumors and SEC31A–JAK2 in classical Hodgkin lymphoma—that result in constitutively active kinases and deregulated signaling. Moreover, the specialized function of SEC31A in facilitating the export of bulky cargo like collagen links its activity to tissue morphogenesis and epithelial organization, with deficiencies in SEC31A-dependent COPII assembly contributing to developmental abnormalities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Scott M Stagg, Cemal Gürkan, Douglas M Fowler, et al. 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