{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSNX2 is a phospholipid‐binding protein that plays an integral role in endosomal protein sorting. As a component of the mammalian retromer complex, SNX2 forms alternative dimers with SNX1, and together these subunits act to recruit the Vps26‐Vps29‐Vps35 cargo–selective trimer to endosomal membranes. This sequential assembly is critical for the efficient retrieval of cargo proteins such as the cation-independent mannose 6-phosphate receptor from endosomes to the trans-Golgi network, although SNX2 and SNX1 appear to have interchangeable roles in this retrograde transport process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in classical retromer-mediated transport, SNX2 is also implicated in regulating receptor trafficking and signaling. Studies in epithelial cells have demonstrated that SNX2 localizes primarily to early endosomes where it contributes to the lysosomal sorting of internalized receptors, such as the epidermal growth factor receptor (EGFR) and receptor tyrosine kinase c-Met, thereby modulating their cell-surface expression and downstream signaling. In addition, SNX2 has been shown to interact with signaling regulators—including the guanine nucleotide exchange factor Kalirin-7—to influence actin dynamics and lamellipodia formation. These functions highlight a broader role for SNX2 in coordinating endosomal trafficking with receptor signaling, which in turn can affect cellular responses such as drug sensitivity in cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSNX2 further contributes to specialized intracellular trafficking processes beyond canonical receptor sorting. It participates in the retrograde transport of toxins, such as ricin, by acting in concert with other sorting nexins like SNX4 in a phosphatidylinositol 3-kinase-dependent pathway, and is co-opted by viruses—including influenza A virus and human respiratory syncytial virus—to facilitate viral protein trafficking and assembly. Moreover, regulatory interactions involving SNX2, such as its binding to the RNA helicase Abstrakt, indicate that its expression and function can be modulated by cellular signaling networks, thereby linking membrane trafficking to broader aspects of cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anuradha Gullapalli, Tiana A Garrett, May M Paing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e03-09-0711"}], "href": "https://doi.org/10.1091/mbc.e03-09-0711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14978220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14978220"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mohammad Abdul-Ghani, Kristin L Hartman, Johnny K Ngsee "}, {"type": "b", "children": [{"type": "t", "text": "Abstrakt interacts with and regulates the expression of sorting nexin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.20285"}], "href": "https://doi.org/10.1002/jcp.20285"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15690390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15690390"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jez G Carlton, Miriam V Bujny, Brian J Peter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin-2 is associated with tubular elements of the early endosome, but is not essential for retromer-mediated endosome-to-TGN transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02568"}], "href": "https://doi.org/10.1242/jcs.02568"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16179610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16179610"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Raul Rojas, Satoshi Kametaka, Carol R Haft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00156-06"}], "href": "https://doi.org/10.1128/MCB.00156-06"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17101778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17101778"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sigrid S Skånland, Sébastien Wälchli, Audrun Utskarpen, et al. 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