{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSNX17 is an endosomal adaptor protein defined by its conserved phox homology (PX) domain, which mediates binding to phosphatidylinositol‑3‑phosphate–rich membranes, and a distinctive truncated FERM domain with a unique C‑terminal region that enables cargo recognition. Through these domains, SNX17 directly engages NPXY or NPXF motifs present in the cytoplasmic tails of various transmembrane receptors—including integrins, low‐density lipoprotein (LDL)‐receptor family members, and P‑selectin—in order to retrieve them from lysosomal degradation and promote their recycling. This function has been demonstrated in the context of integrin stabilization and recycling, as well as the recycling of receptors such as LRP, where loss of SNX17 results in increased lysosomal targeting."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in receptor recycling, SNX17 modulates receptor signaling by stabilizing receptor levels and controlling downstream processing. For example, by binding to the YXNPXY motif within the amyloid precursor protein (APP) cytoplasmic domain, SNX17 sustains APP steady‑state levels and limits amyloid‑beta peptide production. Similarly, SNX17 interacts with the endocytic motifs of receptors such as ApoER2—thereby facilitating receptor recycling and regulating their half‑life—and binds to intracellular proteins like KRIT1 to impact integrin‐dependent cell adhesion processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSNX17 also plays a role in regulating the cell surface presentation of key signaling molecules in other systems. In T lymphocytes, SNX17 helps maintain optimal surface levels of the T cell receptor and integrins, thus facilitating effective immune synapse formation and T cell activation. Moreover, SNX17 has been implicated in the infectious entry of papillomaviruses through its interaction with the L2 capsid protein, a step important for capsid disassembly and genome delivery, and in the maintenance of centriolar satellite protein homeostasis—thereby influencing ciliogenesis under conditions of serum starvation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Peter Knauth, Thomas Schlüter, Martin Czubayko, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin 17 facilitates LRP recycling in the early endosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600756"}], "href": "https://doi.org/10.1038/sj.emboj.7600756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16052210"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16052210"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Florian Steinberg, Kate J Heesom, Mark D Bass, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201111121"}], "href": "https://doi.org/10.1083/jcb.201111121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22492727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22492727"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martin Czubayko, Peter Knauth, Thomas Schlüter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin 17, a non-self-assembling and a PtdIns(3)P high class affinity protein, interacts with the cerebral cavernous malformation related protein KRIT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.04.129"}], "href": "https://doi.org/10.1016/j.bbrc.2006.04.129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16712798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16712798"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jiyeon Lee, Claudio Retamal, Loreto Cuitiño, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800642200"}], "href": "https://doi.org/10.1074/jbc.M800642200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18276590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18276590"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Pablo Sotelo, Pamela Farfán, María Luisa Benitez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Structural determinants for binding of sorting nexin 17 (SNX17) to the cytoplasmic adaptor protein Krev interaction trapped 1 (KRIT1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.584011"}], "href": "https://doi.org/10.1074/jbc.M114.584011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25059659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25059659"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Martina Bergant, Lawrence Banks "}, {"type": "b", "children": [{"type": "t", "text": "SNX17 facilitates infection with diverse papillomavirus types."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01991-12"}], "href": "https://doi.org/10.1128/JVI.01991-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23115288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23115288"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Douglas G Osborne, Joshua T Piotrowski, Christopher J Dick, et al. 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