{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSNX6 is a multifunctional sorting nexin that acts as a critical subunit of the mammromeric retromer complex. It forms a stable, endosomally associated complex together with SNX1 (and functionally with SNX5) to mediate the retrograde transport of cargoes—most notably the cation-independent mannose-6-phosphate receptor—from endosomes to the trans‐Golgi network. In addition, SNX6 recruits molecular motor components by interacting directly with the p150(Glued) subunit of the dynein/dynactin complex, thereby driving the formation and movement of cargo‐enriched tubular endosomal intermediates. SNX6 also binds Rab32, linking it to the Golgi-associated retromer trafficking machinery and suggesting connections with LRRK2‐regulated pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in endosomal sorting, SNX6 influences receptor-mediated signaling and proteolytic processing events. Through its interaction with beta-site APP cleaving enzyme-1 (BACE1), SNX6 modulates the retrograde trafficking and overall cellular levels of BACE1, thereby negatively regulating the cleavage of the amyloid precursor protein and subsequent amyloid beta biogenesis. SNX6 also engages with the insulin-like growth factor 1 receptor (IGF1R), where it facilitates the assembly of adaptor protein complexes that promote ERK1/2 phosphorylation and may impact Akt signaling, underscoring its role in fine-tuning intracellular signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSNX6 functions further extend to the regulation of nuclear trafficking and tumor biology. It directly interacts with lamin A, promoting its delivery from the endoplasmic reticulum to the nuclear envelope via a RAN-GTP-dependent mechanism, thereby influencing nuclear envelope assembly and stability. Additionally, SNX6 associates with nuclear partners, such as BRMS1, enhancing transcriptional repression and modulating TGF-β-induced epithelial-to-mesenchymal transition—a process implicated in the aggressive behavior of pancreatic cancer. SNX6 also stabilizes PD-L1 protein levels by interfering with Cullin3-mediated ubiquitination, which may contribute to tumor immune evasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Wassmer, Naomi Attar, Miriam V Bujny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A loss-of-function screen reveals SNX5 and SNX6 as potential components of the mammalian retromer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.03302"}], "href": "https://doi.org/10.1242/jcs.03302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17148574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17148574"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhi Hong, Yanrui Yang, Cheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2009.130"}], "href": "https://doi.org/10.1038/cr.2009.130"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19935774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19935774"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Boris Simonetti, Blessy Paul, Karina Chaudhari, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Rab32 interacts with SNX6 and affects retromer-dependent Golgi trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0208889"}], "href": "https://doi.org/10.1371/journal.pone.0208889"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30640902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30640902"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hirokazu Okada, Wenzhu Zhang, Corrinne Peterhoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-146357"}], "href": "https://doi.org/10.1096/fj.09-146357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20354142"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20354142"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Akshay Bareja, Conrad P Hodgkinson, Erik Soderblom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The proximity-labeling technique BioID identifies sorting nexin 6 as a member of the insulin-like growth factor 1 (IGF1)-IGF1 receptor pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.002406"}], "href": "https://doi.org/10.1074/jbc.RA118.002406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29530981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29530981"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "José Rivera, Diego Megías, Jerónimo Bravo "}, {"type": "b", "children": [{"type": "t", "text": "Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.22874"}], "href": "https://doi.org/10.1002/jcb.22874"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20830743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20830743"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Pengfei Hu, Yun Liang, Qiangsheng Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNX6 predicts poor prognosis and contributes to the metastasis of pancreatic cancer cells via activating epithelial-mesenchymal transition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmy110"}], "href": "https://doi.org/10.1093/abbs/gmy110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30307473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30307473"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jose M González-Granado, Ana Navarro-Puche, Pedro Molina-Sanchez, et al. 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