{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nFAM105A, also known as OTULINL, is a unique member of the ovarian tumor (OTU) protease family in humans that, due to key structural deficiencies in its OTU domain, lacks conventional deubiquitinase (DUB) activity. Instead of catalyzing ubiquitin removal from substrates, its impaired active site and substrate‐binding regions suggest that FAM105A mediates its cellular functions primarily through protein–protein interactions. This is further supported by its subcellular localization, as it co-localizes with endoplasmic reticulum and nuclear envelope markers and interacts predominantly with proteins found in the ER, Golgi, and vesicular membranes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its proposed scaffolding and regulatory roles stemming from its interaction profile, FAM105A plays an important role in pancreatic β-cell physiology. Studies in human islets and insulin-secreting cells have shown that FAM105A is highly expressed under normal conditions but is markedly reduced in islets from diabetic donors. Reduced expression is associated with diminished insulin secretion, content, glucose uptake, and mitochondrial ATP production. Moreover, FAM105A silencing leads to downregulation of key β-cell transcription factors and glucose transporters, indicating that it contributes to maintaining β-cell function and may influence the pathogenesis of type 2 diabetes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Derek F Ceccarelli, Sofiia Ivantsiv, Amber Anne Mullin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2019.03.022"}], "href": "https://doi.org/10.1016/j.str.2019.03.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31056421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31056421"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jalal Taneera, Anila Khalique, Aissaoui Salima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disrupting of family with sequence similarity 105, member A (Fam105a) deteriorates pancreatic β-cell physiology and insulin secretion in INS-1 cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2023.111987"}], "href": "https://doi.org/10.1016/j.mce.2023.111987"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37311518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37311518"}]}]}]}