{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DIPK2A, also known as divergent protein kinase domain 2A and referred to in some studies as C3orf58 or DIA1, is a member of a novel kinase‐like family that appears to function within the secretory pathway. Several lines of evidence suggest that DIPK2A plays a role in regulating protein phosphorylation events that influence intracellular trafficking and the processing of secreted proteins. For example, phosphoproteomic studies in cells overexpressing DIA1/C3orf58 have revealed that its presence alters a broad spectrum of phosphorylation sites—many of which are consistent with substrates of CK2 and proline‐directed kinases—supporting a role in modulating secretory pathway dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, DIPK2A is implicated in the regulation of cell differentiation and intercellular signaling. A circular RNA derived from the transcript of DIPK2A (circ_0067680) is up‐regulated during osteogenic differentiation of human bone marrow–derived mesenchymal stem cells, and this circRNA functions as a competing endogenous RNA to modulate the Wnt/β‐catenin signaling pathway; its deficiency impairs osteoblastic differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Such findings underscore its potential involvement in the fine tuning of pathways critical for biomineralization, lipid homeostasis, wound healing, and cell migration.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, genetic studies have associated mutations or altered expression of DIPK2A (and its paralogue DIA1R) with neurodevelopmental disorders including autism spectrum disorders and X‐linked mental retardation. These observations support the notion that DIPK2A may contribute to the regulation of molecular traffic within the secretory pathway in diverse tissues, including the brain, where precise control of synaptic protein secretion is essential for normal neuronal function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the available evidence positions DIPK2A as a kinase‐like modulator of protein phosphorylation in the secretory pathway with roles extending from extracellular matrix formation and osteoblastic differentiation to the possible regulation of neural signaling processes. Further studies on its substrates and signaling pathways may reveal new insights into its contributions to both normal physiology and human disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Agnieszka Hareza, Magda Bakun, Bianka Świderska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphoproteomic insights into processes influenced by the kinase-like protein DIA1/C3orf58."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PeerJ (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7717/peerj.4599"}], "href": "https://doi.org/10.7717/peerj.4599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29666759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29666759"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuansheng Huang, Su Wan, Min Yang "}, {"type": "b", "children": [{"type": "t", "text": "Circ_0067680 expedites the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through miR-4429/CTNNB1/Wnt/β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Direct (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13062-021-00302-w"}], "href": "https://doi.org/10.1186/s13062-021-00302-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34649595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34649595"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Azhari Aziz, Sean P Harrop, Naomi E Bishop "}, {"type": "b", "children": [{"type": "t", "text": "DIA1R is an X-linked gene related to Deleted In Autism-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0014534"}], "href": "https://doi.org/10.1371/journal.pone.0014534"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21264219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21264219"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Małgorzata Dudkiewicz, Anna Lenart, Krzysztof Pawłowski "}, {"type": "b", "children": [{"type": "t", "text": "A novel predicted calcium-regulated kinase family implicated in neurological disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0066427"}], "href": "https://doi.org/10.1371/journal.pone.0066427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23840464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23840464"}]}]}]}