{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPHETA2, also known as IPIP27B or Ses2, is an endocytic adaptor protein that interacts with the inositol polyphosphate 5-phosphatase OCRL and its close homolog Inpp5b. Studies have shown that PHETA2, together with its closest relative PHETA1 (and the related IPIP27A/Ses1), utilizes a conserved F&H motif to bind the C-terminal region of these phosphatases. This interaction is crucial for controlling endosomal trafficking and receptor recycling pathways, mediating the delivery of receptors between early/recycling endosomes and the trans-Golgi network. Such processes are thought to be fundamental to the cellular pathology observed in Lowe syndrome and type 2 Dent disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vivo studies using zebrafish models have further established the essential roles of PHETA2 (in conjunction with PHETA1) in mediating endocytosis and ciliogenesis in renal tissues, and in regulating craniofacial development. Loss of function in these adaptor proteins leads to defects such as impaired fluid-phase endocytosis, abnormal renal ciliogenesis, and dysregulated cathepsin K activity with consequent accumulation of immature type II collagen in craniofacial cartilage. These findings underscore the broader biological impact of PHETA2 on tissue morphogenesis and suggest that perturbations in its function may contribute to the clinical manifestations of OCRL-related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Christopher J Noakes, Grace Lee, Martin Lowe "}, {"type": "b", "children": [{"type": "t", "text": "The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-08-0730"}], "href": "https://doi.org/10.1091/mbc.E10-08-0730"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21233288"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21233288"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Laura E Swan, Livia Tomasini, Michelle Pirruccello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0914658107"}], "href": "https://doi.org/10.1073/pnas.0914658107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20133602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20133602"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kristin M Ates, Tong Wang, Trevor Moreland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency in the endocytic adaptor proteins PHETA1/2 impairs renal and craniofacial development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dis Model Mech (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dmm.041913"}], "href": "https://doi.org/10.1242/dmm.041913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32152089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32152089"}]}]}]}