{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRHBG is a member of the Amt/Mep/Rh family of ammonium transporters that plays a critical role in mediating saturable, electroneutral ammonium movement across cell membranes. In studies using heterologous expression systems and native epithelia, RHBG has been shown to facilitate bidirectional ammonium transport—functioning as an NH4⁺–H⁺ exchanger with defined kinetics—and, in some contexts, to allow CO₂ flux. These transport properties support its key roles in renal ammonia secretion, acid–base homeostasis, and pulmonary ammonium metabolism."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInvestigations into the subcellular localization of RHBG reveal that its steady-state presence at the basolateral membrane of renal distal tubule and collecting duct cells is governed by a conserved tyrosine‐based (YED) motif, which directs proper targeting and anchoring via an interaction with the adaptor protein ankyrin‑G. Disruption of this motif or its binding determinants not only delays plasma membrane delivery and reduces protein stability but also abolishes its ammonium transport function. Although some studies in human kidney tissue initially failed to detect RHBG, subsequent analyses confirmed its expression in the connecting segment and type A intercalated cells, underscoring a finely tuned post-transcriptional regulation and intracellular anchoring essential for renal acid–base homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its direct role in ammonium transport, RHBG is subject to complex regulatory mechanisms that extend its function beyond mere substrate translocation. Its expression is directly modulated by β-catenin/TCF4 signaling pathways, as demonstrated in hepatocellular and colon adenocarcinoma cell models—a regulation that may be critical under conditions of metabolic stress. Moreover, emerging evidence suggests that RHBG can function as a transceptor, engaging in protein–protein interactions (notably with the adaptor MyD88) to trigger downstream NFκB activation, thus decoupling its signaling functions from its transport activity. This dual function positions RHBG as a key integrator of metabolic and intracellular signaling responses in both physiological and pathological contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Uwe Ludewig "}, {"type": "b", "children": [{"type": "t", "text": "Electroneutral ammonium transport by basolateral rhesus B glycoprotein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2004.067728"}], "href": "https://doi.org/10.1113/jphysiol.2004.067728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15284342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15284342"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nedjma Zidi-Yahiaoui, Isabelle Mouro-Chanteloup, Anne-Marie D'Ambrosio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human Rhesus B and Rhesus C glycoproteins: properties of facilitated ammonium transport in recombinant kidney cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20050657"}], "href": "https://doi.org/10.1042/BJ20050657"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15929723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15929723"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "I David Weiner, Jill W Verlander "}, {"type": "b", "children": [{"type": "t", "text": "Ammonia transport in the kidney by Rhesus glycoproteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00013.2014"}], "href": "https://doi.org/10.1152/ajprenal.00013.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24647713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24647713"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ki-Hwan Han, Kavya Mekala, Venetia Babida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the gas-transporting proteins, Rh B glycoprotein and Rh C glycoprotein, in the murine lung."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.90524.2008"}], "href": "https://doi.org/10.1152/ajplung.90524.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19429772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19429772"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R Ryan Geyer, Mark D Parker, Ashley M Toye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relative CO₂/NH₃ permeabilities of human RhAG, RhBG and RhCG."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Membr Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00232-013-9593-0"}], "href": "https://doi.org/10.1007/s00232-013-9593-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24077989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24077989"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Claude Lopez, Sylvain Métral, Dominique Eladari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ammonium transporter RhBG: requirement of a tyrosine-based signal and ankyrin-G for basolateral targeting and membrane anchorage in polarized kidney epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413351200"}], "href": "https://doi.org/10.1074/jbc.M413351200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15611082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15611082"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Alice C N Brown, Dalila Hallouane, William J Mawby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RhCG is the major putative ammonia transporter expressed in the human kidney, and RhBG is not expressed at detectable levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00013.2009"}], "href": "https://doi.org/10.1152/ajprenal.00013.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19357182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19357182"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Ki-Hwan Han, Hyun-Wook Lee, Mary E Handlogten, et al. 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