{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe SLC14A2 gene encodes the UT-A family of urea transporters, which play a critical role in transmembrane urea movement for maintaining body fluid balance, urine concentration, and blood pressure homeostasis. Structural analysis of SLC14A2 reveals a large gene with multiple exons that, through alternative splicing, generates several isoforms such as UT-A1, UT-A2, UT-A3, UT-A5, and UT-A6 with tissue‐specific expression patterns. Notably, UT-A1 and UT-A3 are expressed in the inner medullary collecting duct, UT-A2 in the thin descending limb and liver, UT-A5 in the testis, and UT-A6 in the colon, underscoring the broad physiological importance of SLC14A2 products."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental role in urea transport, SLC14A2 expression is finely regulated by hormonal and osmotic signals. Vasopressin, acting through the cAMP-dependent pathways (involving both protein kinase A and the Epac proteins), stimulates UT-A1 phosphorylation and triggers its accumulation at the apical plasma membrane, thereby enhancing urea permeability. Post-translational modifications, such as glycosylation and ubiquitination, further modulate UT-A1 trafficking and activity to ensure appropriate urinary concentration under varying physiological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic polymorphisms in SLC14A2 have been linked to clinical traits, including blood pressure regulation and antihypertensive treatment responses. Specific amino acid variants—for example, those resulting in Val/Ile and Ala/Thr substitutions—have been associated with differential blood pressure responses to diuretic therapy, suggesting that sequence variations in SLC14A2 can significantly influence renal function and cardiovascular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, functional characterization of novel isoforms, such as the small UT-A6 identified in human colonic mucosa, has expanded the understanding of urea transporter diversity and its extra-renal roles. In experimental settings, changes in the expression levels of UT-A1, UT-B1, and related aquaporins in tissues like uremic skin further highlight the importance of SLC14A2 in mediating fluid and solute transport in various organs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K Ranade, K D Wu, C M Hwu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation in the human urea transporter-2 is associated with variation in blood pressure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/10.19.2157"}], "href": "https://doi.org/10.1093/hmg/10.19.2157"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11590132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11590132"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Craig P Smith, Elizabeth A Potter, Robert A Fenton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a human colonic cDNA encoding a structurally novel urea transporter, hUT-A6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00363.2003"}], "href": "https://doi.org/10.1152/ajpcell.00363.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15189812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15189812"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A E Damiano, E Zotta, C Ibarra "}, {"type": "b", "children": [{"type": "t", "text": "Functional and molecular expression of AQP9 channel and UT-A transporter in normal and preeclamptic human placentas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Placenta (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.placenta.2005.11.014"}], "href": "https://doi.org/10.1016/j.placenta.2005.11.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16480766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16480766"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Janet D Klein "}, {"type": "b", "children": [{"type": "t", "text": "Expression of urea transporters and their regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Subcell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-94-017-9343-8_6"}], "href": "https://doi.org/10.1007/978-94-017-9343-8_6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25298340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25298340"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "X Hong, H Xing, Y Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Find Exp Clin Pharmacol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1358/mf.2007.29.1.1063490"}], "href": "https://doi.org/10.1358/mf.2007.29.1.1063490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17344938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17344938"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hui-Ju Tsai, Chin-Fu Hsiao, Low-Tone Ho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants of human urea transporter-2 are associated with metabolic syndrome in Asian population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chim Acta (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cca.2010.08.025"}], "href": "https://doi.org/10.1016/j.cca.2010.08.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20797394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20797394"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jeff M Sands, Mitsi A Blount "}, {"type": "b", "children": [{"type": "t", "text": "Genes and proteins of urea transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Subcell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-94-017-9343-8_4"}], "href": "https://doi.org/10.1007/978-94-017-9343-8_4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25298338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25298338"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Guangping Chen "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical properties of urea transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Subcell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/978-94-017-9343-8_7"}], "href": "https://doi.org/10.1007/978-94-017-9343-8_7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25298341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25298341"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Liyi Xie, Li Jin, Jie Feng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2017/8629783"}], "href": "https://doi.org/10.1155/2017/8629783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29279852"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29279852"}]}]}]}