{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:57:04Z","timestamp":1791082624139,"version":"4.1.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:p>I\u2212 is actively transported into thyrocytes via the Na+\/I\u2212 symporter (NIS), a key glycoprotein located on the basolateral plasma membrane. The cDNA encoding rat NIS was identified in our laboratory, where an extensive structure\/function characterization of NIS is being conducted. Several NIS mutants have been identified as causes of congenital I\u2212 transport defect (ITD), including V59E NIS. ITD is characterized by low thyroid I\u2212 uptake, low saliva\/plasma I\u2212 ratio, hypothyroidism, and goiter and may cause mental retardation if untreated. Studies of other ITD-causing NIS mutants have revealed valuable information regarding NIS structure\/function. V59E NIS was reported to exhibit as much as 30% of the activity of wild-type NIS. However, this observation was at variance with the patients\u2019 phenotype of total lack of activity. We have thoroughly characterized V59E NIS and studied several amino acid substitutions at position 59. We demonstrated that, in contrast to the previous report, V59E NIS is inactive, although it is properly targeted to the plasma membrane. Glu and all other charged amino acids or Pro at position 59 also yielded nonfunctional NIS proteins. However, I\u2212 uptake was rescued to different degrees by the other substitutions. Although the Km values for Na+ and I\u2212 were not altered in these active mutants, we found that the structural requirement for NIS function at position 59 is a neutral, helix-promoting amino acid. This result suggests that the region that contains V59 may be involved in intramembrane helix-helix interactions during the transport cycle without being in direct contact with the substrates.<\/jats:p>","DOI":"10.1210\/en.2008-0027","type":"journal-article","created":{"date-parts":[[2008,3,14]],"date-time":"2008-03-14T00:53:36Z","timestamp":1205456016000},"page":"3077-3084","source":"Crossref","is-referenced-by-count":32,"title":["Molecular Characterization of V59E NIS, a Na+\/I\u2212 Symporter Mutant that Causes Congenital I\u2212 Transport Defect"],"prefix":"10.1210","volume":"149","author":[{"given":"Mia D.","family":"Reed-Tsur","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"De la Vieja","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Ginter","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Carrasco","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2008,8,13]]},"reference":[{"key":"2020071612160345800_R1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0304-4157(93)90017-I","article-title":"Iodide transport in the thyroid gland.","volume":"1154","author":"Carrasco","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"2020071612160345800_R2","doi-asserted-by":"crossref","first-page":"27230","DOI":"10.1074\/jbc.272.43.27230","article-title":"Thyroid Na+\/I\u2212 symporter. 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