SelT, SelW, SelH, and Rdx 12: Genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family

Alexander Dikiy, Sergey V. Novoselov, Dmitri E. Fomenko, Aniruddha Sengupta, Bradley A. Carlson, Ronald L. Cerny, Krzysztof Ginalski, Nick V. Grishin, Dolph L. Hatfield, Vadim N. Gladyshev

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

Selenium is an essential trace element in many life forms due to its occurrence as a selenocysteine (Sec) residue in selenoproteins. The majority of mammalian selenoproteins, however, have no known function. Herein, we performed extensive sequence similarity searches to define and characterize a new protein family, designated Rdx, that includes mammalian selenoproteins SelW, SelV, SelT and SelH, bacterial SelW-like proteins and cysteine-containing proteins of unknown function in all three domains of life. An additional member of this family is a mammalian cysteine-containing protein, designated Rdx 12, and its fish selenoprotein orthologue. Rdx proteins are proposed to possess a thioredoxin-like fold and a conserved CxxC or CxxU (U is Sec) motif, suggesting a redox function. We cloned and characterized three mammalian members of this family, which showed distinct expression patterns in mouse tissues and different localization patterns in cells transfected with the corresponding GFP fusion proteins. By analogy to thioredoxin, Rdx proteins can use catalytic cysteine (or Sec) to form transient mixed disulfides with substrate proteins. We employed this property to identify cellular targets of Rdx proteins using affinity columns containing mutant versions of these proteins. Rdx 12 was found to interact with glutathione peroxidase 1, whereas 14-3-3 protein was identified as one of the targets of mammalian SelW, suggesting a mechanism for redox regulation of the 14-3-3 family of proteins.

Original languageEnglish (US)
Pages (from-to)6871-6882
Number of pages12
JournalBiochemistry
Volume46
Issue number23
DOIs
StatePublished - Jun 12 2007

ASJC Scopus subject areas

  • Biochemistry

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    Dikiy, A., Novoselov, S. V., Fomenko, D. E., Sengupta, A., Carlson, B. A., Cerny, R. L., Ginalski, K., Grishin, N. V., Hatfield, D. L., & Gladyshev, V. N. (2007). SelT, SelW, SelH, and Rdx 12: Genomics and molecular insights into the functions of selenoproteins of a novel thioredoxin-like family. Biochemistry, 46(23), 6871-6882. https://doi.org/10.1021/bi602462q