TMX, a human transmembrane oxidoreductase of the thioredoxin family: the possible role in disulfide-linked protein folding in the endoplasmic reticulum

• Published in: Archives of biochemistry and biophysics Vol. 423; no. 1; pp. 81 - 87
• Main Authors: Matsuo, Yoshiyuki, Nishinaka, Yumiko, Suzuki, Shingo, Kojima, Masami, Kizaka-Kondoh, Shinae, Kondo, Norihiko, Son, Aoi, Sakakura-Nishiyama, Junko, Yamaguchi, Yoshimi, Masutani, Hiroshi, Ishii, Yasuyuki, Yodoi, Junji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2004
• Subjects: Calnexin - metabolism; Cystine - metabolism; Disulfide bond; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; HeLa Cells; Humans; Membrane Proteins - metabolism; Organ Specificity; Protein disulfide isomerase; Protein Folding; Protein Sorting Signals; Redox; Ribonucleases - metabolism; Thioredoxin; Thioredoxins - metabolism; Time Factors; Protein disulfide isomerase; Redox; Thioredoxin; Disulfide bond; Endoplasmic reticulum
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2003.11.003

Various proteins sharing thioredoxin (Trx)-like active site sequences (Cys–Xxx–Xxx–Cys) have been found and classified in the Trx superfamily. Among them, transmembrane Trx-related protein (TMX) was recently identified as a novel protein possessing an atypical active site sequence, Cys–Pro–Ala–Cys. In the present study, we describe the properties of this membranous Trx-related molecule. Endogenous TMX was detected as a protein of approximately 30
kDa with a cleavable signal peptide. TMX was enriched in membrane fractions and exhibited a similar subcellular distribution with calnexin localized in the endoplasmic reticulum (ER). The examination of membrane topology of TMX suggested that the N-terminal region containing the Trx-like domain was present in the ER lumen, where protein disulfide isomerase (PDI) was found to assist protein folding. Recombinant TMX showed PDI-like activity to refold scrambled RNase. These results indicate the possibility that TMX can modify certain molecules with its oxidoreductase activity and be involved in the redox regulation in the ER.