Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a.
UFD2a is a mammalian homolog of Saccharomyces cerevisiae Ufd2, originally described as an E4 ubiquitination factor. UFD2a belongs to the U-box family of ubiquitin ligases (E3s) and likely functions as both an E3 and E4. We have isolated and characterized the mouse gene (Ube4b) for UFD2a. A full-length (approximately 5700 ... bp) Ube4b cDNA was isolated and the corresponding gene spans >100 kb, comprising 27 exons. Luciferase reporter gene analysis of the 5(') flanking region of Ube4b revealed that nucleotides -1018 to -943 (relative to the translation initiation site) possess promoter activity. This functional sequence contains two putative Sp1 binding sites but not a TATA box. Immunoblot and immunohistochemical analyses revealed that UFD2a is expressed predominantly in the neuronal tissues. We also show that UFD2a interacts with VCP (a AAA-family ATPase) that is thought to mediate protein folding. These data implicate UFD2a in the degradation of neuronal proteins by the ubiquitin-proteasome pathway.
Mesh Terms:
Adenosine Triphosphatases, Animals, Base Sequence, Cell Cycle Proteins, DNA, Complementary, Fungal Proteins, Gene Components, Ligases, Mice, Molecular Sequence Data, Neurons, Promoter Regions, Genetic, Saccharomyces cerevisiae Proteins, Transcriptional Activation, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Adenosine Triphosphatases, Animals, Base Sequence, Cell Cycle Proteins, DNA, Complementary, Fungal Proteins, Gene Components, Ligases, Mice, Molecular Sequence Data, Neurons, Promoter Regions, Genetic, Saccharomyces cerevisiae Proteins, Transcriptional Activation, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
Biochem. Biophys. Res. Commun.
Date: Jan. 10, 2003
PubMed ID: 12504083
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