title: Characterization of the mouse gene for the U-box-type ubiquitin ligase UFD2a.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kaneko
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yada
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D000251:Adenosine Triphosphatases; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000302:isolation & purification; D005656:Fungal Proteins / Q000235:genetics; D040461:Gene Components; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins; D015533:Transcriptional Activation; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; C471292:Ube4b protein, mouse; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse; D008025:Ligases; C114683:UFD2 protein, S cerevisiae