title: TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum.
abstract: In the present study, the human TEB4 is identified as a novel ER (endoplasmic reticulum)-resident ubiquitin ligase. TEB4 has homologues in many species and has a number of remarkable properties. TEB4 contains a conserved RING (really interesting new gene) finger and 13 predicted transmembrane domains. The RING finger of TEB4 and its homologues is situated at the N-terminus and has the unconventional C4HC3 configuration. The N-terminus of TEB4 is located in the cytosol. We show that the isolated TEB4 RING domain catalyses ubiquitin ligation in vitro in a reaction that is ubiquitin Lys48-specific and involves UBC7 (ubiquitin-conjugating enzyme 7). These properties are reminiscent of E3 enzymes, which are involved in ER-associated protein degradation. TEB4 is an ER degradation substrate itself, promoting its own degradation in a RING finger- and proteasome-dependent manner.
authors.affiliation: Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Gerco
authors.initials: G
authors.lastname: Hassink
authors.forename: Marjolein
authors.initials: M
authors.lastname: Kikkert
authors.forename: Sjaak
authors.initials: S
authors.lastname: van Voorden
authors.forename: Shiow-Ju
authors.initials: SJ
authors.lastname: Lee
authors.forename: Robbert
authors.initials: R
authors.lastname: Spaapen
authors.forename: Theo
authors.initials: T
authors.lastname: van Laar
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Coleman
authors.forename: Eric
authors.initials: E
authors.lastname: Bartee
authors.forename: Klaus
authors.initials: K
authors.lastname: Früh
authors.forename: Vincent
authors.initials: V
authors.lastname: Chau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Wiertz
mesh_terms: D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D008565:Membrane Proteins; D025801:Ubiquitin; C471617:UBE2G2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C504816:MARCHF6 protein, human; D044767:Ubiquitin-Protein Ligases