TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum.
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.
Hassink
Gerco
G
Department of Medical Microbiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Kikkert
Marjolein
M
van Voorden
Sjaak
S
Lee
Shiow-Ju
SJ
Spaapen
Robbert
R
van Laar
Theo
T
Coleman
Catherine S
CS
Bartee
Eric
E
Früh
Klaus
K
Chau
Vincent
V
Wiertz
Emmanuel
E
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
D008565:Membrane Proteins; D025801:Ubiquitin; C471617:UBE2G2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C504816:MARCHF6 protein, human; D044767:Ubiquitin-Protein Ligases