Structure of Human Membrane-Associated Protein TEB4 and Its E3 Ligase Activity

TEB4(MARCH VI)is the homolog of yeast Doa10,an E3 ligase involved in ER-associated degradation.TEB4 and Doa10 are ER-resident,containing a conserved RING finger and large predicted transmembrane domains.They have an unconventional RING-CH domain near its N-terminus.The isolated 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 related to E3 enzymes,which are involved in ER-associated protein degradation.Like some E3 ligases,TEB4 may play a role in the regulation of the neurodegenerative disorders.