Extended Data Figure 6. Sequence similarities between Hrd1 and other multi-spanning ubiquitin ligases.

Multiple sequence alignment showing amino acid conservation in TMs 3-8 of Hrd1, TMs 3-8 of gp78 (also called AMFR), and TMs 9-14 of TRC8 (also called RNF139) and RNF145. On the left, Uniprot codes for individual sequences are given. Numbers after Uniprot codes indicate the depicted amino acid range. Black bars above the sequences indicate the location of the most C-terminal six transmembrane segments of human gp78 (top), and human TRC8 (bottom) as predicted by TOPCONS. Below that, amino acid numbering for Hrd1p from S. cerevisiae is given. Coloring was edited in JalView according to conservation of hydrophobicity ⁴⁹. Residues highlighted in green and with green dots are conserved among Hrd1 and gp78 molecules and are involved in the interaction of TMs 2,3, and 4 on the cytosolic side of the membrane (Extended Data Fig. 7c). Species abbreviations in Uniprot codes: YEAST S. cerevisiae, USTMA Ustilago maydis, CAPO3 Capsaspora owczarzaki, MONBE Monosiga brevicollis, AMPQE Amphimedon queenslandica, SCHMA Schistosoma mansoni, STRPU Strongylocentrotus purpuratus, CAEEL Caenorhabditis elegans, DROME Drosophila melanogaster, DANRE Danio rerio, THETB Thecamonas trahens, PLABS Plasmodiophora brassicae, ECTSI Ectocarpus siliculosus, PLAF7 Plasmodium falciparum, PARTE Paramecium tetraurelia, GUITH Guillardia theta, GALSU Galdieria sulphuraria, OSTLU Ostreococcus lucimarinus, ARATH Arabidopsis thaliana, LEIMA Leishmania major, DICDI Dictyostelium discoideum, DAPPU Daphnia pulex, CIOIN Ciona intestinalis, SELML Selaginella moellendorffii, STRMM Strigamia maritima.