Meta-Biol

• Pathways

The ATPase activity of VCP is required for the retrotranslocation of Hh-C across the ER membrane (Chen et al, 2011). Although in this pathway, the VCP hexamer is shown as part of the SEL1:SYVN1:DERL2 retrotranslocon, the details, order of events and even the full complement of protein players in this process are not known. In yeast, the VCP homologue Cdc48 is associated with two additional proteins Ufd1 and Npl4 -both of which are also conserved in mammals- and this complex interacts with several ER components including derlins and the yeast SYVN1 homologue, Hrd1 (reviewed in Vembar and Brodsky, 2009). Consistent with the yeast data, VCP interacts with DERL2 by co-immunoprecipitation in HEK293 cells (Huang et al, 2013).