This PA domain is found in ZNRF4 /RNF13/RNF167 from animals and RMR1-6 from Arabidopsis. These proteins contain a C3H2C3 RING finger and some of them are predicted to be membrane-anchored RING finger ubiquitin ligases [, ]. ZNRF4 is an ER-localized RING finger ubiquitin ligase and a regulator of calnexin stability and ER homeostasis []. RNF13 is highly enriched in ER and serves as a critical mediator for facilitating ER stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway []. RMR1 (also known as ReMembR-H2) is a sorting receptor involved in transport of storage proteins to protein storage vacuoles [].The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors [].
