InterPro domain: IPR044744

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 [ 1 , 2 ]. ZNRF4 is an ER-localized RING finger ubiquitin ligase and a regulator of calnexin stability and ER homeostasis [ 3 ]. 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 [ 3 ]. RMR1 (also known as ReMembR-H2) is a sorting receptor involved in transport of storage proteins to protein storage vacuoles [ 4 ].

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 [ 5 ].

1. The PA-TM-RING protein RING finger protein 13 is an endosomal integral membrane E3 ubiquitin ligase whose RING finger domain is released to the cytoplasm by proteolysis. FEBS J 276, 1860-77
2. A systematic search for endoplasmic reticulum (ER) membrane-associated RING finger proteins identifies Nixin/ZNRF4 as a regulator of calnexin stability and ER homeostasis. J Biol Chem 286
3. RNF13, a RING finger protein, mediates endoplasmic reticulum stress-induced apoptosis through the inositol-requiring enzyme (IRE1α)/c-Jun NH2-terminal kinase pathway. J Biol Chem 288, 8633-43
4. AtRMR1 functions as a cargo receptor for protein trafficking to the protein storage vacuole. J Cell Biol 170, 757-67
5. The protease-associated domain: a homology domain associated with multiple classes of proteases. Trends Biochem. Sci. 26, 147-8