Schematic presentation of functional and structural domains of p62 and its Drosophila orthologue, Ref(2)P. (a) p62 consists of a PB1 domain (Phox and Bem1p domain) which is responsible for the interaction with the autophagy receptor NBR1 and the protein kinases ERK, MEKK3, MEK5, PKCζ, and PKCλ/ι. The PB1 domain is followed by a ZZ-type zinc finger domain which contains the binding site for RIP1 and a TB domain which harbors the binding site of TRAF6. Nuclear localization signals (NLSs) and nuclear export signal (NES) are also present. p62 contains a LIR (LC3-interacting region) and a KIR (KEAP1-interacting region) motif and a C-terminal UBA (ubiquitin associated) domain responsible for binding to ubiquitin. Ref(2)P has similar structural and functional domains compared to p62. It consists of a PB1 domain which is followed by a ZZ-type zinc finger domain and a C-terminal UBA domain responsible for binding to ubiquitin. Ref(2)P also contains putative LIR and KIR motifs. (b) Bioinformatic prediction of Ref(2)P’s putative LIR and KIR motifs and alignment with human p62’s motifs. The functional roles of putative LIR and KIR motifs of Ref(2)P have to be tested experimentally.
