Neuronal Proteomic Analysis of the Ubiquitinated Substrates of the Disease-Linked E3 Ligases Parkin and Ube3a

Figure 2

E3 ligase types, UBE3A and Parkin. (a) Human UBE3A domain structure. Protein domain structure and amino acid numbering refer to the isoform II. UBE3A contains an AZUL (amino-terminal Zn-finger of UBE3A E3 ligase) domain, thought to play a role in substrate recognition, as well as a HECT domain (Homologue to E6AP Carboxyl Terminus) characteristic of this family of E3 ligases, which was named after its discovery in UBE3A, also known by the name E6AP. The ubiquitin ligating catalytic cysteine is found within this HECT domain. All through the rest of the sequence of UBE3A only a small region known to interact with viral protein E6 has been described. (b) Parkin domain structure. Parkin contains a N-terminal UBL domain followed by a RING-like domain (RING0) and a RBR domain. The RBR domain entails a RING1 domain, which comprises the E2 binding site, a IBR domain, and the catalytic site encompassing RING2 domain. Amino acid numbering is based on human sequences.

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