Background
The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including regulated and targeted proteosomal degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). UBE2G2 is a member of the E2 conjugating enzyme family and cloning of the human gene was first described by Katsanis and Fischer (1998). The UBE2G2 gene encodes a 165-amino-acid protein that shares 57% sequence identity with UBE2G1. UBE2G2 is involved in protein degradation, including a process known as Endoplasmic Reticulum-Associated Degradation (ERAD). UBE2G2 binds the E3 ligase GP78 and the affinity of this interaction is significantly increased by the G2BR domain on GP78. The UBE2G2/GP78 interaction results in the preassembly of Lys-48-linked ubiquitin chains on the catalytic cysteine of UBE2G2. Growth of the polyubiquitin chain is mediated by an aminolysis-based transfer reaction between two UBE2G2 proteins; a mechanism for transferring preassembled ubiquitin chains from UBE2G2 to the lysine residue in a substrate (Das et al., 2009; Li et al., 2007). The E3 ligase HRD1 interacts with UBE2G2 to form Lys-48-linked- polyubiquitin chains on the substrate 3-Hydroxy-3-MethylGlutaryl-coenzyme A Reductase (HMGR) targeting it for degradation (Kikkert et al., 2004). A C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum - TEB4 - catalyses Lys-48-linked polyubiquitylation employing UBE2G2 in vitro (Hassink et al., 2005).
References
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