Background
The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including regulated and targeted proteasomal 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 is 2.9-kb and 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). Binding of UBE2G2 to the E3 ligase GP78 via the G2BR domain significantly increases the affinity of UBE2G2 for 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
Das R, Mariano J, Tsai YC, Kalathur RC, Kostova Z, Li J, Tarasov SG, McFeeters RL, Altieri AS, Ji X, Byrd RA, Weissman AM. (2009) Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Mol Cell 34, 674-85.
Hassink G, Kikkert M, Voorden SV, Lee SJ, Spaapen R, Laar TV, Coleman CS, Bartee E, Fruh K, Chau V, Wiertz V. (2005) TEB4 is a C4HC3 RING finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem J 388, 647-55.
Katsanis N, Fisher EM (1998) Identification, expression, and chromosomal localization of ubiquitin conjugating enzyme 7 (UBE2G2), a human homologue of the Saccharomyces cerevisiae ubc7 gene. Genomics 51, 128-31.
Kikkert M, Doolman R, Dai M, Avner R, Hassink G, Voorden SV, Thanedar S, Roitelman J, Chau V, Wiertz E. (2004) Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem 279, 3525-34.
Li W, Tu D, Brunger AT, Ye Y (2007) A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate. Nature 446, 333-7.