UBE2C (ubiquitin-conjugating enzyme E2C)

Description	The UbcH10 gene encodes a member of the E2 ubiquitin-conjugating enzyme family that is involved in the ubiquitin dependent proteolysis. In this pathway, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), together with ubiquitin ligase (E3), catalyze the covalent attachment of ubiquitin to target proteins, targeting them for degradation mediated by the 26S proteasome. The full-length UbcH10 contains 179 residues for a 19.6 kDa weight. It belongs to the class III Ubc proteins that are characterized by an NH2-terminal extension followed by the "core" Ubc fold. Like all E2 enzymes, UbcH10 contains an active site cysteine residue (position 114) that is crucial for the formation of the ubiquitin-thiolester. Alteration of this residue C(114)S strongly inhibits ubiquitination of cyclin A and Cyclin B confering a dominant-negative phenotype. Levels of UbcH10 are modulated by autoubiquitination. This process is dependent on a motif, the "destruction box" [Arg-X-X-Leu-X-X-(Leu/Ile)-X-Asp] recognized by the mitotic-specific ubiquitination machinery. A study suggests that a destruction box is present in the UbcH10 sequence and includes residues 129-132 (Arg-Thr-Ile-Leu). Interestingly an SNP is reported for the residue 129 (refSNP ID: rs7352110, alleles A/G, Arg>Gly). This would be important since any change in the putative destruction box could stabilize UbcH10 against destruction.
Expression	UbcH10 mRNA and protein are expressed at low levels in most adult normal tissues. In contrast, UbcH10 mRNA and protein are highly expressed in tumor tissues. Moreover, UbcH10 protein levels fluctuate during the cell cycle being abundant during M and early G1 phases, but decreasing in late G1, S and G2 phases.
Localisation	Nucleoplasm. Cytosol.
Function	UbcH10 is crucial for cell cycle progression during the G2/M phase, since its function is required for the destruction of mitotic cyclins and other mitosis-related substrates. UbcH10 interacts with the multiprotein complex APC (anaphase-promoting complex), which has E3 ubiquitin ligase activity, and targets for destruction substrates from the preceding mitosis (cyclin A, cyclin B, securin, geminin). Once these target proteins have been degraded, UbcH10 adds ubiquitins to itself, triggering its own destruction. As a result, the absence of UbcH10 allows the accumulation of cyclin A, which in turn contributes to the APC inactivation, providing a molecular switch that allows cells to proceed from cell division to a new round of DNA duplication. Hence, the function of UbcH10 is strictly linked to the progression of cell cycle through the M phase and the coupling of mitosis to S-phase entry via autonomous regulation of the anaphase-promoting complex.

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