UBE2D3
UBE2D3 (ubiquitin conjugating enzyme E2 D3, also known as UbcH5C) is an E2 enzyme that accepts ubiquitin from the E1 complex and catalyses its covalent attachment to other proteins. It works with many E3 ligases in protein quality control, DNA damage responses and signalling. Browse Assay Genie's current range of UBE2D3 research reagents below, or read on for the biology behind the target.
Ubiquitination is a cellular mechanism for targeting abnormal or short-lived proteins for degradation. It involves three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). UBE2D3 is an E2. It accepts ubiquitin from the E1 complex and catalyses its attachment to substrate proteins. In vitro it catalyses 'Lys-11'- and 'Lys-48'-linked polyubiquitination.
UBE2D3 often acts as an initiator E2, priming a substrate with a single ubiquitin before other enzymes extend the chain. With the SCF(FBXW11) E3 complex, it primes phosphorylated NFKBIA at 'Lys-21' and/or 'Lys-22'. CDC34 then elongates the chain, leading to proteasomal degradation of NFKBIA. With RNF8 it primes PCNA, and PCNA ubiquitination is essential for the DNA damage tolerance pathway after UV or chemical damage in S-phase. It also associates with the BRCA1/BARD1 E3 complex at DNA damage sites after ionizing radiation, which leads to DNA repair.
The enzyme partners with other E3 ligases for distinct substrates. MDM2 and TOPORS act with it on p53/TP53. CBL acts with it on EGFR at the plasma membrane and on endosomes. STUB1 acts with it to ubiquitinate unfolded proteins and destroy them. RNF135 acts with it on 'Lys-63'-linked polyubiquitination of RIGI, which drives interferon beta production. ZNF598 acts with it on 40S ribosomal proteins after ribosome collisions. It also targets DAPK3, which influences PML nuclear body formation, and works with the GATOR2 complex on NPRL2. UBE2D3 belongs to the ubiquitin-conjugating enzyme family, and the UBE2D3 gene is in the HGNC group of E2 enzymes.
UBE2D3 primes NFKBIA with monoubiquitin for CDC34-driven chain elongation and proteasomal degradation, making it a useful node for studying E2 cooperation.
It primes PCNA with RNF8 in the DNA damage tolerance pathway and works with BRCA1/BARD1 at damage sites after ionizing radiation.
With MDM2, TOPORS and CBL, UBE2D3 contributes to ubiquitination of p53 and to EGFR handling at the plasma membrane and on endosomes.
It supports RIGI ubiquitination with RNF135 for interferon beta production, and works with STUB1 and ZNF598 in quality control.
UBE2D3 is an E2 ubiquitin-conjugating enzyme. It accepts ubiquitin from the E1 complex and, with partner E3 ligases, attaches it to substrates. It often acts as an initiator E2 that primes a target before other E2s extend the ubiquitin chain.
UBE2D3 is also called UbcH5C. Earlier names include ubiquitin-conjugating enzyme E2D 3 (homologous to yeast UBC4/5) and ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast). UniProt lists the protein as ubiquitin-conjugating enzyme E2 D3.
Mouse and rat both have a Ube2d3 ortholog. NCBI Gene notes that the enzyme functions in ubiquitination of the tumour-suppressor p53, induced by an E3 ligase. UniProt names MDM2 and TOPORS as partner E3 ligases. Check the datasheet of any product for its validated reactivity.
Other ubiquitin-conjugating E2 enzymes and ubiquitin ligases that work alongside UBE2D3 in ubiquitination pathways.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P61077; product specifications from Assay Genie datasheets.