Verified Applications: Recombinant Ubiquitin Conjugating Enzyme 2L3 accepts activated ubiquitin from Ubiquitin Activating Enzyme 1 (an E1) in in vitro reactions. This charged E2 subsequently transfers ubiquitin to a catalytic cysteine found in HECT- and RBR-class E3 ligases. Appropriate enzyme concentrations are specific to the application.
2 μg UBE2L3 run on 4-12% SDS-PAGE gel under reducing conditions, then visualized with Colloidal Coomassie Blue Stain.
Formulation: 40 mM HEPES, 100 mM NaCl, 10% Glycerol, 1 mM EDTA, 1 mM TCEP, pH 7.6
Shipping: The product is shipped with dry ice or equivalent. Upon receipt, store it immediately at the temperature recommended below.
Storage and Stability: Use a manual defrost freezer and avoid repeated freeze-thaw cycles. Aliquot and store ≤ -70°C (stable for 24 months from date of receipt).
Protein Sequence: GPGSMAASRRLMKELEEIRKCGMKNFRNIQVDEANLLTWQGLIVPDNPPYDKGAFRIEINFPAEYPFKPPKITFKTKIYHPNIDEKGQVCLPVISAENWKPATKTDQVIQSLIALVNDPQPEHPLRADLAEEYSKDRKKFCKNAEEFTKKYGEKRPVD
Background Information and Alternate Names
Species & domain architecture
Human UBE2L3 is a single-domain 153-aa enzyme (calc. mass ~17 kDa) with the catalytic Cys86 embedded in the UBC fold. Crystal structures such as UBE2L3 bound to the HOIP RING1 domain (PDB 7V8F) reveal the extended “acidic loop” that positions ubiquitin (Ub) for transfer to E3 active sites.
UPS pathway role
UBE2L3 forms high-affinity thioester conjugates (UBE2L3~Ub) that dock onto RBR ligases (Parkin, ARIH1/2, HOIP) or HECT ligases (e.g., HUWE1, E6AP), priming the catalytic cysteine of the E3 and driving mono- or poly-ubiquitylation of substrates engaged by the cognate E3 complex. Its partnership with LUBAC licenses linear-Ub chain–driven NF-κB activation, whereas engagement by Parkin promotes mitochondrial quality control.
Relevance to TPD & disease biology
Autoimmune-risk haplotypes elevate UBE2L3 expression in B cells and monocytes, amplifying LUBAC-dependent NF-κB signalling and predisposing to SLE, Crohn’s disease and other disorders. Selective inhibition or hijacking of UBE2L3-E3 interfaces is being explored for targeted protein degradation and immune-modulatory therapies, making purified UBE2L3 an important benchmark enzyme in degrader discovery cascades.
References
Wang, S., et al., (2012) Genes Immun 13:380-387. PMID 22476155
Lewis, M., et al., (2015) Am J Hum Genet 96:221-232. PMID 25640675
Horn-Ghetko, D., et al., (2021) Nature 590:671-676. PMID 33536622
Zeng, Y., et al., (2022) Front Mol Biosci 9:872130. PMID 35265070
