UBE2L3
Description
The UBE2L3 (ubiquitin conjugating enzyme E2 L3) is a protein-coding gene located on chromosome 22.
Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), also called UBCH7, is a protein that in humans is encoded by the UBE2L3 gene. As an E2 enzyme, UBE2L3 participates in ubiquitination to target proteins for degradation. The role of UBE2L3 in the ubiquitination of the NF-κB precursor implicated it in various major autoimmune diseases, including rheumatoid arthritis (RA), celiac disease, Crohn's disease (CD), and systemic lupus erythematosus.
== Structure ==
=== Gene === The UBE2L3 gene is located at chromosome 22q11.21, consisting of 6 exons. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
=== Protein === There are 38 E2 enzymes in humans. They all contain a conserved catalytic core domain that interacts with E1 and E3 and many E2s possess additional N- and/or C-terminal protein sequences. In contrast to other E2s, residues necessary for lysine reactivity are absent: the D87 and D117 residues (in UBCH5C numbering) are replaced by Pro and His residues.
== Function == The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s).
UBE2L3 is a ubiquitin-conjugating enzyme E2 that specifically works with HECT-type and RBR family E3 ubiquitin-protein ligases. It does not function with most RING-containing E3 ubiquitin-protein ligases due to its lack of intrinsic E3-independent reactivity with lysine. However, it does possess activity with the RBR family E3 enzymes, such as PRKN, RNF31, and ARIH1, which function like RING-HECT hybrids. It accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, it catalyzes 'Lys-11'-linked polyubiquitination. It is involved in the selective degradation of short-lived and abnormal proteins. UBE2L3 is down-regulated during the S-phase and is involved in progression through the cell cycle. It regulates nuclear hormone receptors' transcriptional activity and may play a role in myelopoiesis.
UBE2L3 is also known as E2-F1, L-UBC, UBCH7, UbcM4.