UBE2L3

Ubiquitin-conjugating enzyme E2 L3 is a protein that in humans is encoded by the UBE2L3 gene. As an E2 enzyme, UBCH7 participates in ubiquitination to target proteins for degradation. The role of UBCH7 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.

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). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-κB precursor p105 in vitro. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. UBE2L3 is primarily known for its role in the cell cycle. Specifically, UBE2L3 manages cell cycle regulatory protein levels via the ubiquitin proteolytic pathway (UPP) during the G1/S transition and during the actual S phase.

Clinical significance

Through genome-wide association studies (GWAS), UBE2L3 has been associated with several autoimmune diseases, including RA, celiac disease, CD, and SLE via the ubiquitination of the NK-κB precursor. This association was observed in European, Asian, and African-American populations. UBE2L3 has also been linked to natural killer cell cytotoxic function, and high UBE2L3 levels had contributed to clearing chronic HBV infection.

Interactions

UBE2L3 has been shown to interact with:

• ARIH1,
• ARIH2,
• CBL,
• CHEK1,
• NEDD4,
• PARK2,
• SMURF2,
• TNFAIP3,
• TNFSF4,
• TNIP1,
• TRAF6,
• UBE3A,
• UBE3A, and
• UBOX5.