TheUBE2L3 gene is located atchromosome 22q11.21, consisting of 6exons. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[7]
There are 38 E2 enzymes in humans.[9] They all contain a conserved catalytic coredomain that interacts with E1 and E3 and many E2s possess additional N- and/orC-terminal protein sequences.[10][11] In contrast to other E2s, residues necessary forlysine reactivity are absent: the D87 and D117 residues (inUBCH5C numbering) are replaced byPro andHis residues.[12]
The modification of proteins withubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins fordegradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). E2s play a key role in the whole ubiquitin (Ub) transfer pathway and are responsible for Ubcellular signaling. Unlike many E2s that transfer Ub with RINGs, UBE2L3 has E3-independent reactivity with lysine.[12] This enzyme is demonstrated to participate in the ubiquitination ofp53,c-Fos, and theNF-κB precursor p105 in vitro. UBE2L3 is primarily known for its role in thecell cycle. Specifically, UBE2L3 manages cell cycle regulatory protein levels via the ubiquitin proteolytic pathway (UPP) during the G1/S transition and during the actualS phase.[13]
Throughgenome-wide association studies (GWAS), UBE2L3 has been associated with several autoimmune diseases, includingRA,celiac disease,CD, andSLE via the ubiquitination of the NK-κB precursor.[13][14][15] This association was observed in European, Asian, and African-American populations.[13] UBE2L3 has been linked to natural killer cell cytotoxic function, and high UBE2L3 levels had contributed to clearing chronic HBV infection.[8][15] UBE2L3 controls the protein stability of53BP1 and determines the DNAdouble-strand break repair choice. Loss of UBE2L3 stabilizes 53BP1 and force cells to chooseNHEJ to repair DNA double-strand break. Repair by NHEJ leads to radial chromosomes and cell death.[16][17] UBE2L3 depletion may become a novel strategy in enhancing the effect of anticancer therapies.[18] The haplotype ofUBE2L3 gene is also reported associated withHashimoto's thyroiditis in a Chinese Han population.[19](27094594)
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Moynihan TP, Ardley HC, Leek JP, Thompson J, Brindle NS, Markham AF, Robinson PA (October 1996). "Characterization of a human ubiquitin-conjugating enzyme gene UBE2L3".Mamm. Genome.7 (7):520–5.doi:10.1007/s003359900155.PMID8672131.S2CID36212813.
^Moynihan TP, Cole CG, Dunham I, O'Neil L, Markham AF, Robinson PA (September 1998). "Fine-mapping, genomic organization, and transcript analysis of the human ubiquitin-conjugating enzyme gene UBE2L3".Genomics.51 (1):124–7.doi:10.1006/geno.1998.5257.PMID9693040.
^abHu Z, Liu Y, Zhai X, Dai J, Jin G, Wang L, et al. (Dec 2013). "New loci associated with chronic hepatitis B virus infection in Han Chinese".Nature Genetics.45 (12):1499–503.doi:10.1038/ng.2809.PMID24162738.S2CID23028494.
^abcdZuo XB, Sheng YJ, Hu SJ, Gao JP, Li Y, Tang HY, Tang XF, Cheng H, Yin XY, Wen LL, Sun LD, Yang S, Cui Y, Zhang XJ (2014). "Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population".Rheumatol Int.34 (4):459–64.doi:10.1007/s00296-013-2864-3.PMID24091983.S2CID22804352.
^Mitchell LJ, Moody CJ (November 2014). "Solar photochemical oxidation of alcohols using catalytic hydroquinone and copper nanoparticles under oxygen: oxidative cleavage of lignin models".The Journal of Organic Chemistry.79 (22):11091–100.doi:10.1021/jo5020917.PMID25322456.
^abAnan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, Kuwano A, Matsuda I, Endo F, Saya H, Nakao M (November 1998). "Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes".Genes Cells.3 (11):751–63.doi:10.1046/j.1365-2443.1998.00227.x.PMID9990509.S2CID1653536.
^Bruce MC, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D (October 2008). "Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain".Biochem. J.415 (1):155–63.doi:10.1042/BJ20071708.PMID18498246.
^Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM, Pavletich NP (November 1999). "Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade".Science.286 (5443):1321–6.doi:10.1126/science.286.5443.1321.PMID10558980.
Robinson PA, Leek JP, Thompson J, Carr IM, Bailey A, Moynihan TP, Coletta PL, Lench NJ, Markham AF (1995). "A human ubiquitin conjugating enzyme, L-UBC, maps in the Alzheimer's disease locus on chromosome 14q24.3".Mamm. Genome.6 (10):725–31.doi:10.1007/BF00354295.PMID8563171.S2CID9212706.
Ardley HC, Moynihan TP, Markham AF, Robinson PA (2000). "Promoter analysis of the human ubiquitin-conjugating enzyme gene family UBE2L1-4, including UBE2L3 which encodes UbcH7".Biochim. Biophys. Acta.1491 (1–3):57–64.doi:10.1016/s0167-4781(00)00024-5.PMID10760570.
