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Ubiquitin-conjugating enzyme E2L 3
Protein UBE2L3 PDB 1c4z.png
PDB rendering based on 1c4z.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols UBE2L3 ; E2-F1; L-UBC; UBCH7; UbcM4
External IDs OMIM603721 MGI109240 HomoloGene43226 GeneCards: UBE2L3 Gene
EC number
RNA expression pattern
PBB GE UBE2L3 200682 s at tn.png
PBB GE UBE2L3 200676 s at tn.png
PBB GE UBE2L3 200683 s at tn.png
More reference expression data
Species Human Mouse
Entrez 7332 22195
Ensembl ENSG00000185651 ENSMUSG00000038965
UniProt P68036 P68037
RefSeq (mRNA) NM_001256355 NM_009456
RefSeq (protein) NP_001243284 NP_033482
Location (UCSC) Chr 22:
21.55 – 21.62 Mb
Chr 16:
17.15 – 17.2 Mb
PubMed search [1] [2]

Ubiquitin-conjugating enzyme E2 L3 is a protein that in humans is encoded by the UBE2L3 gene.[1][2][3] As an E2 enzyme, UBCH7 participates in ubiquitination to target proteins for degradation.[3] The role of UBCH7 in the ubiquitination of the NF-kB precursor implicated it in various major autoimmune diseases, including rheumatoid arthritis (RA), celiac disease, Crohn’s disease(CD), and systemic lupus erythematosus.[4]


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.[3] 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.[5]

Clinical significance[edit]

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.[6][5][7] This association was observed in European, Asian, and African-American populations.[5] UBE2L3 has also been linked to natural killer cell cytotoxic function, and high UBE2L3 levels had contributed to clearing chronic HBV infection.[7][4]


UBE2L3 has been shown to interact with:


  1. ^ Moynihan TP, Ardley HC, Leek JP, Thompson J, Brindle NS, Markham AF et al. (October 1996). "Characterization of a human ubiquitin-conjugating enzyme gene UBE2L3". Mamm. Genome 7 (7): 520–5. doi:10.1007/s003359900155. PMID 8672131. 
  2. ^ 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. PMID 9693040. 
  3. ^ a b c "Entrez Gene: UBE2L3 ubiquitin-conjugating enzyme E2L 3". 
  4. ^ a b Hu 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. PMID 24162738. 
  5. ^ a b c Wang S, Adrianto I, Wiley GB, Lessard CJ, Kelly JA, Adler AJ et al. (Jul 2012). "A functional haplotype of UBE2L3 confers risk for systemic lupus erythematosus". Genes and Immunity 13 (5): 380–7. doi:10.1038/gene.2012.6. PMID 22476155. 
  6. ^ a b c d Morlacchi F, Armenise D, Losacco V, Trapani G (Sep 1985). "[Quantitative microbiologic determination of organophosphorus compounds]". Bollettino Chimico Farmaceutico 124 (9): 387–92. PMID 4091983. 
  7. ^ a b Fransen K, Visschedijk MC, van Sommeren S, Fu JY, Franke L, Festen EA et al. (Sep 2010). "Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn's disease". Human Molecular Genetics 19 (17): 3482–8. doi:10.1093/hmg/ddq264. PMID 20601676. 
  8. ^ Tan NG, Ardley HC, Scott GB, Rose SA, Markham AF, Robinson PA (November 2003). "Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP". FEBS Lett. 554 (3): 501–4. doi:10.1016/s0014-5793(03)01235-3. PMID 14623119. 
  9. ^ Moynihan TP, Ardley HC, Nuber U, Rose SA, Jones PF, Markham AF et al. (October 1999). "The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1". J. Biol. Chem. 274 (43): 30963–8. doi:10.1074/jbc.274.43.30963. PMID 10521492. 
  10. ^ Ardley HC, Tan NG, Rose SA, Markham AF, Robinson PA (June 2001). "Features of the parkin/ariadne-like ubiquitin ligase, HHARI, that regulate its interaction with the ubiquitin-conjugating enzyme, Ubch7". J. Biol. Chem. 276 (22): 19640–7. doi:10.1074/jbc.M011028200. PMID 11278816. 
  11. ^ a b c d e f Whitcomb EA, Dudek EJ, Liu Q, Taylor A (Jan 2009). "Novel control of S phase of the cell cycle by ubiquitin-conjugating enzyme H7". Molecular Biology of the Cell 20 (1): 1–9. doi:10.1091/mbc.E08-01-0036. PMID 18946090. 
  12. ^ Yokouchi M, Kondo T, Houghton A, Bartkiewicz M, Horne WC, Zhang H et al. (October 1999). "Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7". J. Biol. Chem. 274 (44): 31707–12. doi:10.1074/jbc.274.44.31707. PMID 10531381. 
  13. ^ Zheng N, Wang P, Jeffrey PD, Pavletich NP (August 2000). "Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases". Cell 102 (4): 533–9. doi:10.1016/S0092-8674(00)00057-X. PMID 10966114. 
  14. ^ Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY et al. (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". EMBO J. 21 (18): 4796–808. doi:10.1093/emboj/cdf493. PMC 126289. PMID 12234920. 
  15. ^ a b Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C et al. (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. PMID 9990509. 
  16. ^ 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. PMID 18498246. 
  17. ^ Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M (February 1996). "Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5". J. Biol. Chem. 271 (5): 2795–800. doi:10.1074/jbc.271.5.2795. PMID 8576257. 
  18. ^ Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM et al. (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. PMID 10558980. 
  19. ^ Pringa E, Martinez-Noel G, Muller U, Harbers K (June 2001). "Interaction of the ring finger-related U-box motif of a nuclear dot protein with ubiquitin-conjugating enzymes". J. Biol. Chem. 276 (22): 19617–23. doi:10.1074/jbc.M100192200. PMID 11274149. 

Further reading[edit]