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Literature summary extracted from

  • Ullah, K.; Zubia, E.; Narayan, M.; Yang, J.; Xu, G.
    Diverse roles of the E2/E3 hybrid enzyme UBE2O in the regulation of protein ubiquitination, cellular functions, and disease onset (2019), FEBS J., 286, 2018-2034 .
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.2.24 diagnostics high expression of UBE2O is associated with low survival rate of gastric, lung, breast, and prostate cancer patients Homo sapiens
2.3.2.24 drug development E2 ubiquitin-conjugating enzymes might be potential drug targets, potential strategies for drug discovery targeting UBE2O, overview Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.2.24 gene UBE2O, cloned from liver, DNA and amino acid sequence determination and comparisons Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.24 cytosol
-
 Homo sapiens 5829
-
2.3.2.24 additional information even though UBE2O has two nuclear localization sequences (NLSs), only a small fraction of this protein is translocated to the nucleus, which suggests that its localization may be governed by specific signaling pathways, post-translational modifications, or protein-protein interactions. In fact, UBE2O contains several potential phosphorylation sites and their phosphorylation may regulate UBE2O localization and its physiological roles Homo sapiens
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-
2.3.2.24 nucleus
-
 Homo sapiens 5634
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.3.2.24 141000
-
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine Homo sapiens
-
 [E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [AMPKalpha2]-L-lysine48 Homo sapiens
-
 [E1 ubiquitin-activating enzyme]-L-cysteine + [AMPKalpha2]-N6-monoubiquitinyl-L-lysine48
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BAP1]-L-lysine Homo sapiens UBE2O promotes multi-monoubiquitination on BAP1. The ubiquitination of BAP1 requires both the N-terminal CR1-CR2 domain and the C-terminal UBC domain of UBE2O. The absence of either domain completely abolishes BAP1 ubiquitination [E1 ubiquitin-activating enzyme]-L-cysteine + [BAP1]-N6-monoubiquitinyl-L-lysine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.24 Homo sapiens Q9C0C9
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.3.2.24 phosphoprotein UBE2O contains several potential phosphorylation sites and their phosphorylation may regulate UBE2O localization and its physiological roles Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.24 carcinoma cell UBE2O expression in cell lines and cancers, and UBE2O expression and mutation in cancers, detailed overview Homo sapiens
-
2.3.2.24 heart
-
 Homo sapiens
-
2.3.2.24 liver
-
 Homo sapiens
-
2.3.2.24 additional information UBE2O mRNA is expressed in all organs but preferentially in heart and skeletal muscle Homo sapiens
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2.3.2.24 skeletal muscle
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.24 additional information UBE2O is an E2/E3 hybrid enzyme and exhibits both the E2 and E3 activities. UBE2O performs monoubiquitination, multi-monoubiquitination, and polyubiquitination of different substrates, mechanisms, overview. A consensus sequence analysis of the UBE2O-mediated ubiquitination sites discovers the VLI patch-containing bipartite NLS as the putative UBE2O recognition sequence Homo sapiens ?
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-
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine
-
 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [AMPKalpha2]-L-lysine48
-
 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [AMPKalpha2]-N6-monoubiquitinyl-L-lysine48
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [AMPKalpha2]-L-lysine48 polyubiquitination of AMPKalpha2 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [AMPKalpha2 ]-N6-monoubiquitinyl-L-lysine48
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BAP1]-L-lysine UBE2O promotes multi-monoubiquitination on BAP1. The ubiquitination of BAP1 requires both the N-terminal CR1-CR2 domain and the C-terminal UBC domain of UBE2O. The absence of either domain completely abolishes BAP1 ubiquitination Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [BAP1]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [BMAL1]-L-lysine polyubiquitination of BMAL1 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [BMAL1]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [c-Maf]-L-lysine polyubiquitination of o-Maf Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor c-Maf]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [MLL protein]-L-lysine polyubiquitination of protein MLL Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [MLL protein]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [SMAD6]-L-lysine monoubiquitination of SMAD6 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [SMAD6]-N6-monoubiquitinyl-L-lysine
-
 ?
2.3.2.24 [E1 ubiquitin-activating enzyme]-S-ubiquitinyl-L-cysteine + [TRAF6]-L-lysine63 polyubiquitination of TRAF6 K63 Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + [TRAF6]-N6-monoubiquitinyl-L-lysine63
-
 ?

Subunits

EC Number Subunits Comment Organism
2.3.2.24 More the major functional domains of UBE2O include three conserved regions (CR1, CR2, and CR3), a coiled-coil (CC) domain, a UBC domain, and two putative nuclear localization sequences (NLSs). CR1 and CR2 act as substrate-binding domains, although their binding capability is variable, whereas the UBC domain can interact with multiple E3 ligases Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.3.2.24 E2/E3 hybrid enzyme
-
 Homo sapiens
2.3.2.24 UBE2O
-
 Homo sapiens
2.3.2.24 ubiquitin-conjugating enzyme E2 O
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.2.24 evolution ubiquitin-conjugating enzyme E2 O (UBE2O) is a member of the E2 family of the ubiquitin-proteasome system (UPS). Unlike most members of this family which are about 20 to 25 kDa in molecular weight, UBE2O is unusually large, with a molecular weight of 141 kDa Homo sapiens
2.3.2.24 malfunction inhibition of UBE2O or depletion of UBE2O leads to the reduced growth of breast and prostate cancer cells, but inactivation of AMPKalpha2 abrogates the beneficial effect caused by the UBE2O loss Homo sapiens
2.3.2.24 metabolism the ubiquitin-proteasome system is an important regulatory machinery involved in proteostasis and cellular signaling. Proteins are ubiquitinated via the concerted action of E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin ligases. UBE2O is an E2/E3 hybrid enzyme and exhibits both the E2 and E3 activities. Role of UBE2O in the development of hematological disorders and cancers, overview Homo sapiens
2.3.2.24 additional information homology modeling of UBE2O, using the recombinant enzyme and structure of the MZM-REP domains of Mind bomb 1 (Mib1, PDB ID 4XI6) and the UBC domain of baculoviral IAP repeat-containing protein 6 (BIRC6, PDB ID 3CEG), respectively, overview. UBE2O also displays nonenzymatic functions, and as a protein-interacting partner it can block protein ubiquitination. The N-terminus of UBE2O interacts efficiently with the TRAF domain in TNF receptor-associated factor 6 (TRAF6), prevents its K63-linked polyubiquitination, competes with myeloid differentiation primary response protein MyD88 for TRAF6, and thus suppresses the activation of NF-kappaB induced by lipopolysaccharide and interleukin-1beta. Loss of the UBC domain in UBE2O does not affect this regulation, indicating that its nonenzymatic function prevents TRAF6 ubiquitination Homo sapiens
2.3.2.24 physiological function the ubiquitin-conjugating enzyme E2 O (UBE2O) is an E3-independent E2 (i.e. an E2/E3 hybrid enzyme), can directly mediate the ubiquitination of many substrates, e.g. 5'-AMP-activated protein kinase catalytic subunit alpha2 (AMPKalpha2), tumor suppressor ubiquitin carboxyl-terminal hydrolase BAP1, mixed-lineage leukemia (MLL) protein, SMAD family member 6 (SMAD6), transcription factor c-Maf and aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1), and free ribosomal proteins, which are ubiquitinated in distinct ways, thereby associating UBE2O with a variety of biological functions. The presence of multifunctional domains in UBE2O suggests that it might act on a broad spectrum of targets and execute diverse biological functions. Although UBE2O is first identified as an E2 enzyme, it is subsequently discovered that it also functions as an E2/E3 hybrid enzyme. UBE2O also functions as an E3 enzyme which is fused to an E2 enzyme and carries out the E3-independent ubiquitination. UBE2O may involve an intramolecular thiol relay mechanism. UBE2O mediates monoubiquitination, multi-monoubiquitination, and polyubiquitination of different substrates and thereby performs its diverse functions. UBE2O specifically targets AMPKalpha2 but not AMPKalpha1 for the formation of K48-linked polyubiquitin chains and for its subsequent degradation by the 26S proteasome, importance of UBE2O-mediated ubiquitination of AMPKalpha2 on tumor cell growth Homo sapiens