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Literature summary for 2.3.2.23 extracted from

  • Alpi, A.F.; Chaugule, V.; Walden, H.
    Mechanism and disease association of E2-conjugating enzymes lessons from UBE2T and UBE2L3 (2016), Biochem. J., 473, 3401-3419 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine UBE2L3 might be a potential therapeutic target to treat SLE and B-cell lymphomas that are characterized by LUBAC hyperactivation and constitutive NF-kappaB signalling Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene UBE2T, genotyping Homo sapiens

Protein Variants

Protein Variants Comment Organism
A157C a naturally occuring mutation involved in the Fanconi anaemia syndrome Homo sapiens
additional information genome analysis for patient PNGS-252 revealed a maternal c.4C>G missense alteration resulting in the Gln2Glu amino acid substitution and a paternal 23 kb deletion across the UBE2T locus. The Gln2 residue in helix1 of UBE2T is not an integral part of the UBE2T-FANCL interaction surface Homo sapiens
Q2E a naturally occuring mutation involved in the Fanconi anaemia syndrome Homo sapiens
Q37R a naturally occuring mutation involved in the Fanconi anaemia syndrome Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine Homo sapiens
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[E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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?

Organism

Organism UniProt Comment Textmining
Homo sapiens P68036
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Homo sapiens Q9NPD8
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine
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Homo sapiens [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine
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?

Synonyms

Synonyms Comment Organism
E2-conjugating enzyme
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Homo sapiens
FANCT
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Homo sapiens
UbcH7
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Homo sapiens
UBE2L3
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Homo sapiens
UBE2T
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Homo sapiens

General Information

General Information Comment Organism
evolution enzyme UBE2L3 belongs to the E2 family. Humans have around 35 ubiquitin E2 family members, all sharing a core ubiquitin conjugation (UBC) domain that spans roughly 150 residues. E2s are classified by their UBC domain extensions, class I E2s have only the core domain, classes II and III have N- or C-terminal extensions respectively, and class IV are extended at both ends Homo sapiens
evolution enzyme UBE2T belongs to the E2 family. Humans have around 35 ubiquitin E2 family members, all sharing a core ubiquitin conjugation (UBC) domain that spans roughly 150 residues. E2s are classified by their UBC domain extensions, class I E2s have only the core domain, classes II and III have N- or C-terminal extensions respectively, and class IV are extended at both ends Homo sapiens
malfunction mutation in UBE2T are involved in the Fanconi anaemia pathway. UBE2T is the E2 enzyme in the Fanconi anaemia pathway, the Fanconi anaemia ubiquitin signalling module. Analysis of E2 function in the Fanconi anaemia syndrome (FA) disease, patient phenotypes, detailed overview Homo sapiens
metabolism the enzyme is involved in the ubiquitin pathway. The E1 mediates ubiquitin activation in an energy-consuming step. The ubiquitin thioester is then transferred onto a catalytic cysteine of the E2 enzyme. RING-type E3s form a non-covalent complex with the E2-Ub thioester intermediate or, alternatively, ubiquitin is transferred to catalytic sites of HECT and RBR-type E3 ligases. The E3 enzymes ultimately catalyze ubiquitination of a substrate lysine. Ubiquitin signals can also be extended to form polyubiquitin chains Homo sapiens
additional information structure-function overview of the E2 fold Homo sapiens
physiological function ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Function of UBE2L3 with HOIL-1L-interacting protein (HOIP) in cancer. HOIL-1L is the haem-oxidized IRP2 ubiquitin ligase-1. Functional association of UBE2L3 with Parkinson's disease (PD). Parkin E3 ligase activity is auto-inhibited by the N-terminal UBL domain, which obscures the catalytic interaction between Parkin and the ubiquitin-loaded E2. Parkin apparently employs different E2 enzymes to generate distinct ubiquitin chain signals that mediate efficient mitophagy. The apparent redundant functions of UBE2L3 with other E2s may explain the current lack of any genetic association of UBE2L3 gene alterations with PD Homo sapiens
physiological function ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. UBE2T has potential oncogenic and tumour suppressor function in carcinogenesis Homo sapiens