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E2 Ubiquitin/Ubl Conjugating Enzymes

E2 Ubiquitin/Ubl Conjugating Enzymes Background

About E2 Ubiquitin/Ubl Conjugating Enzymes

The ubiquitin-conjugating enzyme (E2) is the central player of the three enzymes responsible for attaching ubiquitin (Ub) to cellular proteins and consists of a ubiquitin-binding domain (UBD) and a catalytic structural domain. Its ubiquitin-binding domain can bind ubiquitin and can interact with ubiquitin-activating enzyme E1 or ubiquitin ligase E3. Its catalytic structural domain is responsible for transferring ubiquitin to target proteins. Based on the characteristics of the catalytic structural domain, E2 ubiquitin-conjugating enzymes can be divided into several families, such as UbcH, Ube2, and Ubc.In humans, about 40 E2s are involved in the transfer of Ub or Ub-like (Ubl) proteins such as SUMO and NEDD8. Although most E2s are only twice the size of Ub, this remarkable family of enzymes plays a variety of functional roles.

E2 ubiquitin-conjugating enzymes play important regulatory roles in the cell. They are involved in many cellular processes, such as protein degradation, DNA repair, cell cycle regulation, and signal transduction. By ubiquitinating target proteins, E2 ubiquitin-conjugating enzymes can regulate their stability and function within the cell. In addition, E2 ubiquitin-conjugating enzymes can transfer ubiquitin molecules to downstream E3 ubiquitin ligase or target proteins via ubiquitin ligase cascade reactions.

Mechanism of E2 Ubiquitin/Ubl Conjugating Enzymes

In the ubiquitin ligase cascade reaction, E2 ubiquitin ligase needs to interact with E1 ubiquitin-activating enzyme and E3 ubiquitin ligase to realize the process of ubiquitin transfer through a specific enzymatic mechanism:

  • First, the E1 ubiquitin-activating enzyme binds ubiquitin to ATP to form the ubiquitin-AMP intermediate and transfers it to the active site of E2 ubiquitin ligase.
  • Then, E2 ubiquitin-conjugating enzyme releases ubiquitin from the ubiquitin-AMP intermediate and binds it to E3 ubiquitin ligase.
  • Finally, E3 ubiquitin ligase transfers ubiquitin from E2 ubiquitin-conjugating enzyme to the target protein, completing the ubiquitination process.

Functions of E2 Ubiquitin/Ubl Conjugating Enzymes

E2 ubiquitin-conjugating enzymes have a variety of functional applications within the cell:

  • Protein degradation

E2 ubiquitin-conjugating enzymes act in concert with E3 ubiquitin ligases and E1 ubiquitin-activating enzymes to regulate the stability and function of target proteins by ubiquitinating them within the cell. This process labels proteins for degradation by the proteasome and maintains intracellular protein quality control.

  • DNA repair

E2 ubiquitin-conjugating enzymes are involved in the DNA repair process and maintain genome stability and integrity by regulating the level of ubiquitination of DNA repair proteins.

  • Cell cycle regulation

E2 ubiquitin-conjugating enzymes are involved in cell cycle regulation. They regulate the ubiquitination level of cell cycle-related proteins to ensure the accurate progression of cell cycle stages.

  • Signal transduction

E2 ubiquitin-conjugating enzymes are involved in the regulation of several signal transduction pathways, affecting the strength and duration of signaling by regulating the ubiquitination status of signaling molecules.

Available Resources of E2 Ubiquitin/Ubl Conjugating Enzymes

Creative BioMart is a leading biotechnology company offering high-quality products and services including E2 ubiquitin-conjugating enzyme products and services. Products include recombinant proteins, cell & tissue lysates, protein pre-coupled magnetic beads, and other products to support E2 ubiquitin-conjugating enzyme activity, regulation, and function research. We offer the following E2ubiquitin-conjugating enzyme-related products to our customers:

In addition to products and customization services, Creative BioMart offers E2 ubiquitin-conjugating enzymes-related signaling pathways, protein functions, interactions proteins, research areas, and other resources to support the study of various biological processes and pathways. Please note that the products, services, and resources offered vary with each product, and the information on the page is provided for informational purposes only, please contact us with any questions or requests.

The process of ubiquitination consists of the sequential and cooperative actions of three classes of enzymes. Fig. 1. The process of ubiquitination consists of the sequential and cooperative actions of three classes of enzymes that catalyze the attachment of the protein Ubiquitin (Ub, green spheres) to substrate proteins. (Valimberti I, et al., 2015)

References:

  1. Valimberti I, Tiberti M, Lambrughi M, et al. E2 superfamily of ubiquitin-conjugating enzymes: constitutively active or activated through phosphorylation in the catalytic cleft[J]. Scientific Reports, 2015, 5(1): 14849.
  2. Roman-Trufero M, Dillon N. The UBE2D ubiquitin-conjugating enzymes: Potential regulatory hubs in development, disease, and evolution[J]. Frontiers in Cell and Developmental Biology, 2022, 10: 1058751.
  3. Stewart M D, Ritterhoff T, Klevit R E, et al. E2 enzymes: more than just middlemen [J]. Cell research, 2016, 26(4): 423-440.
  4. van Wijk S J L, Timmers H T M. The family of ubiquitin‐conjugating enzymes (E2s): deciding between life and death of proteins[J]. The FASEB Journal, 2010, 24(4): 981-993.
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