protein modification by small protein conjugation

Definition

Target type: biologicalprocess

A protein modification process in which one or more groups of a small protein, such as ubiquitin or a ubiquitin-like protein, are covalently attached to a target protein. [GOC:mah]

Protein modification by small protein conjugation is a fundamental process in cellular biology, involving the covalent attachment of small protein tags to target proteins. These tags can be diverse, including ubiquitin, SUMO, NEDD8, and ISG15, each with distinct functions and regulatory roles. The process typically involves a multi-step cascade:

1. **Activation:** The small protein tag is activated through ATP-dependent ligation by an E1 enzyme, forming a thioester intermediate.
2. **Conjugation:** The activated tag is transferred to a cysteine residue on an E2 enzyme, a ubiquitin conjugating enzyme.
3. **Ligation:** The E2 enzyme interacts with an E3 ligase, a specific protein that recognizes the target protein and facilitates the transfer of the tag from E2 to the target. This interaction often involves a specific lysine residue on the target protein.

The addition of a small protein tag can dramatically alter the properties and fate of the target protein. These effects can include:

* **Altering protein stability:** Conjugation can increase or decrease protein stability, influencing its half-life and degradation.
* **Modifying protein localization:** Tags can act as signals to redirect proteins to specific cellular compartments, such as the nucleus, cytoplasm, or organelles.
* **Modulating protein activity:** Conjugation can activate or inhibit protein function, influencing its catalytic activity, interaction with other proteins, or ability to bind DNA.
* **Signaling:** Tags can serve as signals to initiate downstream signaling cascades, leading to changes in gene expression or other cellular processes.

Small protein conjugation is a tightly regulated process, with specific E3 ligases recognizing and targeting particular substrates. Dysregulation of this process is implicated in various diseases, including cancer, neurodegenerative disorders, and immune system dysfunction. Understanding the molecular mechanisms of protein conjugation is crucial for developing therapeutic strategies to modulate these processes.'
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Proteins (1)

Compounds (1)