LUBAC complex

Definition

Target type: cellularcomponent

A ubiquitin ligase complex that catalyzes linear head-to-tail polyubiquitin conjugation on its targets. In human the complex consists of RBCK1, RNF31 and SHARPIN, and has an MW of approximately 600 kDa, suggesting a heteromultimeric assembly of its subunits. LUBAC stands for Linear Ubiquitin Chain Assembly Complex. [GOC:sp, PMID:17006537, PMID:19136968, PMID:21455180]

The LUBAC complex, also known as linear ubiquitin chain assembly complex, is a multi-protein complex that plays a crucial role in the regulation of various cellular processes, including NF-κB signaling, immune responses, and cell death. The complex consists of three core subunits: HOIP (HOIL-1-interacting protein), HOIL-1 (Heme oxygenase-1-interacting protein), and SHARPIN (SHANK-associated RH domain-interacting protein). Each subunit contributes to the complex's structure and function.

HOIP is the catalytic subunit responsible for assembling linear ubiquitin chains. It contains a RING domain, which is essential for its E3 ligase activity. HOIL-1 is a scaffolding protein that binds to HOIP and provides a platform for the recruitment of other subunits. It also contains a C-terminal ubiquitin-like domain that interacts with SHARPIN.

SHARPIN is a regulatory subunit that regulates the activity of the complex. It contains an N-terminal RH domain that interacts with HOIL-1 and a C-terminal domain that interacts with various downstream signaling molecules. The SHARPIN domain is responsible for mediating the interaction of LUBAC with other proteins, including the adaptor protein TRAF6, which is crucial for the activation of NF-κB signaling.

The LUBAC complex is located in the cytoplasm and is recruited to specific signaling pathways by various protein interactions. For example, the complex can be recruited to the TNF receptor complex via its interaction with TRAF6. Once at the signaling site, LUBAC assembles linear ubiquitin chains on target proteins, which can then activate downstream signaling cascades.

In addition to NF-κB signaling, LUBAC is involved in other cellular processes, including:

* **Immune responses:** LUBAC is involved in the regulation of innate and adaptive immune responses. It plays a role in the activation of immune cells, such as macrophages and lymphocytes, and in the production of inflammatory cytokines.
* **Cell death:** LUBAC is involved in both apoptosis and necroptosis. It can promote cell survival by inhibiting apoptosis and promoting necroptosis.

The LUBAC complex is a crucial regulator of various cellular processes and is a promising target for the development of new therapies for diseases related to inflammation, immunity, and cancer. '
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Proteins (3)

Compounds (1)