SREBP-SCAP-Insig complex

Definition

Target type: cellularcomponent

A protein complex formed by the association of sterol regulatory element binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), and an Insig protein (Insig-1 or Insig-2) in the ER membrane. [PMID:12923525]

The SREBP-SCAP-Insig complex is a crucial regulatory unit involved in cholesterol homeostasis. This complex resides within the endoplasmic reticulum (ER) membrane and is dynamically assembled and disassembled depending on cellular cholesterol levels.

**SREBP (Sterol Regulatory Element Binding Protein)**: A transcription factor responsible for upregulating genes involved in cholesterol synthesis and uptake.

**SCAP (SREBP Cleavage Activating Protein)**: A chaperone protein that escorts SREBP to the Golgi apparatus for processing.

**Insig (Insulin-induced Gene)**: A transmembrane protein that acts as a sensor for cholesterol levels within the ER membrane.

**Detailed Cellular Components:**

* **ER Membrane:** The complex is anchored to the ER membrane through the transmembrane domains of both SREBP and Insig.
* **ER Lumen:** The lumenal domain of Insig directly interacts with the sterol-sensing domain of SCAP. When cholesterol levels are high, Insig binds to SCAP, preventing its movement to the Golgi apparatus.
* **Golgi Apparatus:** When cholesterol levels are low, Insig dissociates from SCAP, allowing the complex to move to the Golgi apparatus.
* **Golgi Membrane:** Within the Golgi, SREBP undergoes proteolytic cleavage, releasing the transcriptionally active N-terminal fragment (SREBP-N).
* **Nucleus:** SREBP-N translocates to the nucleus and binds to sterol regulatory elements (SREs) in the promoter regions of target genes, stimulating their transcription.

The dynamic interplay between these components allows for precise control of cholesterol synthesis and uptake, ensuring cellular cholesterol homeostasis.
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Proteins (1)

Compounds (2)