Recombinant Human INSIG1 protein

INSIG1 (Insulin-Induced Gene 1) is an endoplasmic reticulum (ER)-resident membrane protein that plays a critical role in regulating cellular cholesterol homeostasis. It acts as a key mediator in the sterol regulatory element-binding protein (SREBP) pathway, which controls lipid synthesis and uptake. Under low cholesterol conditions, INSIG1 interacts with SREBP cleavage-activating protein (SCAP), retaining the SREBP-SCAP complex in the ER and preventing its transport to the Golgi for proteolytic activation. When cholesterol levels rise, INSIG1 dissociates from SCAP, enabling SREBP processing and subsequent expression of cholesterol biosynthetic genes. This feedback mechanism ensures tight control of lipid metabolism.

Recombinant INSIG1 protein is engineered using expression systems (e.g., bacterial, mammalian) to produce purified, functional INSIG1 for experimental studies. Its recombinant form often includes tags (e.g., His, GST) for simplified detection and purification. Researchers utilize this tool to investigate molecular interactions within the SREBP pathway, particularly its sterol-dependent binding to SCAP or 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in cholesterol synthesis.

Studies involving recombinant INSIG1 have advanced our understanding of metabolic disorders, such as atherosclerosis and fatty liver disease, and its potential as a therapeutic target. Additionally, it aids in structural analyses (e.g., crystallography) to map binding domains critical for cholesterol sensing. The protein's role in cancer biology is also emerging, as dysregulated lipid metabolism is a hallmark of tumorigenesis. By enabling precise manipulation in vitro, recombinant INSIG1 serves as a vital resource for dissecting cholesterol regulatory networks and developing interventions for metabolic diseases.