GRAMD1C
Description
The GRAMD1C (GRAM domain containing 1C) is a protein-coding gene located on chromosome 3.
GRAMD1C, also known as Aster-C, is a cholesterol transport protein encoded by the GRAMD1C gene. It contains a transmembrane region, a GRAM domain, and a VASt domain, anchoring it to the endoplasmic reticulum through its transmembrane domain. GRAMD1C has four paralogs: GRAMD1B and GRAMD1A, both containing VASt domains, and GRAMD2A and GRAMD2B, lacking VASt domains. Homologs of GramD proteins (Lam/Ltc proteins) are found in yeast. The protein is expressed in the liver and testes. When the plasma membrane contains high levels of cholesterol, GRAMD1C, along with GRAMD1A and GRAMD1B, relocate to sites of contact between the plasma membrane and the endoplasmic reticulum. GRAMD1 proteins then facilitate the transport of cholesterol into the endoplasmic reticulum. Reduction of GRAMD1B and GRAMD1C suppresses the onset of non-alcoholic steatohepatitis (NASH) in mice. The VASt domain is responsible for binding cholesterol, while the GRAM domain determines the protein's location by sensing cholesterol and binding partially negatively charged lipids in the plasma membrane, especially phosphatidylserine.
GRAMD1C is a cholesterol transporter protein that facilitates the movement of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) without the use of vesicles. It achieves this by acting as a molecular bridge, utilizing its unique domains to bind both cholesterol and the PM. GRAMD1C plays a vital role in maintaining cholesterol balance within the cell. Notably, its localization within the cell is dynamically regulated by the levels of cholesterol in the PM. When cholesterol levels are low, GRAMD1C resides in the ER membrane. However, in response to elevated cholesterol levels in the PM, GRAMD1C is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS). This recruitment is driven by its GRAM domain, which senses and binds to partially negatively charged lipids in the PM, particularly phosphatidylserine. Once at the EPCS, GRAMD1C's sterol-binding VASt/ASTER domain binds to cholesterol within the PM, facilitating the transfer of cholesterol from the PM to the ER.
GRAMD1C is also known as -.
Associated Diseases
- hypertriglyceridemia 2
- hemoglobin D disease
- cholesterol-ester transfer protein deficiency
- isolated asymptomatic elevation of creatine phosphokinase
- pentosuria
- Imerslund-Grasbeck syndrome type 2
- hypoalphalipoproteinemia, primary, 1
- dominant beta-thalassemia
- hemoglobin E disease
- homozygous familial hypercholesterolemia
- delta-beta-thalassemia
- alpha-thalassemia-myelodysplastic syndrome
- hemoglobin C-beta-thalassemia syndrome
- hemoglobin E-beta-thalassemia syndrome
