Gram domain containing 1a

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GRAMD1A (Gram domain containing 1A), also known as Aster-A, is a protein that helps manage cholesterol in cell membranes. It has three main parts: a transmembrane region, a GRAM domain that helps it attach to membranes, and a VASt domain that binds cholesterol.

Location and relatives
- In humans, the GRAMD1A gene is on chromosome 19q13.11.
- It has related proteins: GRAMD1B and GRAMD1C (which also have VASt domains) and two forms, GRAMD2A and GRAMD2B, that lack VASt.
- The mouse version is on chromosome 7.

Structure and how it works
- The GRAM domain tethers the protein to the plasma membrane and can bind phosphatidylinositol phosphates and other negatively charged lipids like phosphatidylserine.
- The VASt domain binds cholesterol.
- When the plasma membrane has high cholesterol, GRAMD1A (and its relatives) moves to sites where the endoplasmic reticulum (ER) and plasma membrane touch. At these ER–PM contact sites, the VASt domain captures cholesterol and helps move it from the plasma membrane to the ER.
- This protein also plays a role in autophagy, the process cells use to recycle parts of themselves.

Expression and importance
- GRAMD1A is expressed in many tissues, with higher levels in the central nervous system.

In short, GRAMD1A is a cholesterol-sensing protein that sits at ER–plasma membrane contact sites, helps transport cholesterol to the ER, and participates in autophagy.