GRAM domain containing 1A also known as Aster-A is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is encoded by the GRAMD1A

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. It contains a

transmembrane region Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral me ...

, a

GRAM domain The GRAM domain is found in glucosyltransferases, myotubularins and other membrane-associated proteins. The structure of the GRAM domain is similar to that found in PH domains. Proteins containing GRAM domains are found in all eukaryotes and b ...

and a VASt domain that can bind

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

. GRAMD1A has four

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

GRAMD1B GRAM domain containing 1B, also known as GRAMD1B, Aster-B and KIAA1201, is a cholesterol transport protein that is encoded by the ''GRAMD1B'' gene. It contains a Transmembrane protein, transmembrane region and two Protein domain, domains of know ...

and GRAMD1C and two without VASt domains, GRAMD2A and GRAMD2B. These proteins are mammalian representatives of the

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

transfer proteins anchored at a membrane contact site (LAM) family. The protein is expressed ubiquitously with higher levels in the central nervous system.

Function

GRAMD1A localizes to the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. Its GRAM domain tethers it to the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

where it can bind phosphatidylinositol phosphate in areas enriched for it. When the

contains high levels of cholesterol, GRAMD1a like GRAMD1b and GRAMD1c moves to sites of contact between the plasma membrane and the endoplasmic reticulum. The VASt domain of GRAMD1A then binds cholesterol and cholesterol is moved from the plasma membrane to the endoplasmic reticulum. The VASt domain is responsible for binding cholesterol while the GRAM domain determines the location of the protein through sensing of cholesterol and binding partially negatively charged

lipids Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and others. The fu ...

in the plasma membrane, especially

phosphatidylserine Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via a ...

. GRAMD1A also is necessary for

autophagosome An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, i ...

biogenesis Spontaneous generation is a Superseded scientific theories, superseded scientific theory that held that living creatures could arise from abiotic component, non-living matter and that such processes were commonplace and regular. It was Hypoth ...

Function

References

Further reading