GRAMD1C
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GRAM domain containing 1C also known as Aster-C is a
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 ...
transport
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 GRAMD1C
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. It is anchored 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 ...
through its transmembrane domain. GRAMD1C 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 GRAMD1A and two without VASt domains, GRAMD2A and GRAMD2B.
Homologs Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same loci, where they provide points along each chromosome th ...
of GramD proteins (Lam/Ltc proteins) are found in yeast. The protein is expressed in the liver and testes.


Function

When 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 ...
contains high levels of cholesterol, GRAMD1c as well as GRAMD1a and GRAMD1b move 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 a form of
non-alcoholic fatty liver disease An alcohol-free or non-alcoholic drink, also known as a temperance drink, is a version of an alcoholic drink made without alcohol, or with the alcohol removed or reduced to almost zero. These may take the form of a non-alcoholic mixed drink or n ...
, non-alcoholic steatohepatitis (NASH) in mice. 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 ...
.


References

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