STARD4
Encyclopedia
StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 transport. It can transfer up to 7 sterol
Sterol
Sterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol...

 molecules per minute between artificial membranes.

Function

STARD4 may regulate cholesterol levels in many cells, including in the liver. STARD4 has specifically been linked to the movement of cholesterol to the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

. The protein is associated with the endoplasmic reticulum and lipid droplets. Increases in the protein relate to cell stress.

High levels of STARD4 increases the synthesis of bile acids and cholesterol esters in liver hepatocytes. Reductions in cholesterol synthesis by cells increase STARD4 levels while StarD4 declines in mice fed a high cholesterol diet.

Increases in levels of either master gene regulator SREBP-1a or SREBP2
SREBF2
Sterol regulatory element-binding protein 2 also known as sterol regulatory element binding transcription factor 2 is a protein that in humans is encoded by the SREBF2 gene.- Function :...

, which both promote the production of proteins involved in cholesterol synthesis, increase StarD4 levels in mouse liver. Conversely, increased STARD4 increases active SREBP2 levels.

Loss of the protein in mice has little effect. Mice without functional STARD4 weigh less and females tend to have lower cholesterol profiles. The most dramatic change observed to date is a reduction in NPC-1, a protein involved in bringing cholesterol into cells.

Structure

The protein is 205 amino acids long in the human (224 in the mouse) and almost entirely consists of a StAR-related transfer
StAR-related transfer domain
START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR , a mitochondrial protein that is synthesized in steroid-producing cells. StAR and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in...

 (START) domain. It also lends its name to the subgroup of START domain proteins it is part of, StarD4. This subfamily includes STARD5
STARD5
StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene. The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer domain...

and STARD6 and is closely related to the StarD1/D3 group.
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