StAR-related lipid transfer protein 4 (STARD4) is a soluble protein involved in

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membr ...

transport. It can transfer up to 7

sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the g ...

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 The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

. 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 Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the ''SREBF1'' gene. This gene is located within the Smith–Magenis s ...

or SREBP2, 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 (START) domain. It also lends its name to the subgroup of START domain proteins it is part of, StarD4. This subfamily includes

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 (START) domain. It is also part of the StarD4 sub ...

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

References

{{reflist Genes on human chromosome 5 Water-soluble transporters