The epididymal secretory protein E1, also known as NPC2 (Niemann-Pick intracellular cholesterol transporter 2), is one of two main lysosomal transport proteins that assist in the regulation of cellular cholesterol by exportation of LDL-derived

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 ...

from

lysosomes A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

. Lysosomes have digestive enzymes that allow it to break down LDL particles to LDL-derived cholesterol once the LDL particle is engulfed into the cell via receptor mediated endocytosis. NPC2 works cooperatively with the

NPC1 Niemann-Pick disease, type C1 (NPC1) is a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the ''NPC1'' gene (chromosome location 18q11). Function ''NPC1'' was identified as ...

protein to facilitate the exportation of LDL-derived cholesterol out of the lysosome to regulate the concentrations of lipids and cholesterol in the body. Epididymal secretory protein E1 is a protein associated with Niemann-Pick disease, type C, which is one of the 3 types of the Niemann-Pick diseases (Type A, B, and C). This disease can lead to an over accumulation of

and

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 different types of tissues, including the brain. It is caused by a mutation in the ''NPC2'' gene that impairs the body's ability to transport

intracellularly.

Structure

The epididymal secretory protein E1 is a small soluble glycoprotein consisting of 132 amino acids that is found in a large variety of cells.

Function

Lysosomal secretion of cholesterol is one part of the regulation of cholesterol in the body. LDL particles are low density lipoproteins that carry cholesterol to cells. LDL particles are engulfed into cells by

receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This ...

. Once the LDL is engulfed this results in the budding of the receptors to disassemble from the LDL vesicle and move back up to the outer membrane of the cell. This is due to the pH on the outside of the cell being less acidic than the inside of the cell. After this budding process the

lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

s fuse with LDL particles. Lysosomes break down the

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

into cholesterol and other lipids (fatty acids), hence LDL-derived

. The epididymal secretory protein E1 (NPC2) is produced via transcription of the ''NPC2'' gene and recruits and transfers the LDL-derived cholesterol to the sterol-binding pocket in the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

domain of the NPC1 protein to be transferred from the lysosome lumen and excreted from the lysosome

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

Clinical significance

Since the epididymal secretory protein E1 plays a role in the intracellular transport of cholesterol, a mutation in the gene that produces it (''NPC2'' gene) can cause serious issues that lead to Niemann-Pick disease, type C. Niemann-Pick disease, type C is a rare disorder that results in the over accumulation of lipids and cholesterol in different types of tissues in the body due to this protein being ubiquitous. Symptoms vary per individual and can be fatal at birth or go undiagnosed up until adulthood.

References

External links

* {{Protein-stub

Structure

Function

Clinical significance

See also

References

Further reading

External links