Ceramide synthase 2

Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an is_associated_with::enzyme that in humans is encoded by the CERS2 is_associated_with::gene.

Ceramide synthase 2 is a is_associated_with::ceramide synthase that catalyses the synthesis of very long acyl chain is_associated_with::ceramides, including C20 and C26 ceramides. It is the most ubiquitously expressed of all CerS and has the broadest distribution in the human body.

CerS2 was first identified in 2001. It contains the conserved is_associated_with::TLC domain and Hox-like domain common to almost all CerS.

Distribution
CerS2 is much more widely distributed than is_associated_with::Ceramide synthase 1 (CerS1) and is found in at least 12 tissues in the human body, with high expression in the is_associated_with::kidney and is_associated_with::liver, and moderate expression in the is_associated_with::brain and other organs. In the mouse brain, CerS2 is mainly expressed is_associated_with::white matter tracts, specifically in is_associated_with::oligodendrocytes and is_associated_with::Schwann cells.

Function
Expression of CerS2 is transiently increased during periods of active myelination, suggesting that it is important for the synthesis of is_associated_with::myelin sphingolipids. The lack of CerS2, as shown in is_associated_with::knockout mice, induces the is_associated_with::autophagy and activation of the is_associated_with::unfolded protein response (UPR). These mice showed no decrease in overall ceramide level, but levels of is_associated_with::sphinganine were elevated. They also developed severe liver disease, but there was no observable change in the kidneys.

The CerS2 gene is compact in size and is located in a chromosomal region that is replicated early in the is_associated_with::cell cycle. CerS2 activity is regulated by is_associated_with::sphingosine-1-phosphate (S1P) via two is_associated_with::sphingosine-1-phosphate receptor-like residues on CerS2 that operate independently.

Pathological Significance
CerS2 levels are significantly elevated in is_associated_with::breast cancer tissue compared to normal tissue, along with increased levels of is_associated_with::ceramide synthase 6 (CerS6).

CerS2 was also implicated in the control of body weight. The administration of is_associated_with::leptin to rats induced a decrease in CerS2 was observed in is_associated_with::white adipose tissue.