Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an
enzyme that in humans is encoded by the CERS2
gene.
Ceramide synthase 2 is a
ceramide synthase that
catalyses the synthesis of very long acyl chain
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
TLC domain
TLC may refer to:
Arts and entertainment Television
* ''TLC'' (TV series), a 2002 British situational comedy television series that aired on BBC2
* TLC (TV network), formerly the Learning Channel, an American cable TV network
** TLC (Asia), an As ...
and
Hox-like domain common to almost all CerS.
Distribution
CerS2 mRNA (TRH3) has been found in most tissues and it is strongly expressed in liver, intestine and brain.
CerS2 is much more widely distributed than
Ceramide synthase 1
Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an enzyme that in humans is encoded by the ''CERS1'' gene.
Function
This gene encodes a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfami ...
(CerS1) and is found in at least 12 tissues in the human body, with high expression in the
kidney and
liver, and moderate expression in the
brain and other organs. In the
mouse brain, CerS2 is mainly expressed
white matter tracts, specifically in
oligodendrocytes and
Schwann cells.
Function
Expression of CerS2 is transiently increased during periods of active myelination, suggesting that it is important for the synthesis of
myelin sphingolipids.
The lack of CerS2, as shown in
knockout mice
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
, induces the
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
and activation of the
unfolded protein response (UPR).
These mice showed no decrease in overall ceramide level, but levels of
sphinganine
Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an in ...
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
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
region that is
replicated early in the
cell cycle.
CerS2 activity is regulated by
sphingosine-1-phosphate (S1P) via two
sphingosine-1-phosphate receptor
The sphingosine-1-phosphate receptors are a class of G protein-coupled receptors that are targets of the lipid signalling molecule Sphingosine-1-phosphate (S1P). They are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5.
Discovery ...
-like residues on CerS2 that operate independently.
Pathological significance
CerS2 levels are significantly elevated in
breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (
CerS6).
CerS2 was also implicated in the control of body weight. The administration of
leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...
to rats induced a decrease in CerS2 was observed in
white adipose tissue.
References
Further reading
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Integral membrane proteins