Biology:Ceramide synthase 2
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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.[1]
CerS2 was first identified in 2001.[2] It contains the conserved TLC domain and Hox-like domain common to almost all CerS.[3]
Distribution
CerS2 mRNA (TRH3) has been found in most tissues and it is strongly expressed in liver, intestine and brain.[4] CerS2 is much more widely distributed than Ceramide synthase 1 (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.[3][5]
Function
Expression of CerS2 is transiently increased during periods of active myelination, suggesting that it is important for the synthesis of myelin sphingolipids.[5] The lack of CerS2, as shown in knockout mice, induces the autophagy and activation of the unfolded protein response (UPR).[3] These mice showed no decrease in overall ceramide level, but levels of sphinganine were elevated. They also developed severe liver disease, but there was no observable change in the kidneys.[6]
The CerS2 gene is compact in size and is located in a chromosomal region that is replicated early in the cell cycle.[3] CerS2 activity is regulated by sphingosine-1-phosphate (S1P) via two sphingosine-1-phosphate receptor-like residues on CerS2 that operate independently.[3]
Pathological significance
CerS2 levels are significantly elevated in breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (CerS6).[3]
CerS2 was also implicated in the control of body weight. The administration of leptin to rats induced a decrease in CerS2 was observed in white adipose tissue.[3]
References
- ↑ "Ceramide Synthases: Roles in Cell Physiology and Signaling". Sphingolipids as Signaling and Regulatory Molecules. Advances in Experimental Medicine and Biology. 688. 2010. pp. 60–71. doi:10.1007/978-1-4419-6741-1_4. ISBN 978-1-4419-6740-4.
- ↑ "Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1". Genomics 77 (1–2): 58–64. September 2001. doi:10.1006/geno.2001.6614. PMID 11543633.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Mammalian ceramide synthases". IUBMB Life 62 (5): 347–56. May 2010. doi:10.1002/iub.319. PMID 20222015.
- ↑ "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". J Biol Chem 278 (44): 43452–9. Oct 2003. doi:10.1074/jbc.M307104200. PMID 12912983.
- ↑ 5.0 5.1 "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochemistry and Cell Biology 129 (2): 233–41. February 2008. doi:10.1007/s00418-007-0344-0. PMID 17901973.
- ↑ "A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy". J. Biol. Chem. 285 (14): 10911–23. April 2010. doi:10.1074/jbc.M109.077610. PMID 20110366.
Further reading
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach". Mol. Cell. Proteomics 5 (2): 226–33. 2006. doi:10.1074/mcp.M500324-MCP200. PMID 16263699.
- "Transcriptome analysis of human gastric cancer". Mamm. Genome 16 (12): 942–54. 2006. doi:10.1007/s00335-005-0075-2. PMID 16341674.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
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