Biology:Ceramide synthase 3

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Ceramide synthase 3 (CersS3), also known as longevity assurance homologue 3, is an enzyme that is encoded in humans by the CERS3 gene.

Function

CerS3 synthesizes C24-ceramides and ceramides with longer acyl chains, and is found mainly in skin and testis.[1] Specifically, CerS3 synthesizes ceramides containing α-hydroxy (2-hydroxy) fatty acids, which are abundant in skin tissue, where they help maintain the water permeability barrier qualities of the skin.[2] It is found in large quantities in keratinocytes, and this increases during keratinocyte differentiation.[3]

In the testes, CerS3 is involved in sperm formation and androgen production.[1] Cers3 gene expression is located within germ cells, where it is massively upregulated during juvenile testicular maturation. This upregulation is correlated with increase in levels of glycosphingolipids containing very long chain (C26-C32) polyunsaturated fatty acid (LC-PUFA), which are required for spermatogenesis.[4]

Tissue and cellular distribution

CerS3 (T3l) mRNA is strongly expressed in skin, and was also found in brain, lung and kidney.[5] CerS3 is mainly found in the skin and testes. CerS3 is not detectable in the brain or the sciatic nerve.[6] Like other ceramide synthases, CerS3 is found in the endoplasmic reticulum within the cell.[7]

Structure

CerS3 has a molecular mass of 46.2 kDa, 383 amino acids, and six transmembrane domains. Like other ceramide synthases, CerS3 contains a Hox-like domain.[7] CerS3 is the only ceramide synthase for which splice variants have not been reported.[8]

References

  1. 1.0 1.1 "LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity". Biochem. J. 398 (3): 531–8. 2006. doi:10.1042/BJ20060379. PMID 16753040. 
  2. "Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples". Mass Spectrom Rev 24 (3): 367–412. 2005. doi:10.1002/mas.20023. PMID 15389848. 
  3. "2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length". J. Lipid Res. 49 (11): 2356–64. 2008. doi:10.1194/jlr.M800158-JLR200. PMID 18541923. 
  4. "Male germ cells require polyenoic sphingolipids with complex glycosylation for completion of meiosis: a link to ceramide synthase-3". J. Biol. Chem. 283 (19): 13357–69. 2008. doi:10.1074/jbc.M800870200. PMID 18308723. 
  5. "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. 
  6. "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochem. Cell Biol. 129 (2): 233–41. 2008. doi:10.1007/s00418-007-0344-0. PMID 17901973. 
  7. 7.0 7.1 "Ceramide synthases at the centre of sphingolipid metabolism and biology". Biochem. J. 441 (3): 789–802. 2012. doi:10.1042/BJ20111626. PMID 22248339. 
  8. "Mammalian ceramide synthases". IUBMB Life 62 (5): 347–56. 2010. doi:10.1002/iub.319. PMID 20222015.