Ceramide synthase 3

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

CERS3
Identifiers
AliasesCERS3, ARCI9, LASS3, ceramide synthase 3
External IDsOMIM: 615276 MGI: 2681008 HomoloGene: 18719 GeneCards: CERS3
Orthologs
SpeciesHumanMouse
Entrez

204219

545975

Ensembl

ENSG00000154227

ENSMUSG00000030510

UniProt

Q8IU89

Q1A3B0

RefSeq (mRNA)

NM_001290341
NM_001290342
NM_001290343
NM_178842
NM_001378789

NM_001164201

RefSeq (protein)

NP_001277270
NP_001277271
NP_001277272
NP_849164
NP_001365718

NP_001157673

Location (UCSC)Chr 15: 100.4 – 100.54 MbChr 7: 66.39 – 66.47 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

CerS3 synthesizes C24-ceramides and ceramides with longer acyl chains, and is found mainly in skin and testis.[5] 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.[6] It is found in large quantities in keratinocytes, and this increases during keratinocyte differentiation.[7]

In the testes, CerS3 is involved in sperm formation and androgen production.[5] 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.[8]

Tissue and cellular distribution

CerS3 (T3l) mRNA is strongly expressed in skin, and was also found in brain, lung and kidney.[9] CerS3 is mainly found in the skin and testes. CerS3 is not detectable in the brain or the sciatic nerve.[10] Like other ceramide synthases, CerS3 is found in the endoplasmic reticulum within the cell.[11]

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.[11] CerS3 is the only ceramide synthase for which splice variants have not been reported.[12]

References
  1. GRCh38: Ensembl release 89: ENSG00000154227 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030510 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Mizutani Y, Kihara A, Igarashi Y (2006). "LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity". Biochem. J. 398 (3): 531–8. doi:10.1042/BJ20060379. PMC 1559458. PMID 16753040.
  6. Han X, Gross RW (2005). "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. doi:10.1002/mas.20023. PMID 15389848.
  7. Mizutani Y, Kihara A, Chiba H, Tojo H, Igarashi Y (2008). "2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length". J. Lipid Res. 49 (11): 2356–64. doi:10.1194/jlr.M800158-JLR200. PMID 18541923.
  8. Rabionet M, van der Spoel AC, Chuang CC, von Tümpling-Radosta B, Litjens M, Bouwmeester D, Hellbusch CC, Körner C, Wiegandt H, Gorgas K, Platt FM, Gröne HJ, Sandhoff R (2008). "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. doi:10.1074/jbc.M800870200. PMC 2442322. PMID 18308723.
  9. Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH (Oct 2003). "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. doi:10.1074/jbc.M307104200. PMID 12912983.
  10. Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M (2008). "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochem. Cell Biol. 129 (2): 233–41. doi:10.1007/s00418-007-0344-0. PMID 17901973. S2CID 2595275.
  11. Mullen TD, Hannun YA, Obeid LM (2012). "Ceramide synthases at the centre of sphingolipid metabolism and biology". Biochem. J. 441 (3): 789–802. doi:10.1042/BJ20111626. PMC 3689921. PMID 22248339.
  12. Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
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