Ceramide synthase 3

CERS3
Identifiers
Aliases	CERS3, ARCI9, LASS3, ceramide synthase 3
External IDs	OMIM: 615276; MGI: 2681008; GeneCards: CERS3
Enzyme activity
Gene location (Human)
Chr.	Chromosome 15 (human)
End	100,544,995 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	66,473,439 bp
RNA expression pattern
	Top expressed in
	skin of abdomen; ; skin of leg; ; gums; ; oral cavity; ; gingival epithelium; ; vulva; ; skin of thigh; ; buccal mucosa cell; ; human penis; ; vagina;
	Top expressed in
	spermatocyte; ; transitional epithelium of urinary bladder; ; esophagus; ; seminiferous tubule; ; spermatid; ; conjunctival fornix; ; skin of back; ; skin of abdomen; ; skin of external ear; ; lip;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity; DNA binding; sphingosine N-acyltransferase activity; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	integral component of membrane; nuclear membrane; endoplasmic reticulum membrane; nucleus; membrane; endoplasmic reticulum;
Biological process	ceramide biosynthetic process; sphingolipid biosynthetic process; keratinocyte differentiation; lipid metabolism; regulation of transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	204219
	545975
	ENSG00000154227
	ENSMUSG00000030510
	Q8IU89
	Q1A3B0
	NM_001290341; NM_001290342; NM_001290343; NM_178842; NM_001378789
	NM_001164201
	NP_001277270; NP_001277271; NP_001277272; NP_849164; NP_001365718
	NP_001157673
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[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 2 3 GRCh38: Ensembl release 89: ENSG00000154227 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030510 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 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.
↑ 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. Bibcode:2005MSRv...24..367H. doi:10.1002/mas.20023. PMID 15389848.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
1 2 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.
↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000154227 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[pmid16753040-5] 1 2 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.

[pmid15389848-6] 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. Bibcode:2005MSRv...24..367H. doi:10.1002/mas.20023. PMID 15389848.

[pmid18541923-7] 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.

[pmid18308723-8] 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.

[RiebelingFuterman2003_Fig5-9] 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.

[pmid17901973-10] 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.

[Mullen_Hannun_2012-11] 1 2 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.

[pmid20222015-12] 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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Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)