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Information on EC 2.3.1.298 - ultra-long-chain ceramide synthase and Organism(s) Mus musculus and UniProt Accession Q1A3B0
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2.3.1.298 ultra-long-chain ceramide synthaseIUBMB Comments
Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 3 (CERS3) is the only enzyme that is active with ultra-long-chain acyl-CoA donors (C28 or longer). It is active in the epidermis, where its products are incorporated into acylceramides. CERS3 also accepts (2R)-2-hydroxy fatty acids and omega-hydroxy fatty acids, and can accept very-long-chain acyl-CoA substrates (see EC 2.3.1.297, very-long-chain ceramide synthase). It can use multiple sphingoid bases including sphinganine, sphingosine, phytosphingosine, and (6R)-6-hydroxysphingosine.
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The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
an ultra-long-chain fatty acyl-CoA
+
=
an ultra-long-chain ceramide
+
Synonyms
(dihydro)ceramide synthase, ceramide synthase, ceramide synthase 3, CerS3, LASS3, LASS3-long, longevity assurance homologue 3, mammalian ceramide synthase 3, phytoceramide synthase, sphingoid base N-ultra-long-chain fatty acyl-coA transferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CerS3
mammalian ceramide synthase 3
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-
-
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sphingoid base N-ultra-long-chain fatty acyl-coA transferase
CerS3
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-
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sphingoid base N-ultra-long-chain fatty acyl-coA transferase
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-
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SYSTEMATIC NAME
IUBMB Comments
ultra-long-chain fatty acyl-coA:sphingoid base N-acyltransferase
Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 3 (CERS3) is the only enzyme that is active with ultra-long-chain acyl-CoA donors (C28 or longer). It is active in the epidermis, where its products are incorporated into acylceramides. CERS3 also accepts (2R)-2-hydroxy fatty acids and omega-hydroxy fatty acids, and can accept very-long-chain acyl-CoA substrates (see EC 2.3.1.297, very-long-chain ceramide synthase). It can use multiple sphingoid bases including sphinganine, sphingosine, phytosphingosine, and (6R)-6-hydroxysphingosine.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
the enzyme exhibits a broad acyl chain preference synthesizing C26-C32 acyl chain ceramides
-
-
?
arachidoyl-CoA + dihydrosphingosine
CoA + N-arachidoyl-dihydrosphingosine
weak activity
-
-
?
behenoyl-CoA + dihydrosphingosine
CoA + N-behenoyldihydrosphingosine
-
-
-
?
cerotoyl-CoA + dihydrosphingosine
CoA + N-cerotoyl-dihydrosphingosine
weak activity
-
-
?
lignoceroyl-CoA + dihydrosphingosine
CoA + N-lignoceroyldihydrosphingosine
-
-
-
?
palmitoyl-CoA + dihydrosphingosine
CoA + N-palmitoyldihydrosphingosine
high activity
-
-
?
stearoyl-CoA + dihydrosphingosine
CoA + N-stearoyldihydrosphingosine
highest activity
-
-
?
an ultra-long-chain fatty acyl-CoA + sphingosine
an ultra-long-chain ceramide + CoA
-
the enzyme uses acyl-CoAs longer than 26 carbon atoms in length
-
-
?
montanoyl-CoA + sphingosine
montanoyl ceramide + CoA
-
bona fide substrate
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
-
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
C26-C34
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
C26-C36
-
-
?
hexacosanoyl-CoA + sphinganine
hexacosanoyl ceramide + CoA
-
main substrate
-
-
?
additional information
?
-
the enzyme exhibits relatively low substrate specificity toward fatty-acyl CoAs
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-
?
additional information
?
-
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the enzyme also accepts long or very long fatty acyl-CoAs as substrate
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-
?
additional information
?
-
-
the enzyme also uses long-chain and very-long-chain fatty acyl-CoAs as substrate
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
the enzyme exhibits a broad acyl chain preference synthesizing C26-C32 acyl chain ceramides
-
-
?
an ultra-long-chain fatty acyl-CoA + sphingosine
an ultra-long-chain ceramide + CoA
-
the enzyme uses acyl-CoAs longer than 26 carbon atoms in length
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
-
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
C26-C34
-
-
?
an ultra-long-chain fatty acyl-CoA + a sphingoid base
an ultra-long-chain ceramide + CoA
-
C26-C36
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acyl-coenzyme A-binding protein
-
increases the activity of the enzyme by 7fold
-
additional information
-
high-speed liver cytosol from wild type mice activates enzyme activity, whereas cytosol from acyl-coenzyme A-binding protein knock-out mice does not
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
aged skin shows decreased levels of stratum corneum ceramides
aged skin shows decreased levels of stratum corneum ceramides. Comparison of activities of epidermal A-SMase, ceramide synthase, and ceramidase in chronologically aged versus young hairless mouse skin. Reduced A-SMase and ceramide synthase activities are found in the epidermis of aged mice, but ceramidase activity is not age-dependent
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the enzyme is expressed in the upper stratum spinosum and stratum granulosumof the skin
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
epidermal ceramides are generated by sphingomyelin hydrolysis or synthesis from sphingosin and fatty acids and are degraded by ceramidase. In aged skin occur decreased levels of stratum corneum ceramides. Epidermal acid sphingomyelinase (A-SMase) generates ceramides with structural function in the stratum corneum lipid bilayers, which provide for the permeability barrier function of the skin. Reduced A-SMase and ceramide synthase activities are found in the epidermis of aged mice, but ceramidase activity is not age-dependent
malfunction
metabolism
-
the enzyme positively regulates very-long chain and ultra-long-chain fatty acid synthesis in keratinocytes. The enzyme regulates activities of ELOVL1 and ELOVL4 in differentiated keratinocytes
malfunction
-
enzyme deficiency in mice results in complete loss of ultra-long-chain acyl moities (C26 or higher), lack of continuous extracellular lipid lamellae and a non-functional cornified lipid envelope. Consequently newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is also prone to Candida albicans infection
malfunction
-
enzyme knockdown causes a reduction in the elongase activities toward ultra-long-chain acyl-CoAs
malfunction
-
enzyme loss leads to tubular atrophy and apoptosis of predominantly primary spermatocytes
malfunction
-
enzyme mutations are associated with skin ichthyosis. Enzyme-deficient mice show death after birth due to transepidermal water loss, hyperkeratosis, deficient cornification, and increased susceptibility to Candida albicans infection
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CERS3_MOUSE
383
5
46081
Swiss-Prot
other Location (Reliability: 5)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme activity is significantly reduced in the testes of acyl-coenzyme A-binding protein-deficient mice
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the enzyme is upregulated first during meiosis and later on in mid-late spermiogenesis, in spermatocytes and in elongated spermatids
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mizutani, Y.; Kihara, A.; Igarashi, Y.
LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity
Biochem. J.
398
531-538
2006
Mus musculus (Q1A3B0)
Park, J.; Park, W.; Futerman, A.
Ceramide synthases as potential targets for therapeutic intervention in human diseases
Biochim. Biophys. Acta
1841
671-681
2014
Mus musculus
Holmes, R.S.; Barron, K.A.; Krupenko, N.I.
Ceramide synthase 6 comparative analysis, phylogeny and evolution
Biomolecules
8
111
2018
Danio rerio (A0A140LFW4), Gallus gallus (F1N8P2), Homo sapiens (Q8IU89), Mus musculus (Q1A3B0)
Jensen, J.M.; Forl, M.; Winoto-Morbach, S.; Seite, S.; Schunck, M.; Proksch, E.; Schutze, S.
Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging
Exp. Dermatol.
14
609-618
2005
Mus musculus (Q1A3B0), Mus musculus SKH-1 (Q1A3B0)
Sandhoff, R.
Very long chain sphingolipids tissue expression, function and synthesis
FEBS Lett.
584
1907-1913
2010
Mus musculus
Jennemann, R.; Rabionet, M.; Gorgas, K.; Epstein, S.; Dalpke, A.; Rothermel, U.; Bayerle, A.; van der Hoeven, F.; Imgrund, S.; Kirsch, J.; Nickel, W.; Willecke, K.; Riezman, H.; Groene, H.J.; Sandhoff, R.
Loss of ceramide synthase 3 causes lethal skin barrier disruption
Hum. Mol. Genet.
21
586-608
2012
Homo sapiens, Mus musculus
Rabionet, M.; Bayerle, A.; Jennemann, R.; Heid, H.; Fuchser, J.; Marsching, C.; Porubsky, S.; Bolenz, C.; Guillou, F.; Groene, H.J.; Gorgas, K.; Sandhoff, R.
Male meiotic cytokinesis requires ceramide synthase 3-dependent sphingolipids with unique membrane anchors
Hum. Mol. Genet.
24
4792-4808
2015
Mus musculus
Ferreira, N.S.; Engelsby, H.; Neess, D.; Kelly, S.L.; Volpert, G.; Merrill, A.H.; Futerman, A.H.; Faergeman, N.J.
Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein
J. Biol. Chem.
292
7588-7597
2017
Mus musculus
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