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Enzyme Nomenclature
Information on EC 2.3.1.291 - sphingoid base N-palmitoyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9HA82
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2.3.1.291 sphingoid base N-palmitoyltransferaseIUBMB Comments
Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 5 (CERS5) is specific for palmitoyl-CoA as the acyl donor. It can use multiple sphingoid bases including sphinganine, sphingosine, and phytosphingosine.
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CerS5
LASS5
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mammalian ceramide synthase 5
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CerS5
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
palmitoyl-CoA:sphingoid base N-palmitoyltransferase
Mammals have six ceramide synthases that exhibit relatively strict specificity regarding the chain-length of their acyl-CoA substrates. Ceramide synthase 5 (CERS5) is specific for palmitoyl-CoA as the acyl donor. It can use multiple sphingoid bases including sphinganine, sphingosine, and phytosphingosine.
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
additional information
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expression of CERS5 increases the level of C16:0-ceramide and decreases levels of C18:0-ceramide, C22:0-ceramide, and C24-ceramides
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
an age-dependent decline of both isoforms CerS1 and CerS5 mRNA expression is observed in skeletal muscle biopsies
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
CerS5 activity is inhibited in a dominant-negative fashion by co-expression with catalytically inactive CerS5, and isoform CerS2 activity is enhanced by co-expression with a catalytically active form of CerS5 or CerS6. In a constitutive heterodimer comprising CerS5 and CerS2, the activity of CerS2 depends on the catalytic activity of CerS5. CerS dimers are formed upon rapid stimulation of ceramide synthesis by curcumin
physiological function
ionizing radiation induces de novo synthesis of ceramide to influence HeLa cell apoptosis by specifically activating CerS isoforms 2, 5, and 6 that generate opposing anti- and pro-apoptotic ceramides in mitochondrial membranes. Isoforms CerS5 and CerS6 each confer about 50% of the C16:0 CerS baseline synthetic activity, both are required for ionizing radiation-induced activity. Isoforms CerS2, 5, and 6 might exist as heterocomplexes in HeLa cells
physiological function
Lass5 interacts with succinate dehydrogenase subunit B. The C-terminal fragment of succinate dehydrogenase subunit B is required for the interaction. Lass5 and succinate dehydrogenase subunit B co-localize in COS-7 cells. Lass5 and succinate dehydrogenase subunit B expressions are up-regulated in neuroglioma tissue, and Lass5 or succinate dehydrogenase subunit B expression represses p53 or p21 reporter activity, respectively
physiological function
overexpression of isoform Cers5 leads to accumulation of C16:0 ceramides. Presence of insulin has no effect on sphingomyelins, while palmitate treatment causes a significant decrease in several species, including the predominant C16:0 species. CerS5 knockdown reduces glycogen synthesis in the absence or presence of palmitate. Isoform CerS1 overexpression results in minor upregulation of endogenous CerS5
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). POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
phosphorylation modestly increases the catalytic activities of Cers5
phosphoprotein
isoform Cers5 is phosphorylated at the cytoplasmic C-terminal region. Treatment with lambda protein phosphatase reduces the activity by 27%
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
a mutant based on the backbone of CerS5 (which generates C16-ceramide), containing an 11-residue sequence of a loop located between the last two putative transmembrane domainsfrom CerS2 (which generates C22-C24-ceramides), is altered such that it generates C22-C24 and other ceramides. The mutant generates C22:0-ceramide and C16:0-ceramide to a similar extent but also generates C18:0-, C20:0-, and C24:1-ceramides
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
ionizing radiation induces de novo synthesis of ceramide by specifically activating CerS isoforms 2, 5, and 6
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
medicine
both isoforms CerS4 and CerS5 are up-regulated in endometrial and colon cancer cells. Apoptosis induction by anastrozole or 5-FU results in down-regulation of CerS4 and CerS5 in endometrial and colon cancer cells
medicine
in human breast cancer tissue, a significant increase in CerS4 and CerS6 mRNA is observed in estrogen receptor positive cancer tissue. The activities of CerS4 and CerS5 promoter constructs increase after estradiol treatment in MCF-7 cells. Estradiol and GPER1 mediate their effects on CerS4 and Cers5 promoter by activating AP-1, most likely through dimerization of c-Jun and c-Fos
medicine
both isoforms CerS4 and CerS5 are up-regulated in endometrial and colon cancer cells. Apoptosis induction by anastrozole or 5-FU results in down-regulation of CerS4 and CerS5 in endometrial and colon cancer cells
medicine
CerS1 and CerS5 mRNA expression is reduced in muscle biopsies from patients in advanced stage of chronic heart failure suffering from muscle wasting and frailty
medicine
in human breast cancer tissue, a significant increase in CerS4 and CerS6 mRNA isobserved in estrogen receptor positive cancer tissue. The activities of CerS4 and CerS5 promoter constructs increase after estradiol treatment in MCF-7 cells. Estradiol and GPER1 mediate their effects on CerS4 and Cers5 promoter by activating AP-1, most likely through dimerization of c-Jun and c-Fos
medicine
in human wild-type p53 HCT-116 colon cancer cells, treatment with oxaliplatin or 5-fluorouracil leads to a strong increase in ceramide synthase CerS5 expression and C16:0-ceramide levels, which is not seen in HCT-116 cells lacking p53 expression. The increase in CerS5 expression occurs by stabilizing CerS5 mRNA at the 3'-UTR
medicine
long-chain ceramides are upregulated whereas very long-chain ceramides are downregulated in cell lines, mouse animal model, and patients with cystic fibrosis, compared with their controls. Treatment with fenretinide decreases the levels of long-chain ceramides and increases the levels of very long-chain ceramides
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Tosetti, B.; Brodesser, S.; Brunn, A.; Deckert, M.; Blueher, M.; Doehner, W.; Anker, S.D.; Wenzel, D.; Fleischmann, B.; Pongratz, C.; Peters, F.; Utermoehlen, O.; Kroenke, M.
A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle
Aging Cell
19
e13049
2019
Homo sapiens (Q8N5B7), Mus musculus (Q9D6K9)
Wegner, M.S.; Wanger, R.A.; Oertel, S.; Brachtendorf, S.; Hartmann, D.; Schiffmann, S.; Marschalek, R.; Schreiber, Y.; Ferreiros, N.; Geisslinger, G.; Groesch, S.
Ceramide synthases CerS4 and CerS5 are upregulated by 17beta-estradiol and GPER1 via AP-1 in human breast cancer cells
Biochem. Pharmacol.
92
577-589
2014
Homo sapiens (Q8N5B7), Homo sapiens (Q9HA82)
Brachtendorf, S.; Wanger, R.A.; Birod, K.; Thomas, D.; Trautmann, S.; Wegner, M.S.; Fuhrmann, D.C.; Bruene, B.; Geisslinger, G.; Groesch, S.
Chemosensitivity of human colon cancer cells is influenced by a p53-dependent enhancement of ceramide synthase 5 and induction of autophagy
Biochim. Biophys. Acta
1863
1214-1227
2018
Homo sapiens (Q8N5B7)
Mesicek, J.; Lee, H.; Feldman, T.; Jiang, X.; Skobeleva, A.; Berdyshev, E.V.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R.
Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells
Cell. Signal.
22
1300-1307
2010
Homo sapiens (Q8N5B7)
Jiang, Z.; Li, F.; Wan, Y.; Han, Z.; Yuan, W.; Cao, L.; Deng, Y.; Peng, X.; Chen, F.; Fan, X.; Liu, X.; Dai, G.; Wang, Y.; Zeng, Q.; Shi, Y.; Zhou, Z.; Chen, Y.; Xu, W.; Luo, S.; Chen, S.; Ye, X.; Mo, X.; Wu, X.; Li, Y.
LASS5 interacts with SDHB and synergistically represses p53 and p21 activity
Curr. Mol. Med.
16
582-590
2016
Homo sapiens (Q8N5B7)
Frangioudakis, G.; Diakanastasis, B.; Liao, B.Q.; Saville, J.T.; Hoffman, N.J.; Mitchell, T.W.; Schmitz-Peiffer, C.
Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to those caused by palmitate treatment
Diabetologia
56
2697-701
2013
Homo sapiens (Q8N5B7)
Mojakgomo, R.; Mbita, Z.; Dlamini, Z.
Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and colon cancers
Exp. Mol. Pathol.
98
585-592
2015
Homo sapiens (Q8N5B7), Homo sapiens (Q9HA82)
Laviad, E.L.; Kelly, S.; Merrill, A.H.; Futerman, A.H.
Modulation of ceramide synthase activity via dimerization
J. Biol. Chem.
287
21025-21033
2012
Homo sapiens (Q8N5B7)
Sassa, T.; Hirayama, T.; Kihara, A.
Enzyme activities of the ceramide synthases CERS2-6 are regulated by phosphorylation in the C-terminal region
J. Biol. Chem.
291
7477-7487
2016
Homo sapiens (Q8N5B7), Mus musculus (Q9D6K9)
Garic, D.; De Sanctis, J.B.; Wojewodka, G.; Houle, D.; Cupri, S.; Abu-Arish, A.; Hanrahan, J.W.; Hajduch, M.; Matouk, E.; Radzioch, D.
Fenretinide differentially modulates the levels of long- and very long-chain ceramides by downregulating Cers5 enzyme evidence from bench to bedside
J. Mol. Med.
95
1053-1064
2017
Homo sapiens (Q8N5B7), Mus musculus (Q9D6K9)
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