ArticleThe Journal of biological chemistry2012
Acyl chain specificity of ceramide synthases is determined within a region of 150 residues in the Tram-Lag-CLN8 (TLC) domain.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Integrative Multi-omics Analysis for Prioritization of Candidate Genes in Polycystic Ovary Syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- TRAM-LAG1-CLN8 domain-containing protein TMEM56 regulates cell migration by changing intracellular ceramide levels.BMC biology · 2026Article
- [Effect of dephosphorylation of tumor metastasis suppressor geneBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Glia phagocytose neuronal sphingolipids to infiltrate developing synapses.bioRxiv : the preprint server for biology · 2025Article
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Structure and mechanism of a eukaryotic ceramide synthase complex.The EMBO journal · 2023Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Plasma lipidomic profiling reveals metabolic adaptations to pregnancy and signatures of cardiometabolic risk: a preconception and longitudinal cohort study.BMC medicine · 2023Article
- Silencing of ceramide synthase 2 in hepatocytes modulates plasma ceramide biomarkers predictive of cardiovascular death.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Glycosphingolipid metabolism and its role in ageing and Parkinson's disease.Glycoconjugate journal · 2022Review
- 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis.iScience · 2022Article
- Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer.Cancers · 2021Review
- Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype.Cell death & disease · 2021Article
- Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells.Oncoscience · 2021Article
- Whole-Genome and Transposed Duplication Contributes to the Expansion and Diversification ofInternational journal of molecular sciences · 2019Article
- Interrelations of Sphingolipid and Lysophosphatidate Signaling with Immune System in Ovarian Cancer.Computational and structural biotechnology journal · 2019Article
- Ceramide Synthase 6: Comparative Analysis, Phylogeny and Evolution.Biomolecules · 2018Article
- The long and the short of ceramides.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
In mammals, ceramides are synthesized by a family of six ceramide synthases (CerS), transmembrane proteins located in the endoplasmic reticulum, where each use fatty acyl-CoAs of defined chain length for ceramide synthesis. Little is known about the molecular features of the CerS that determine acyl-CoA selectivity. We now explore CerS structure-function relationships by constructing chimeric proteins combining sequences from CerS2, which uses C22-CoA for ceramide synthesis, and CerS5, which uses C16-CoA. CerS2 and -5 are 41% identical and 63% similar. Chimeras containing approximately half of CerS5 (from the N terminus) and half of CerS2 (from the C terminus) were catalytically inactive. However, the first 158 residues of CerS5 could be replaced with the equivalent region of CerS2 without affecting specificity of CerS5 toward C16-CoA; likewise, the putative sixth transmembrane domain (at the C terminus) of CerS5 could be replaced with the corresponding sequence of CerS2 without affecting CerS5 specificity. Remarkably, a chimeric CerS5/2 protein containing the first 158 residues and the last 83 residues of CerS2 displayed specificity toward C16-CoA, and a chimeric CerS2/5 protein containing the first 150 residues and the last 79 residues of CerS5 displayed specificity toward C22-CoA, demonstrating that a minimal region of 150 residues is sufficient for retaining CerS specificity.
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