Recombinant Human Ceramide synthase 6 (CERS6)
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Description
Functional Roles in Sphingolipid Metabolism
CERS6 regulates the balance of ceramide species, impacting membrane integrity and signaling:
Table 2: Ceramide Species Generated by CERS6
Overexpression of CERS6 shifts ceramide pools toward C16:0 at the expense of very long-chain (C22–C26) ceramides, altering sphingomyelin composition and downstream signaling .
Disease Associations and Mechanisms
Recombinant CERS6 studies have elucidated its role in multiple pathologies:
Table 3: CERS6 in Disease Pathogenesis
Therapeutic Targeting and Research Applications
Recombinant CERS6 is pivotal in drug discovery and mechanistic studies:
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Structural Insights: Cryo-EM structures (PDB: 8QZ6) guide inhibitor design targeting the His211 active site .
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Biomarker Potential: Elevated CERS6 mRNA/protein levels correlate with poor chemotherapy response in T-ALL .
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Gene Silencing: shRNA-mediated knockdown in diabetic models reduces renal fibrosis and ceramide accumulation .
Key Research Findings
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Catalytic Mechanism: CERS6 transfers acyl chains via a covalent histidine intermediate, a target for small-molecule inhibitors .
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Apoptosis Regulation: Modulates extrinsic apoptosis by binding CD95/Fas and disrupting DISC assembly in T-ALL .
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Metabolic Reprogramming: In melanoma, CERS6 silencing upregulates HK, M2-PK, and LDHA activity, enhancing glycolysis .
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Mitophagy Link: C16:0 ceramide accumulation in diabetic kidneys suppresses PINK1-dependent mitophagy, driving fibrosis .
Product Specs
Form
Lyophilized powder
Note: While we prioritize shipping the format currently in stock, please specify any format requirements in your order notes for customized preparation.
Note: While we prioritize shipping the format currently in stock, please specify any format requirements in your order notes for customized preparation.
Lead Time
Delivery times vary depending on the purchase method and location. Please consult your local distributor for precise delivery timelines.
Note: All proteins are shipped with standard blue ice packs unless dry ice shipping is specifically requested and agreed upon in advance. Additional fees apply for dry ice shipping.
Note: All proteins are shipped with standard blue ice packs unless dry ice shipping is specifically requested and agreed upon in advance. Additional fees apply for dry ice shipping.
Notes
Avoid repeated freeze-thaw cycles. Store working aliquots at 4°C for up to one week.
Reconstitution
Centrifuge the vial briefly before opening to collect the contents. Reconstitute the protein in sterile, deionized water to a concentration of 0.1-1.0 mg/mL. For long-term storage, we recommend adding 5-50% glycerol (final concentration) and aliquoting at -20°C/-80°C. Our standard glycerol concentration is 50%, which can serve as a reference.
Shelf Life
Shelf life depends on storage conditions, buffer composition, temperature, and protein stability. Generally, liquid formulations have a 6-month shelf life at -20°C/-80°C, while lyophilized formulations have a 12-month shelf life at -20°C/-80°C.
Storage Condition
Upon receipt, store at -20°C/-80°C. Aliquoting is essential for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag type is determined during manufacturing.
The tag type is determined during the production process. If a specific tag type is required, please inform us, and we will prioritize its development.
The tag type is determined during the production process. If a specific tag type is required, please inform us, and we will prioritize its development.
Synonyms
CERS6; LASS6; Ceramide synthase 6; CerS6; LAG1 longevity assurance homolog 6; Sphingoid base N-palmitoyltransferase CERS6
Buffer Before Lyophilization
Tris/PBS-based buffer, 6%
Trehalose.
Datasheet
Please contact us to get it.
Expression Region
1-384
Protein Length
full length protein
Species
Homo sapiens (Human)
Target Names
CERS6
Target Protein Sequence
MAGILAWFWNERFWLPHNVTWADLKNTEEATFPQAEDLYLAFPLAFCIFMVRLIFERFVA
KPCAIALNIQANGPQIAPPNAILEKVFTAITKHPDEKRLEGLSKQLDWDVRSIQRWFRQR
RNQEKPSTLTRFCESMWRFSFYLYVFTYGVRFLKKTPWLWNTRHCWYNYPYQPLTTDLHY
YYILELSFYWSLMFSQFTDIKRKDFGIMFLHHLVSIFLITFSYVNNMARVGTLVLCLHDS
ADALLEAAKMANYAKFQKMCDLLFVMFAVVFITTRLGIFPLWVLNTTLFESWEIVGPYPS
WWVFNLLLLLVQGLNCFWSYLIVKIACKAVSRGKVSKDDRSDIESSSDEEDSEPPGKNPH
TATTTNGTSGTNGYLLTGSCSMDD
Uniprot No.
Target Background
Function
Ceramide synthase 6 (CERS6) catalyzes the transfer of an acyl chain from acyl-CoA to a sphingoid base, exhibiting high selectivity for palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA). While it can utilize other acyl donors, efficiency is reduced. CERS6 N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides, respectively, participating in both de novo synthesis and salvage pathways. The ceramides produced by CERS6 play a crucial role in inflammatory responses, and regulate metabolism and hepatic lipid accumulation. Under high-fat diets, CERS6-generated palmitoyl- (C16:0-) ceramides specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to obesity development.
Gene References Into Functions
- Studies demonstrate that SphK1 overexpression and S1P addition increase mTOR phosphorylation (ELISA), while S1PR2 inhibition has the opposite effect. This suggests that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. mTOR activity is influenced by the balance between S1P and C16-ceramide, which is generated by CerS6. PMID: 30226616
- Ceramide synthase (CerS) 6 was specifically upregulated in zone 3 hepatocytes in alcoholic steatosis. PMID: 28864659
- p53 upregulates CerS6 through direct transcriptional activation, thereby regulating specific ceramide biosynthesis and contributing to the pro-apoptotic cellular response. PMID: 27302066
- CerS6 silencing increased GLUT1 expression, downregulated WNT5A, and enhanced melanoma cell invasion and proliferation. PMID: 26934938
- CerS6 and ceramide pathways have been identified as a novel Methotrexate target. PMID: 26783755
- Ceramide synthase phosphorylation may be a key regulatory mechanism controlling the distribution and levels of sphingolipids with varying acyl-chain lengths. PMID: 26887952
- Stichoposide D inhibits experimental leukemia growth by activating Fas/ceramide synthase 6/p38 kinase in lipid rafts. PMID: 26318294
- CERS6-dependent ceramide synthesis and membrane ceramide maintenance are essential for lamellipodia formation and metastasis. PMID: 26650179
- Ceramide synthase 6 (CerS6) expression is upregulated in leukocytes from multiple sclerosis (MS) patients. PMID: 25833068
- CERS6's pivotal role in regulating cell death in COX dysfunction suggests its potential as a therapeutic target for mitochondrial diseases resulting from COX dysfunction. PMID: 25766330
- Increased CerS6 expression mediates transcriptional activation of acid ceramidase in a JNK-dependent manner, independent of CerS6 activity. PMID: 25839235
- CerS6 is an epithelial-mesenchymal transition-regulated gene that plays a crucial role in cell migration regulation. PMID: 24632610
- CERS6 upregulation in an experimental autoimmune encephalomyelitis model is sex-dependent. PMID: 25173988
- Co-expression of CerS2 with CerS4/CerS6 reversed the inhibitory effect of long-chain ceramides on cell proliferation and apoptosis induction. PMID: 23538298
- Folate withdrawal induced CerS6/C16-ceramide elevation and p53 accumulation, linking folate and de novo ceramide pathways in cellular stress response. PMID: 23519469
- Transient CerS6 upregulation correlates with increased C(16:0)-Cer levels in the cerebrospinal fluid of multiple sclerosis patients. PMID: 22544924
- CerS6/C16-ceramide alteration induces ATF6-mediated endoplasmic reticulum (ER) stress and apoptosis via changes in cellular Ca2+ and the ER/Golgi membrane network. PMID: 22013072
- Ionizing radiation induces de novo ceramide synthesis, activating CerS isoforms 2, 5, and 6, which produce opposing anti- and pro-apoptotic ceramides in mitochondrial membranes. PMID: 20406683
- Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) PMID: 20379614
- CerS2 and CerS6 mRNA were significantly elevated in breast cancer tissue compared to normal tissue, with approximately half of the individuals showing elevated CerS2 and CerS6 mRNA. PMID: 19912991
- mda-7/IL-24 induces PERK activation, triggering ceramide, ceramide synthase 6, and thioredoxin production, which promote glioma cell autophagy and cell death. PMID: 20103619
- CerS6/C(16)-ceramide regulates ER-stress-induced apoptosis via the ATF6/CHOP arm of the unfolded protein response pathway. PMID: 19723703
Database Links
Subcellular Location
Endoplasmic reticulum membrane; Multi-pass membrane protein.
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