CERS1
Function
Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:17977534, PubMed:23530041, PubMed:24782409, PubMed:26887952, PubMed:31916624). Plays a predominant role in skeletal muscle in regulating C18 ceramide and dihydroceramide levels with an impact on whole-body glucose metabolism and insulin sensitivity. Protects from diet-induced obesity by suppressing the uptake of glucose in multiple organs in a FGF21-dependent way (By similarity). Generates C18 ceramides in the brain, playing a critical role in cerebellar development and Purkinje cell function (By similarity). In response to cellular stress mediates mitophagy, a known defense mechanism against cell transformation and aging. Upon mitochondria fission, generates C18 ceramides that anchor lipidated MAP1LC3B/LC3B-II autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria (PubMed:22922758).
Involvement in disease
Epilepsy, progressive myoclonic 8
EPM8
A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. EPM8 is an autosomal recessive form characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Lipid metabolism; sphingolipid metabolism.
Post-translational modifications
Acetylated. Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
Alternative names
LAG1, LASS1, UOG1, CERS1, Ceramide synthase 1, CerS1, LAG1 longevity assurance homolog 1, Longevity assurance gene 1 protein homolog 1, Protein UOG-1, Sphingoid base N-stearoyltransferase CERS1