Protein: Ceramide synthase 1 (CerS1) (LAG1 longevity assurance homolog 1) (Longevity assurance gene 1 protein homolog 1) (Protein UOG-1) (Sphingoid base N-stearoyltransferase CERS1) (EC 2.3.1.299) (P27544)
Organism: Homo sapiens (Human)
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). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively. 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.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:24782409}; Multi-pass membrane protein {ECO:0000255}.
Sequence: MAAAGPAAGPTGPEPMPSYAQLVQRGWGSALAAARGCTDCGWGLARRGLAEHAHLAPPELLLLALGALGWTALRSAATARLFRPLAKRCCLQPRDAAKMPESAWKFLFYLGSWSYSAYLLFGTDYPFFHDPPSVFYDWTPGMAVPRDIAAAYLLQGSFYGHSIYATLYMDTWRKDSVVMLLHHVVTLILIVSSYAFRYHNVGILVLFLHDISDVQLEFTKLNIYFKSRGGSYHRLHALAADLGCLSFGFSWFWFRLYWFPLKVLYATSHCSLRTVPDIPFYFFFNALLLLLTLMNLYWFLYIVAFAAKVLTGQVHELKDLREYDTAEAQSLKPSKAEKPLRNGLVKDKRF
InterPro domains: - IPR006634: TRAM/LAG1/CLN8 homology domain (domain) [97-311]
- IPR016439: Sphingosine N-acyltransferase Lag1/Lac1-like (family) [46-330]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0005515 (protein binding), GO:0016746 (acyltransferase activity), GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl groups), GO:0016410 (N-acyltransferase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0006629 (lipid metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0043603 (amide metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:0006643 (membrane lipid metabolic process), GO:0006672 (ceramide metabolic process), GO:0043604 (amide biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0046467 (membrane lipid biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0006665 (sphingolipid metabolic process), GO:0046513 (ceramide biosynthetic process), GO:0030148 (sphingolipid biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031984 (organelle subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0031090 (organelle membrane), GO:0005783 (endoplasmic reticulum), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0098827 (endoplasmic reticulum subcompartment), GO:0043231 (intracellular membrane-bounded organelle), GO:0005789 (endoplasmic reticulum membrane)