InterPro domain: IPR016439

Yeast ceramide synthase component Lag1 has a paralog, Lac1. This entry includes Lac1, Lag1 and their homologues from plants and animals [ 1 , 2 , 3 ], involved in sphingolipid synthesis.

LAG1 and LAC1 contain multiple membrane-spanning domains and are localised to the endoplasmic reticulum (ER) [ 4 ]. They are essential subunits of the acyl-CoA-dependent ceramide synthase that is involved in synthesis of ceramide from C26(acyl)-coenzyme A and dihydrosphingosine or phytosphingosine [ 5 , 6 , 7 ].

Human Lac1/Lag1 homologue CERS2 (ceramide synthase 2) is a tumour metastasis suppressor that can inhibit breast cancer cell invasion [ 8 ].

Tomato Lac1/Lag1 homologue ASC1 can mediate resistance to sphinganine-analog mycotoxins (SAMs) by restoring the sphingolipid biosynthesis [ 9 ].

Arabidopsis thaliana contains three ceramide synthases with distinct substrate specificities: LOH1 and LOH3 (LONGEVITY ASSURANCE GENE ONE HOMOLOG1 At3g25540 and 3 At1g19260) use very-long-chain fatty acyl-CoA and trihydroxy LCB substrates, and LOH2 (At3g19260) uses palmitoyl-CoA and dihydroxy LCB substrates [ 9 ].

1. The plant disease resistance gene Asc-1 prevents disruption of sphingolipid metabolism during AAL-toxin-induced programmed cell death. Plant J. 32, 561-72
2. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J. Biol. Chem. 277, 35642-9
3. Overexpression of Arabidopsis Ceramide Synthases Differentially Affects Growth, Sphingolipid Metabolism, Programmed Cell Death, and Mycotoxin Resistance. Plant Physiol
4. Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins. Mol. Biol. Cell 10, 1043-59
5. Lip1p: a novel subunit of acyl-CoA ceramide synthase. EMBO J. 24, 730-41
6. Suppressor analysis points to the subtle role of the LAG1 ceramide synthase gene in determining yeast longevity. Exp. Gerontol. 39, 999-1009
7. Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. Mol. Biol. Cell 12, 3417-27
8. CERS2 Suppresses Tumor Cell Invasion and Is Associated with Decreased V-ATPase and MMP-2/MMP-9 activities in Breast Cancer. J. Cell. Biochem. 169, 1108-17