Ceramide Synthase 6: Comparative Analysis, Phylogeny and Evolution.

Ceramide synthase 6 (, also known as ) is one of the six members of ceramide synthase gene family in humans. Comparisons of CerS6 amino acid sequences and structures as well as of gene structures/locations were conducted using data from several vertebrate genome projects. A specific role for the gene and protein has been identified as the endoplasmic reticulum C- and C-ceramide synthase. Mammalian CerS6 proteins share 90⁻100% similarity among different species, but are only 22⁻63% similar to other CerS family members, suggesting that is a distinct gene family. Sequence alignments, predicted transmembrane, lumenal and cytoplasmic segments and N-glycosylation sites were also investigated, resulting in identification of the key conserved residues, including the active site as well as C-terminus acidic and serine residues. Mammalian genes contain ten exons, are primarily located on the positive strands and transcribed as two major isoforms. The human gene promoter harbors a large CpG island (94 CpGs) and multiple transcription factor binding sites (TFBS), which support precise transcriptional regulation and signaling functions. Additional regulation is conferred by 15 microRNA (miRNA) target sites identified in the 3'-UTR region. Phylogenetic analysis of the vertebrate gene families relationships supports a major role for the CerS6 enzyme that is strongly conserved throughout vertebrate evolution.