Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins

Abstract

Mammalian carboxylesterase (CES or Ces) genes encode enzymes that participate in xenobiotic, drug, and lipid metabolism in the body and are members of at least five gene families. Tandem duplications have added more genes for some families, particularly for mouse and rat genomes, which has caused confusion in naming rodent Ces genes. This article describes a new nomenclature system for human, mouse, and rat carboxylesterase genes that identifies homolog gene families and allocates a unique name for each gene. The guidelines of human, mouse, and rat gene nomenclature committees were followed and "CES" (human) and "Ces" (mouse and rat) root symbols were used followed by the family number (e.g., human CES1). Where multiple genes were identified for a family or where a clash occurred with an existing gene name, a letter was added (e.g., human CES4A; mouse and rat Ces1a) that reflected gene relatedness among rodent species (e.g., mouse and rat Ces1a). Pseudogenes were named by adding "P" and a number to the human gene name (e.g., human CES1P1) or by using a new letter followed by ps for mouse and rat Ces pseudogenes (e.g., Ces2d-ps). Gene transcript isoforms were named by adding the GenBank accession ID to the gene symbol (e.g., human CES1_AB119995 or mouse Ces1e_BC019208). This nomenclature improves our understanding of human, mouse, and rat CES/Ces gene families and facilitates research into the structure, function, and evolution of these gene families. It also serves as a model for naming CES genes from other mammalian species.

Fig. 1

Amino acid sequence alignments for human CES1, CES2, CES3, CES4A, and CES5A subunits. See Table 1 for CES isoform sequences aligned. Asterisk identical residues for CES subunits; colon similar alternate residues; dot dissimilar alternate residues. Signal peptide sequences for CES1 (1–17), CES2 (1–25), CES3 (1–27), CES4A (1–19), and CES5A (1–24) and C- termini (MTS) microsomal targeting sequences for CES1 (564–567), CES2 (556–569), and CES3 (568–571) are shown in red. Active site (AS) triad residues (human CES1) Ser221, Glu354, and His468 are highlighted in green. “Side door” (Val424-Met425-Phe426), “Gate” (Phe550), and cholesterol binding residue (“Z site”) (Gly356) for human CES1 (Fleming et al. 2005) are highlighted in khaki. Disulfide bond Cys residues for human CES1 (filled circle) are shown in blue. Charge clamp residues identified for human CES1 (Glu72…Arg186; Lys78…Glu183) (Fleming et al. 2005) are highlighted in purple. Confirmed (CES1) (Asn79-Ala80-Thr81) [site 1] or predicted N-glycosylation sites for human CES2 (Asn111-Met112-Thr113) [site 3]; CES3 (Asn105-Ser106-Ser107) [site 2]; CES4A (Asn213-Val214-Thr215) [site 4], Asn276-Ser-277-Thr278) [site 5], and Asn388-Ile389-Thr390) [site 7]; and CES5A (Asn363-Lys364-Ser365) [site 6], (Asn513-Leu514-Thr515) [site 8], and (Asn524-Met525-Ser526 [site 9] are highlighted in blue. α-Helix (human CES1 or predicted) and β-sheet (human CES1 or predicted) regions are highlighted in yellow and gray, respectively. α-Helices and β-sheets are numbered according to the reported human CES1 3D structure (Fleming et al. 2005). Bold underlined font shows known or predicted exon start sites; exon numbers refer to the human CES1 gene (see Langmann et al. 1997). (Color figure online)

Fig. 2

Gene structures and major isoforms for human CES1, CES2, CES3, CES4A, and CES5A genes. Derived from AceView website http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/ (Thierry-Mieg and Thierry-Mieg 2006). Mature isoform variants (a) are shown with capped 5′ and 3′ ends for the predicted mRNA sequences. Exons are in solid color. 5′ and 3′ untranslated regions of the genes are shown as open boxes. Introns are shown as a line. The 5′ → 3′ transcription directions are shown. a refers to the major transcript isoform for each human CES gene. Note that each CES gene structure is drawn to a different scale and that the respective gene sizes are shown: CES1, 34.8 kb; CES2, 10.9 kb; CES3, 13.9 kb; CES4A, 22.3 kb; and CES5A, 79.3 kb. (Color figure online)