Mammalian carboxylesterase 3: comparative genomics and proteomics

Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78227, USA.
Genetica (Impact Factor: 1.4). 07/2010; 138(7):695-708. DOI: 10.1007/s10709-010-9438-z
Source: PubMed


At least five families of mammalian carboxylesterases (CES) catalyse the hydrolysis or transesterification of a wide range of drugs and xenobiotics and may also participate in fatty acyl and cholesterol ester metabolism. In this study, in silico methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for CES3 genes and encoded proteins using data from several mammalian genome projects. Mammalian CES3 genes were located within a CES gene cluster with CES2 and CES6 genes, usually containing 13 exons transcribed on the positive DNA strand. Evidence is reported for duplicated CES3 genes for the chimp and mouse genomes. Mammalian CES3 protein subunits shared 58-97% sequence identity and exhibited sequence alignments and identities for key CES amino acid residues as well as extensive conservation of predicted secondary and tertiary structures with those previously reported for human CES1. The human genome project has previously reported CES3 mRNA isoform expression in several tissues, particularly in colon, trachea and in brain. Predicted human CES3 isoproteins were apparently derived from exon shuffling and are likely to be secreted extracellularly or retained within the cytoplasm. Mouse CES3-like transcripts were localized in specific regions of the mouse brain, including the cerebellum, and may play a role in the detoxification of drugs and xenobiotics in neural tissues and other tissues of the body. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the mammalian CES3 family of genes which were related to but distinct from other mammalian CES gene families.

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Available from: Roger Holmes
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    • "Figure 1 summarizes the predicted exonic start sites for cow, opossum, chicken, and zebrafish CEL genes with each having 11 exons, in identical or similar positions to those reported for the human CEL and mouse Cel genes [17, 22, 23]. In contrast, human CES1 [73, 74], CES2, CES3 [75, 76], CES4 [41], and CES5 [77, 78] genes contained 14, 12, 13, 14, and 13 exons, respectively, which are predominantly in distinct positions to those described for vertebrate CEL genes, with the exception of the last exon in each case (Figure  1 of Supplementary Material). Consequently, even though CEL and CES genes and proteins are members of the same serine hydrolase superfamily [10, 40], it is apparent that CEL is not a close relative of the CES gene family, for which at least five genes are clustered on a single chromosomes on human and mouse chromosomes and are more similar in gene structure to each other than they are to the CEL gene (Figure  1 of Supplementary Material; see [41]). "
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    ABSTRACT: Bile-salt activated carboxylic ester lipase (CEL) is a major triglyceride, cholesterol ester and vitamin ester hydrolytic enzyme contained within pancreatic and lactating mammary gland secretions. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures and gene locations for CEL genes, and encoded proteins using data from several vertebrate genome projects. A proline-rich and O-glycosylated 11-amino acid C-terminal repeat sequence (VNTR) previously reported for human and other higher primate CEL proteins was also observed for other eutherian mammalian CEL sequences examined. In contrast, opossum CEL contained a single C-terminal copy of this sequence whereas CEL proteins from platypus, chicken, lizard, frog and several fish species lacked the VNTR sequence. Vertebrate CEL genes contained 11 coding exons. Evidence is presented for tandem duplicated CEL genes for the zebrafish genome. Vertebrate CEL protein subunits shared 53-97% sequence identities; demonstrated sequence alignments and identities for key CEL amino acid residues; and conservation of predicted secondary and tertiary structures with those previously reported for human CEL. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the vertebrate CEL family of genes which were related to a nematode carboxylesterase (CES) gene and five mammalian CES gene families.
    Full-text · Article · Nov 2011 · Cholesterol
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    • "Given the reported role of the N-glycosylated carbohydrate group contributing to CES1 stability and maintaining catalytic efficiency (Kroetz et al. 1993), the Nglycosylation sites predicted for other human CES subunits may perform similar functions or indeed may serve new functions specific to a particular CES family. Predicted secondary structures for human CES2 (Holmes et al. 2009b), CES3 (Holmes et al. 2010), CES4A (Holmes et al. 2009a), and CES5A (Holmes et al. 2008a) sequences were compared with those reported for human CES1, and similar a-helix b-sheet structures were observed for all of the CES subunits examined (Bencharit et al. 2003, 2006) (Fig. 1). This was especially apparent near key residues or functional domains such as the a-helix within the N-terminal signal peptide, the b-sheet and a-helix structures near the active site Ser221 (human CES1) and ''Z-site'' (Glu354/Gly356, respectively), the a-helices bordering the ''side door'' site, and the a-helix containing the ''gate'' residue (Phe550 for human CES1). "
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    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.
    Full-text · Article · Oct 2010 · Mammalian Genome
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