Genomic organization, sequence analysis, and chromosomal localization of the human car☐yl ester lipase (CEL) gene and a CEL-like (CELL) gene

University of Gothenburg, Goeteborg, Västra Götaland, Sweden
Genomics (Impact Factor: 2.28). 08/1992; 13(3):630-40. DOI: 10.1016/0888-7543(92)90134-E
Source: PubMed

ABSTRACT The gene encoding human carboxyl ester lipase (CEL), including 1628 bp of the 5'-flanking region, has been isolated and characterized from two overlapping lambda phage clones. The gene spans 9832 bp and contains 11 exons interrupted by 10 introns. The exons range in size from 88 to 204 bp, except for the last exon, which is 841 bp. A major and a minor transcription initiation site were determined 13 and 7 bp, respectively, upstream of the initiator methionine. The nucleotide sequence is identical with that of the previously reported cDNA, except for the third nucleotide in the 5'-untranslated sequence, a C, which in the cDNA is a T. A TAAATA sequence is present 26 nt upstream from the major CAP site, and within the 5'-flanking region there are several putative transcription factor binding sites. Seven Alu repetitive sequence elements are present in the region analyzed. The organization of the human CEL gene is similar to that of the recently reported rat pancreatic cholesterol esterase gene. The CEL gene was assigned to chromosome 9q34-qter, which confirms the recently reported results of Tayler et al. (1991, Genomics 10: 425-431). A previously unknown gene with a striking homology to the human CEL gene, here called the CEL-like gene (CELL), has also been isolated and characterized, including 1724 bp of the 5'-flanking region. The CELL gene, which most likely is a psuedogene, spans 4846 bp, and due to the absence of a 4.8-kb segment, the CEL gene exons 2-7 are not present in the CELL gene. Despite these differences, the CELL gene is transcribed. We have also assigned the CELL gene to a separate locus at chromosome 9q34-qter.

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    • "Moreover, reverse cholesterol transport is elevated in carboxyl ester lipase-knockout mice which supports a significant role for this enzyme in the biliary disposal of cholesterol from the body [14]. A CEL-like gene (designated as CELL) has also been identified on human and gorilla chromosome 9, about 10 kilobases downstream of CEL, which is transcribed in many tissues of the body but lacks exons 2–7 and is unlikely to be translated into protein [17] [20] [35]. The CELL pseudogene gene duplication apparently occurred prior to the separation of Hominidae (man, chimpanzee, gorilla, and orangutan) from Old World monkeys (macaque) with CELL being restricted to genomes of man and the great apes [20]. "
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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.
    Cholesterol 11/2011; 2011:781643. DOI:10.1155/2011/781643
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    • "Lidberg and colleagues previously identified the carboxyl ester lipase-like gene (CELL, genbank accession number M94580) with high homology to the BSSL gene [36]. CELL contains a VNTR domain resembling the exon 11 VNTR domain of BSSL although Lidberg and colleagues reported the CELL VNTR to contain 7 repeats less than BSSL. "
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    ABSTRACT: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms. ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions. DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein. The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding.
    PLoS ONE 02/2011; 6(2):e17316. DOI:10.1371/journal.pone.0017316 · 3.23 Impact Factor
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    • "Therefore, investigation into the association between polymorphisms in genes that regulate intestinal triglyceride and cholesterol digestion and plasma lipoprotein outcomes in response to soluble fi ber consumption may be prudent. Indeed, pancreatic triglyceride lipase and carboxyl ester lipase, two enzymes involved in intestinal triglyceride and cholesterol digestion, have been shown to be highly polymorphic and may therefore explain some of the variability associated with dietary fiber consumption (Lidberge et al 1992; Cao and Hegele 2003). "
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    ABSTRACT: The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in 'high-dimensional' biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of 'omic' technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based "cocktails" that target specific metabolic pathways to gain maximal cholesterol reductions.
    Vascular Health and Risk Management 02/2008; 4(5):1023-33.
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