Author Report for: Cox LANo contact information in database for Cox LA
Holmes RS, Vandeberg JL, Cox LA Ref: Genetica, 139:291, 2011 : PubMed ESTHER: Holmes_2011_Genetica_139_291 PubMedSearch: Holmes 2011 Genetica 139 291 PubMedID: 21267636 Abstract Endothelial lipase (gene: LIPG; enzyme: EL) is one of three members of the triglyceride lipase family that contributes to lipoprotein degradation within the circulation system and plays a major role in HDL metabolism in the body. In this study, in silico methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for LIPG genes and encoded proteins using data from several vertebrate genome projects. LIPG is located on human chromosome 18 and is distinct from other human 'neutral lipase' genes, hepatic lipase (gene: LIPC; enzyme: HL) and lipoprotein lipase (gene: LPL; enzyme: LPL) examined. Vertebrate LIPG genes usually contained 10 coding exons located on the positive strand for most primates, as well as for horse, bovine, opossum, platypus and frog genomes. The rat LIPG gene however contained only 9 coding exons apparently due to the presence of a 'stop' codon' within exon 9. Vertebrate EL protein subunits shared 58-97% sequence identity as compared with 38-45% sequence identities with human HL and LPL. Four previously reported human EL N-glycosylation sites were predominantly conserved among the 10 potential N-glycosylation sites observed for the vertebrate EL sequences examined. Sequence alignments and identities for key EL amino acid residues were observed as well as conservation of predicted secondary and tertiary structures with those previously reported for horse pancreatic lipase (PL) (Bourne et al. 1994). Several potential sites for regulating LIPG gene expression were observed including CpG islands near the LIPG gene promoter and a predicted microRNA binding site near the 3'-untranslated region. Promoter regions containing functional polymorphisms that regulate HDL cholesterol in baboons were conserved among primates but not retained between primates and rodents. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate LIPG gene subfamily with other neutral triglyceride lipase gene families, LIPC and LPL. It is apparent that the triglyceride lipase ancestral gene for the vertebrate LIPG gene predated the appearance of fish during vertebrate evolution >500 million years ago. Title: Comparative Structures and Evolution of Vertebrate Carboxyl Ester Lipase (CEL) Genes and Proteins with a Major Role in Reverse Cholesterol Transport Holmes RS, Cox LA Ref: Cholesterol, 2011:781643, 2011 : PubMed ESTHER: Holmes_2011_Cholesterol_2011_781643 PubMedSearch: Holmes 2011 Cholesterol 2011 781643 PubMedID: 22162806 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. Title: Comparative studies of vertebrate lipoprotein lipase: a key enzyme of very low density lipoprotein metabolism Holmes RS, Vandeberg JL, Cox LA Ref: Comparative Biochemistry & Physiology Part D Genomics Proteomics, 6:224, 2011 : PubMed ESTHER: Holmes_2011_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_6_224 PubMedSearch: Holmes 2011 Comp.Biochem.Physiol.Part.D.Genomics.Proteomics 6 224 PubMedID: 21561822 Abstract Lipoprotein lipase (LIPL or LPL; E.C.3.1.1.34) serves a dual function as a triglyceride lipase of circulating chylomicrons and very-low-density lipoproteins (VLDL) and facilitates receptor-mediated lipoprotein uptake into heart, muscle and adipose tissue. Comparative LPL amino acid sequences and protein structures and LPL gene locations were examined using data from several vertebrate genome projects. Mammalian LPL genes usually contained 9 coding exons on the positive strand. Vertebrate LPL sequences shared 58-99% identity as compared with 33-49% sequence identities with other vascular triglyceride lipases, hepatic lipase (HL) and endothelial lipase (EL). Two human LPL N-glycosylation sites were conserved among seven predicted sites for the vertebrate LPL sequences examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied. A CpG island was identified within the 5'-untranslated region of the human LPL gene which may contribute to the higher than average (x4.5 times) level of expression reported. Phylogenetic analyses examined the relationships and potential evolutionary origins of vertebrate lipase genes, LPL, LIPG (encoding EL) and LIPC (encoding HL) which suggested that these have been derived from gene duplication events of an ancestral neutral lipase gene, prior to the appearance of fish during vertebrate evolution. Comparative divergence rates for these vertebrate sequences indicated that LPL is evolving more slowly (2-3 times) than for LIPC and LIPG genes and proteins. Title: Vertebrate hepatic lipase genes and proteins: a review supported by bioinformatic studies Holmes RS, Vandeberg JL, Cox LA Ref: Open Access Bioinformatics, 2011:85, 2011 : PubMed ESTHER: Holmes_2011_Open.Access.Bioinformatics_2011_85 PubMedSearch: Holmes 2011 Open.Access.Bioinformatics 2011 85 PubMedID: 22408368 Abstract Hepatic lipase (gene: LIPC; enzyme: HL; E.C.3.1.1.3) is one of three members of the triglyceride lipase family that contributes to vascular lipoprotein degradation and serves a dual role in triglyceride hydrolysis and in facilitating receptor-mediated lipoprotein uptake into the liver. Amino acid sequences, protein structures, and gene locations for vertebrate LIPC (or Lipc for mouse and rat) genes and proteins were sourced from previous reports and vertebrate genome databases. Lipc was distinct from other neutral lipase genes (Lipg encoding endothelial lipase and Lpl encoding lipoprotein lipase [LPL]) and was located on mouse chromosome 9 with nine coding exons on the negative strand. Exon 9 of human LIPC and mouse and rat Lipc genes contained "stop codons" in different positions, causing changes in C-termini length. Vertebrate HL protein subunits shared 58%-97% sequence identities, including active, signal peptide, disulfide bond, and N-glycosylation sites, as well as proprotein convertase ("hinge") and heparin binding regions. Predicted secondary and tertiary structures revealed similarities with the three-dimensional structure reported for horse and human pancreatic lipases. Potential sites for regulating LIPC gene expression included CpG islands near the 5''-untranslated regions of the mouse and rat LIPC genes. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate LIPC gene family with other neutral triglyceride lipase gene families (LIPG and LPL). We conclude that the triglyceride lipase ancestral gene for vertebrate neutral lipase genes (LIPC, LIPG, and LPL) predated the appearance of fish during vertebrate evolution. Title: Comparative studies of mammalian acid lipases: Evidence for a new gene family in mouse and rat (Lipo) Holmes RS, Cox LA, Vandeberg JL Ref: Comparative Biochemistry & Physiology Part D Genomics Proteomics, 5:217, 2010 : PubMed ESTHER: Holmes_2010_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_5_217 PubMedSearch: Holmes 2010 Comp.Biochem.Physiol.Part.D.Genomics.Proteomics 5 217 PubMedID: 20598663 Gene_locus related to this paper: human-LIPF, human-LIPJ, human-LIPK, human-LIPM, human-LIPN, mouse-LIPK Abstract At least six families of mammalian acid lipases (E.C. 3.1.1.-) catalyse the hydrolysis of triglycerides in the body, designated as LIPA (lysosomal), LIPF (gastric), LIPJ (testis) and LIPK, LIPM and LIPN (epidermal), which belong to the AB hydrolase superfamily. In this study, in silico methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for acid lipase genes and encoded proteins using data from several mammalian genome projects. Mammalian acid lipase genes were located within a gene cluster for each of the 8 mammalian genomes examined, including human (Homo sapiens), chimpanzee (Pons troglodytes), rhesus monkey (Macacca mulatta), mouse (Mus musculus), rat (Rattus norvegicus), cow (Bos taurus), horse (Equus caballus) and dog (Canis familaris), with each containing 9 coding exons. Human and mouse acid lipases shared 44-87% sequence identity and exhibited sequence alignments and identities for key amino acid residues and conservation of predicted secondary and tertiary structures with those previously reported for human gastric lipase (LIPF) (Roussel et al., 1999). Evidence for a new family of acid lipase genes is reported for mouse and rat genomes, designated as Lipo. Mouse acid lipase genes are subject to differential mRNA tissue expression, with Lipa showing wide tissue expression, while others have a more restricted tissue expression in the digestive tract (Lipf), salivary gland (Lipo) and epidermal tissues (Lipk, Lipm and Lipn). Phylogenetic analyses of the mammalian acid lipase gene families suggested that these genes are products of gene duplication events prior to eutherian mammalian evolution and derived from an ancestral vertebrate LIPA gene, which is present in the frog, Xenopus tropicalis. Title: Mammalian carboxylesterase 3: comparative genomics and proteomics Holmes RS, Cox LA, Vandeberg JL Ref: Genetica, 138:695, 2010 : PubMed ESTHER: Holmes_2010_Genetica_138_695 PubMedSearch: Holmes 2010 Genetica 138 695 PubMedID: 20422440 Gene_locus related to this paper: human-CES3 Abstract 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. Title: Recommended nomenclature for five mammalian carboxylesterase gene families: human, mouse, and rat genes and proteins Holmes RS, Wright MW, Laulederkind SJ, Cox LA, Hosokawa M, Imai T, Ishibashi S, Lehner R, Miyazaki M and Maltais LJ <9 more author(s)> Holmes RS, Wright MW, Laulederkind SJ, Cox LA, Hosokawa M, Imai T, Ishibashi S, Lehner R, Miyazaki M, Perkins EJ, Potter PM, Redinbo MR, Robert J, Satoh T, Yamashita T, Yan B, Yokoi T, Zechner R, Maltais LJ (- 9) Ref: Mamm Genome, 21:427, 2010 : PubMed ESTHER: Holmes_2010_Mamm.Genome_21_427 PubMedSearch: Holmes 2010 Mamm.Genome 21 427 PubMedID: 20931200 Gene_locus related to this paper: human-CES1, human-CES2, human-CES3, human-CES4A, human-CES5A 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. Title: Baboon carboxylesterases 1 and 2: sequences, structures and phylogenetic relationships with human and other primate carboxylesterases Holmes RS, Glenn JP, Vandeberg JL, Cox LA Ref: J Med Primatol, 38:27, 2009 : PubMed ESTHER: Holmes_2009_J.Med.Primatol_38_27 PubMedSearch: Holmes 2009 J.Med.Primatol 38 27 PubMedID: 19187434 Gene_locus related to this paper: papha-b5tz25, papha-b5tz26 Abstract Background Carboxylesterase (CES) is predominantly responsible for the detoxification of a wide range of drugs and narcotics, and catalyze several reactions in cholesterol and fatty acid metabolism. Studies of the genetic and biochemical properties of primate CES may contribute to an improved understanding of human disease, including atherosclerosis, obesity and drug addiction, for which non-human primates serve as useful animal models. Title: Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor Holmes RS, Chan J, Cox LA, Murphy WJ, Vandeberg JL Ref: BMC Evol Biol, 8:54, 2008 : PubMed ESTHER: Holmes_2008_BMC.Evol.Biol_8_54 PubMedSearch: Holmes 2008 BMC.Evol.Biol 8 54 PubMedID: 18289373 Gene_locus related to this paper: mondo-b2bsf5, mondo-b2bsz5 Abstract BACKGROUND: Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution. Title: Mammalian carboxylesterase 5: comparative biochemistry and genomics Holmes RS, Cox LA, Vandeberg JL Ref: Comparative Biochemistry & Physiology Part D Genomics Proteomics, 3:195, 2008 : PubMed ESTHER: Holmes_2008_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_3_195 PubMedSearch: Holmes 2008 Comp.Biochem.Physiol.Part.D.Genomics.Proteomics 3 195 PubMedID: 19727319 Gene_locus related to this paper: bovin-e1bn79, canfa-cauxin, felca-CAUXIN, human-CES5A, mouse-cauxin, ratno-cauxin, sheep-cauxin Abstract Carboxylesterase 5 (CES5) (also called cauxin or CES7) is one of at least five mammalian CES gene families encoding enzymes of broad substrate specificity and catalysing hydrolytic and transesterification reactions. In silico methods were used to predict the amino acid sequences, secondary structures and gene locations for CES5 genes and gene products. Amino acid sequence alignments of mammalian CES5 enzymes enabled identification of key CES sequences previously reported for human CES1, as well as other sequences that are specific to the CES5 gene family, which were consistent with being monomeric in subunit structure and available for secretion into body fluids. Predicted secondary structures for mammalian CES5 demonstrated significant conservation with human CES1 as well as distinctive mammalian CES5 like structures. Mammalian CES5 genes are located in tandem with the CES1 gene(s), are transcribed on the reverse strand and contained 13 exons. CES5 has been previously reported in high concentrations in the urine (cauxin) of adult male cats, and within a protein complex of mammalian male epididymal fluids. Roles for CES5 may include regulating urinary levels of male cat pheromones; catalysing lipid transfer reactions within mammalian male reproductive fluids; and protecting neural tissue from drugs and xenobiotics. Title: Identification of promoter variants in baboon endothelial lipase that regulate high-density lipoprotein cholesterol levels Cox LA, Birnbaum S, Mahaney MC, Rainwater DL, Williams JT, Vandeberg JL Ref: Circulation, 116:1185, 2007 : PubMed ESTHER: Cox_2007_Circulation_116_1185 PubMedSearch: Cox 2007 Circulation 116 1185 PubMedID: 17709635 Gene_locus related to this paper: papha-a7ld44 Abstract BACKGROUND: High-density lipoprotein cholesterol (HDL) levels are a major risk factor for cardiovascular disease. Previously we identified a quantitative trait locus on baboon chromosome 18 that regulates HDL. From positional cloning studies and expression studies, we identified the endothelial lipase gene (LIPG) as the primary candidate gene for the quantitative trait locus. The mechanism by which LIPG variation influences HDL levels has not been determined. METHODS AND Title: Determinants of variation in serum paraoxonase enzyme activity in baboons Rainwater DL, Mahaney MC, Wang XL, Rogers J, Cox LA, Vandeberg JL Ref: J Lipid Res, 46:1450, 2005 : PubMed ESTHER: Rainwater_2005_J.Lipid.Res_46_1450 PubMedSearch: Rainwater 2005 J.Lipid.Res 46 1450 PubMedID: 15834129 Abstract Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 x 10(-8) and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53% of total trait variation in baboons is explained by genes and 17% by covariates, thus accounting for approximately 70% of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis. | |||||||
|
