Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysyl oxidase (protein-lysine 6-oxidase; EC 1.4.3.13) is a copper-containing enzyme that functions extracellularly and catalyses the oxidative deamination of peptidyl lysine. Lysyl oxidase was purified 150-175-fold from urea extracts of rat skin and uteri. Features of the enzyme were similar to those reported previously for lysyl oxidase obtained from rat aorta and bovine ligamenture. However, both approximately 40 and approximately 32 kDa polypeptide chains could be isolated from rat skin with apparent lysyl oxidase activity. Antibodies raised in chickens against the approximately 40 kDa form of lysyl oxidase detected the approximately 32 kDa form in immunoblots. Consequently it is inferred that the approximately 32 kDa form of lysyl oxidase is processed from the approximately 40 kDa form of the enzyme. The antibodies were also used to prepare anti(rat lysyl oxidase) affinity columns to facilitate the separation of lysyl oxidase from other proteins in studies to assess the extent to which lysyl oxidase serves as a reservoir for skin copper. At 16 h after an oral dose of copper, as 67Cu, about 6-8% of the total 67Cu incorporated into rat skin was found in association with lysyl oxidase. The lysyl oxidase concentration in rat skin was 2.5-7.5 nmol/g (determined by e.l.i.s.a.). Changing the copper status of rats by feeding a diet deficient in copper did not appear to influence lysyl oxidase accumulation in skin nor the percentage of incorporation of 67Cu in skin as lysyl oxidase. However, when rats were deprived of copper, the functional activity of lysyl oxidase in skin was one-third to one-half the normal values.
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PMID:Purification, properties and influence of dietary copper on accumulation and functional activity of lysyl oxidase in rat skin. 167 61

Lysyl oxidase (EC 1.4.3.13) initiates the crosslinking of collagens and elastin by catalyzing oxidative deamination of the epsilon-amino group in certain lysine and hydroxylysine residues. We report here on the isolation and characterization of cDNA clones for the enzyme from human placenta and rat aorta lambda gt11 cDNA libraries. A cDNA clone for human lysyl oxidase covers all the coding sequences, 230 nucleotides of the 5' and 299 nucleotides, of the 3' untranslated sequences, including a poly(A) tail of 23 nucleotides. This cDNA encodes a polypeptide of 417 amino acid residues, including a signal peptide of 21 amino acids. Sequencing of two rat lysyl oxidase cDNA clones indicated six differences between the present and the previously published sequence for the rat enzyme [Trackman et al. (1990) Biochemistry 29: 4863-4870], resulting in frameshifts in the translated sequence. The human lysyl oxidase sequence was found to be 78% identical to the revised rat sequence at the nucleotide level and 84% identical at the amino acid level, with the degree of identity unevenly distributed between various regions of the coded polypeptide. Northern blot analysis of human skin fibroblasts RNA indicated that the human lysyl oxidase cDNA hybridizes to at least four mRNA species; their sizes are about 5.5, 4.3, 2.4, and 2.0 kb. Analysis of a panel of 25 human x hamster cell hybrids by Southern blotting mapped the human lysyl oxidase gene to chromosome 5, and in situ hybridization mapped it to 5q23.3-31.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular cloning of human lysyl oxidase and assignment of the gene to chromosome 5q23.3-31.2. 168 72

Lysyl oxidase cDNA clones were identified by their reactivity with anti-bovine lysyl oxidase in a neonatal rat aorta cDNA lambda gt11 expression library. A 500-bp cDNA sequence encoding four of six peptides derived from proteolytic digests of bovine aorta lysyl oxidase was found from the overlapping cDNA sequences of two positive clones. The library was rescreened with a radiolabeled cDNA probe made from one of these clones, thus identifying an additional 13 positive clones. Sequencing of the largest two of these overlapping clones resulted in 2672 bp of cDNA sequence containing partial 5'- and 3'-untranslated sequences of 286 and 1159 nucleotides, respectively, and a complete open reading frame of 1227 bp encoding a polypeptide of 409 amino acids (46 kDa), consistent with the 48 +/- 3 kDa cell-free translation product of rat smooth muscle cell RNA that was immunoprecipitated by anti-bovine lysyl oxidase. The rat aorta cDNA-derived amino acid sequence contains the sequence of each of the six peptides isolated and sequenced from the 32-kDa bovine aorta enzyme, including the C-terminal peptide with sequence identity of 96%. Northern blots screened with lysyl oxidase cDNA probes identified hybridizing species of 5.8 and 4.5 kb in mRNA of rat aorta and lung, while dot blot analyses were negative for lysyl oxidase mRNA in preparations of rat brain, liver, kidney, and heart. A 258-bp segment of the 3'-untranslated region of lysyl oxidase cDNA is 93% identical with a highly conserved region of the 3'-untranslated sequence of rat elastin cDNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning of rat aorta lysyl oxidase cDNA: complete codons and predicted amino acid sequence. 167 81

Using Western immunoblotting, the extractable proteins of the bovine zonular fibers were examined for reactivity with two zonular antisera known to have strong affinity for zonular fibers in tissues, in order to identify the antigenic components. The extracts were also tested with antisera to several matrix proteins that have been reported to be associated with zonular fibers. Proteins reactive with antisera to bovine serum albumin, serum immunoglobulins and fibronectin were present. No bands reactive with antisera to a-elastin, prealbumin, amyloid P component, collagen VI, lysyl oxidase or monoclonal antibody to fibrillin were demonstrated. The major nonserum protein band identified by both antisera was a 32kD polypeptide. An equally strong 250kD polypeptide was shown by the antiserum to guanidine-dithiothreitol extracted zonular fibers. Both of these proteins were PAS-positive and were demonstrated also by the antisera in extracts of bovine elastic neck ligament. Whether the two glycoproteins are related to each other, with the higher molecular weight protein either a precursor or aggregate form, is not yet clear. They appear to bear a close relationship to the elusive core microfibrillar protein.
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PMID:Identification of extractable proteins from the bovine ocular zonule: major zonular antigens of 32kD and 250kD. 337 Oct 65

The oxidation of an elastin substrate by highly purified bovine aortic lysyl oxidase (LO) is markedly influenced by amphiphilic molecules known to bind to elastin. Negatively charged elastin ligands, including fatty acids, bile salts or sodium dodecyl sulfate can completely inhibit the oxidation of lysine in elastin, the cationic amphiphilic ligands stimulate the enzymatic reaction five-fold, while small hydrophilic molecules of either charge or neutral detergents have no effect. In addition, evidence has been obtained that changes in the conformation of a synthetic polypeptide substrate markedly alter its susceptibility to LO. The coacervated state of the substrate is most readily oxidized and crosslinked by the enzyme. These results point to the importance of small ligands, electrostatic charge, and conformation as substrate-directed influences which can control the expression of LO activity.
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PMID:Substrate-directed modulation of elastin oxidation by lysyl oxidase. 611 10

The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be comprised of two distinct components, a more abundant amorphous component and the microfibrillar component. The microfibrillar component is found in 10- to 12-nm fibrils which are located primarily around the periphery of the amorphous component but, to some extent, interspersed within it. The protein, elastin, makes up the highly insoluble amorphous component and is responsible for the elastic properties. Elastin is found throughout the vertebrate kingdom except for very primitive fish and possesses an unusual chemical composition consonant with its characteristic physical properties. Elastin is composed largely of glycine, proline, and other hydrophobic residues and contains multiple lysine-derived cross-links, such as the desmosines, which link the individual polypeptide chains into a rubber-like network. The intervening, hydrophobic regions of the polypeptide chains between the cross-links are highly mobile, and the elastic properties of the fibers can be described in terms of the theory of rubber elasticity. Recent application of recombinant DNA techniques has led to further understanding of the structure of elastin. Analyses of the bovine and human elastin genes have demonstrated that the hydrophobic and cross-linking domains are encoded in separate exons. These exons tend to be small, varying from 27 to 114 base pairs, and are separated by large intervening sequences. Furthermore, DNA sequence analysis has demonstrated that the elastin molecule contains two cysteine residues which were not previously identified near the carboxy terminus and which may be important in the interaction of elastin with other extracellular matrix proteins. Further DNA sequencing should determine the complete amino acid sequence of elastin. Biosynthetic studies and in vitro translation of elastin mRNA have demonstrated that a 72,000-dalton polypeptide, designated tropoelastin, is the initial translation product. Analysis of several developing systems has demonstrated that elastin synthesis is controlled by the level of elastin mRNA. After packaging into membrane-bound vesicles in the Golgi apparatus, tropoelastin is secreted by exocytosis into the extracellular space where it is cross-linked by a copper-requiring extracellular enzyme, lysyl oxidase. Elastin can be solubilized only by proteases that have consequently been designated elastases, although these are general, powerful proteases that can hydrolyze numerous proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Elastin: relation of protein and gene structure to disease. 615 Jan 37

Elastic fibers are important for elasticity and extensibility of lung tissue. In the developing lung, elastic fibers appear in greatest numbers during the process or period of alveolarization . A variety of mesenchymal cells in lung appear responsible for elastin synthesis. Elastin is a novel protein both from the standpoint of its processing into elastic fibers and chemical properties. For example, elastin undergoes posttranslational modification before its assembly into fibers. These steps include limited proteolysis, hydroxylation of prolyl residues and the oxidative deamination of lysyl residues prior to their incorporation into the crosslinks that covalently bond together polypeptide chains of elastin. The crosslinking amino acids include lysinonorleucine , merodesmosine and desmosine isomers. A key enzyme that controls this process is lysyl oxidase. Lysyl oxidase is a copper metalloprotein whose activity is responsive to and modulated by environmental insults, nutrition deficiencies and the administration of various pharmacological agents. Regarding chemical properties, elastin is one of the most apolar proteins secreted by mammalian cells. Moreover, elastin is one of the most long-lived proteins secreted into the extracellular matrix. In relationship to its processing into elastic fibers and chemical properties, details related to major aspects of elastin metabolism as well as speculation on its potential as a factor in lung development and disease are discussed.
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PMID:Elastin metabolism and chemistry: potential roles in lung development and structure. 637 98

Enzymic hydrolysis, followed by amino acid analysis, provided no evidence for the presence of epsilon-(gamma-glutamyl) lysine or other isopeptide crosslinks in connectin. Gel elecrrophoresis in the presence of sodium dodecyl sulphate did not reveal any difference in connectin between normal and lathyritic muscle, indicating that lysyl oxidase does not initiate cross-link formation in connectin. Although connectin may be covalently crosslinked by some unknown mechanism, the available evidence suggests that the subunit of MW approximately to 900 000 is synthesised as a single polypeptide chain. In developing fetal muscle, myosin heavy chains are apparent some weeks earlier than connectin. This, together with the known susceptibility of connectin to hydrolysis, suggests that connectin exists in an exposed environment rather than as a core to the thick filament.
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PMID:Studies on the structure of connectin in muscle. 717 2

Transforming growth factor(TGF)beta 1 is a potent inhibitor of growth in mouse osteoblastic MC3T3-E1 cells. To isolate genes that are induced by TGF beta 1, the differential screening method was adopted using a cDNA library constructed from cells treated with TGF beta 1 for 4 h. Six independent cDNA clones were isolated (TGF beta-stimulated clone, TSC-5, TSC-36, TSC-115, TSC-128, TSC-160 and TSC-161), the expression of which was increased by TGF beta 1-treatment with maximal expression at 6-10 h. The steady-state levels of TSC-36, TSC-128 and TSC-160 increased almost tenfold, whereas those of TSC-5, TSC-115 and TSC-161 were elevated at most threefold. From partial nucleotide sequences, TSC-160 was found to be identical to rrg (ras-recision gene, lysyl oxidase), and TSC-115 had 80% similarity with tropomyosin cDNA, whereas other genes seemed novel. Expression of TSC-36 and TSC-160 was dramatically decreased in v-Ki-ras-transformed MC3T3 cells or in transformed NIH 3T3 cells (DT), and was recovered to normal levels in a flat revertant (C11). A nearly full-length copy of TSC-36 cDNA was isolated, and an open reading frame indicated that it encodes a protein of 35 kDa. An antiserum was raised against the C-terminal peptide predicted from the nucleotide sequence, and a polypeptide with an approximate molecular mass of 38 kDa was detected in cultured medium of MC3T3-E1 cells. The amino acid sequence of TSC-36 protein was found to have some similarity with follistatin, an activin-binding protein, and a limited similarity with the secreted protein rich in cysteine (SPARC).
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PMID:Cloning from a mouse osteoblastic cell line of a set of transforming-growth-factor-beta 1-regulated genes, one of which seems to encode a follistatin-related polypeptide. 790 Oct 4

Two independent clones from the genomic DNA of a marine sponge Microciona prolifera were isolated by hybridization to the Caenorhabditis elegans Col-1 gene and one clone was obtained from genomic DNA by PCR. They contain open reading frames (MpCol1, MpCol2, MpCol3, MpCol4) capable of coding for a family of collagens different from those previously found in sponges. Southern blotting of genomic DNA suggested the presence of several other homologous genes. cDNA clones covering most of the triple-helical coding domain and the 3' untranslated region of MpCol1 were isolated by specific primers and reverse PCR. Two cDNA clones end in the middle of an AATAAA sequence 170 bp downstream from the translation stop codon of MpCol1. The putative NH2-terminal noncollagenous peptide is composed of only seven amino acid residues. The 1074-bp triple-helical coding region is not interrupted by intervening sequences. It codes for a polypeptide of 120 Gly-Xaa-Yaa triplets with only one short interruption near the COOH terminus. A putative N-glycosylation sequence (Asn-Gly-Ser), three Arg-Gly-Asp triplets known as cell recognition peptides, frequent Lys residues in the Yaa position (which are templates for hydroxylation), several Lys-Gly-Asn/Xaa-Arg peptides known as the lysyl oxidase recognition site, and long stretches without imino acids could be found within the triple-helical domain. The short COOH-terminal noncollagenous domain closely resembles that of nematode cuticular collagens and vertebrate nonfibrillar collagens. Our results strongly support the idea that the diversity of collagen genes and gene families found in higher organisms already existed in sponge.
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PMID:Characterization of an intronless collagen gene family in the marine sponge Microciona prolifera. 834 46


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