Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of the spatial structure of ascorbate oxidase [Messerschmidt, A., Rossi, A., Ladenstein, R., Huber, R., Bolognesi, M., Gatti, G., Marchesini, A., Petruzzelli, R. & Finazzi-Agro, A. (1989) J. Mol. Biol. 206, 513-529], an alignment of the amino acid sequence of the related blue oxidases, laccase and ceruloplasmin is proposed. This strongly suggests a three-domain structure for laccase closely related to ascorbate oxidase and a six-domain structure of ceruloplasmin. These domains demonstrate homology with the small blue copper proteins. The relationships suggest that laccase, like ascorbate oxidase, has a mononuclear blue copper in domain 3 and a trinuclear copper between domain 1 and 3 and ceruloplasmin has mononuclear copper ions in domains 2, 4 and 6 and a trinuclear copper between domains 1 and 6.
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PMID:The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships. 240 64

Previous experiments showed that the presence of high levels of acute phase reactants (APR) enhance CCl4-induced liver fibrosis in the rat. A high correlation was found between the degree of fibrosis and alpha 2-macroglobulin of the rat (alpha 2-macrofetoprotein, alpha M-FP) used for monitoring the acute phase response. This acute phase reaction was provoked by epinephrine just before CCl4 treatment was started. In the present study we analyzed the effect of APR by repeating these experiments and estimating liver neutral collagenase with a synthetic substrate and endogenous collagen as a substrate, and liver prolyl-4-hydroxylase. A strong depression of liver collagenase activity was found in rats with a preceding acute phase reaction contrary to the rats that underwent CCl4 treatment only. A high level of alpha M-FP correlated negatively with collagenase activity. Also in vitro alpha M-FP proved to inhibit collagenase activity. Prolyl-4-hydroxylase was increased in the rats during acute phase reaction and correlated highly and positively with alpha M-FP, haptoglobin, and ceruloplasmin. Thus high levels of APR promote development of CCl4-induced fibrosis, partly by anticollagenase activity and partly because of enhancement of prolyl-4-hydroxylase activity. The latter phenomenon can also be explained by the presence of APR, but this has to be proved.
Exp Mol Pathol 1986 Oct
PMID:Mechanisms by which acute phase proteins enhance development of liver fibrosis: effects on collagenase and prolyl-4-hydroxylase activity in the rat liver. 242 60

To investigate our earlier hypothesis that carbohydrates play a regulatory role in the intracellular transport of secretory glycoproteins, we used 1-deoxynojirimycin (DNJ), and inhibitor of glucosidase I and II of the rough endoplasmic reticulum (RER), to modify the structure of N-linked glycan moieties of secretory glycoproteins of human hepatoma (Hep G2) cells in culture. Using a pulse-chase protocol, we found that treatment of Hep G2 cultures with 1.25 mM DNJ markedly reduced the rate of secretion of alpha 1-protease inhibitor, ceruloplasmin, and alpha 2-macroglobulin, but had no effect on the export of fibronectin, alpha-fetoprotein and transferrin, nor on albumin which lacks carbohydrate. For example, 50% of newly synthesized alpha 1-protease inhibitor, the glycoprotein most dramatically affected, was secreted by 27 min in control cultures versus 110 min in DNJ-treated cultures. Percoll gradient cell fractionation analyses revealed that DNJ inhibited transport of the affected secretory glycoproteins in the RER segment of the ER/Golgi pathway. For example, 50% of newly synthesized alpha 1-protease inhibitor was lost from the RER fraction by 10 min in untreated cells, but 70 min was required for the transport of a similar amount of protein in DNJ-treated cells. DNJ treatment also inhibited the rate at which the N-linked glycan moieties of the affected glycoproteins became resistant to endo H in the Golgi. Since the glycan moiety of secreted forms of the affected glycoproteins were fully processed to the complex structure, suggesting escape from DNJ inhibition, we concluded that removal of terminal glucose residues from the glycan chain of secretory glycoproteins is required for their transport from the RER to the Golgi. We suggest that the oligosaccharide moieties on alpha 1-protease inhibitor, ceruloplasmin and alpha 2-macroglobulin form part of the binding site for a receptor which regulates transport of these glycoproteins.
Mol Cell Biochem
PMID:Differential effects of 1-deoxynojirimycin on the intracellular transport of secretory glycoproteins of human hepatoma cells in culture. 243 31

Eight liver biopsy specimens from five patients with PAS-negative intracisternal hyalin were investigated by immunofluorescence for: (1) immunoglobulins (Ig) G, A, M, D, E; (2) light chains (kappa and lambda); (3) complement components C1q, C4, C3c, C5, C9; (4) C1-inactivator; (5) C3-activator; (6) alpha 1-antitrypsin; (7) alpha 1-antichymotrypsin; (8) plasminogen; (9) fibrinogen; (10) fibrinogen breakdown products D and E; (11) fibronectin; (12) prealbumin; (13) albumin; (14) betalipoprotein; (15) apolipoprotein; (16) alpha 1- and alpha 2-glycoprotein; (17) cholinesterase; (18) ceruloplasmin; (19) haemopexin; (20) myoglobin; (21) placenta lactogen; (22) transferrin; (23) actin; (24) myosin; (25) cathepsin D; and (26) hepatitis B surface and core antigens (HBsAg and HBcAg). The globules reacted significantly with antisera against C3c (three patients), C4 (three patients), C3-activator (one patient) and fibrinogen (two patients). The cause of the protein accumulation is not clear. Serial studies indicate the possibility of a disturbance of protein secretion and an as yet unidentified immune complex disorder.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Immunohistological investigations of PAS-negative globular intracisternal hyalin in human liver biopsy specimens. 285 88

Three clones carrying the sequences of ceruloplasmin gene were isolated from the library of EcoRI fragments of rat chromosomal DNA cloned in Charon 4A vector. These clones were identified using, i) plaque hybridization with [32P] cDNA transcribed from highly purified rat ceruloplasmin (Cp) mRNA; ii) blot hybridization of the restriction fragments of recombinant DNAs with Cp cDNA and iii) hybridization selection of Cp mRNA followed by its cell-free translation. Oligo (dT)-primed cDNA transcripts of Cp mRNA having different length as well as cloned Cp cDNA isolated from rat liver cDNA library were used as hybridization probes for the study of mRNA-coding segments of Cp gene. The length of inserts in recombinant DNAs varied from 7.5 up to 12.3 megadaltons. EcoRI-fragments of Cp gene were mapped within recombinant DNA and their homology to each other was studied.
Mol Biol (Mosk)
PMID:[Comparative analysis of recombinant bacteriophages containing the sequences of the chromosomal ceruloplasmin gene in the rat]. 298 69

The gene for human prothrombin, or factor II (F2) has been assigned to 11p11-q12 by the combined use of a panel of somatic cell hybrid DNAs and in situ hybridization, using both cDNA and genomic probes. In addition, the cDNA probe for F2 recognizes a homologous sequence which has been tentatively mapped to the X chromosome. Similar approaches have been used to confirm the assignment of the ceruloplasmin gene, but to regionally localize it more proximally than previously reported (3q21-q24). These results provide further evidence that genes encoding the coagulation factors and related proteins are dispersed throughout the human genome.
Somat Cell Mol Genet 1987 May
PMID:Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively. 347 86

Distribution of the transcriptionally active sequences in rat liver chromatin DNA fragments released from chromatin sites with different sensitivity to endogenous Ca2+, Mg2+-DNases was studied by the dot hybridization method with cloned DNA-probes. The internal fragment of the rat chromosomal ceruloplasmin gene containing coding sequences and the promoter region of the metallothionein-I gene were specific probes for the transcriptionally active liver chromatin. cDNA of beta-globin gene was the control for the transcriptionally inert DNA sequences. Mononucleosomal length, DNA (175-215 bp) formed in the course of mile nuclease digestion (less than 1% mononucleosomes and acid-soluble material) was 3-6-fold enriched in transcribed sequences of the ceruloplasmin gene as compared to oligonucleosomal DNA fragments produced in the same digestion conditions (fractions containing fragments 750-850 and greater than 2000 bp). The relative amount of the ceruloplasmin gene in mononucleosomal length DNA formed during the mild digestion was 12-25-fold greater than in total rat liver DNA and 25-50-fold greater than in the mononucleosomal DNA (150-175 bp) produced in the course of extensive digestion (80-85% mononucleosomes and 15-20% acid-soluble material) by endogenous Ca2+, Mg2+-DNases. The promoter metallothionein-I gene sequences exhibited the same distribution among chromatin fragments as the coding ceruloplasmin gene sequence. Distribution of the nontranscribed beta-globin sequences in liver chromatin DNA fragments produced at different stages of nuclease digestion was not related to chromatin sensitivity to endogenous DNases. These sequences were distributed similarly in different DNA size classes and total DNA.
Mol Biol (Mosk)
PMID:[Distribution of transcription-active DNA sequences in rat liver chromatin during fragmentation with endogenous DNAses]. 357 99

The identification of possible copper ligands in human ceruloplasmin was carried out by the computer similarity analysis for sequences of ceruloplasmin and several other copper oxidases: azurin, plastocyanin, superoxide dismutase, tyrosinase and hemocyanin. It follows from the analysis of inter- and intramolecular homology that copper active sites of different types appeared to be in close contacts within the ceruloplasmin molecule.
Mol Biol (Mosk)
PMID:[Localization of active sites in human ceruloplasmin from data of intra- and intermolecular homology]. 365 83

The distribution of the sequences coding for ceruloplasmin (CP) in rat liver heterogeneous nuclear RNA (hnRNA) was studied using highly specific CP cDNA as a hybridization probe. The content of CP-coding sequences in poly(A)-containing and poly(A)-free subfractions of hnRNA was shown to be respectively 1 and 27 equivalents of CP mRNA molecule per one hepatocyte. The gel electrophoresis of hnRNA under strongly denaturing conditions with the subsequent transfer of RNA to diazobenzyloxymethyl paper and hybridization with [32P]-cDNA probe showed that CP mRNA sequences were of multiple molecular weight distribution. In particular, 9.0, 6.6, 2.4 and 1.6 megadalton fractions of non-polyadenylate hnRNA carried CP-coding sequences while the only hand that hybridized to CP cDNA was detected in polyadenylated hnRNA. This band was of a molecular weight 1.1-1.2 megadaltons corresponding to that of cytoplasmic CP mRNA. The hybridization of high molecular weight hnRNA with full-length CP cDNA followed by the determination of the size of cDNA fragments protected against SI nuclease demonstrated that coding sequences of CP pre-mRNA are interrupted by intervening sequences.
Mol Biol (Mosk)
PMID:[Nuclear precursors for ceruloplasmin-coding messenger RNA from rat liver]. 616 2

Distribution of ceruloplasmin-coding sequences among fragments of rat nuclear DNA obtained after complete cleavage with seven restriction endonucleases was studied using highly specific complementary DNA probes. Three different procedures were used for the synthesis of cDNAs, whose relative advantages and disadvantages are discussed in this work. The number of restriction fragments carrying ceruloplasmin gene sequences varied from two to five depending on the enzyme used. The total molecular weight of these fragments was several times higher than the minimal length of ceruloplasmin structural gene deduced from the molecular size of mRNA. The restriction endonuclease cleavage of the partial double-stranded transcript of ceruloplasmin mRNA coding for about 60% of its length from the 3'-end has shown that distribution of restriction endonuclease cleavage sites on the dsDNA differs in the position of cleavage sites on the ceruloplasmin gene in cellular DNA. Hybridization of cDNA with total cellular DNA allows to determine 1.3-1.4 copies of ceruloplasmin gene in the rat haploid genome. Proceeding from the data obtained it may be stated that the rat ceruloplasmin gene is constructed of several structural gene segments cut by introns.
Mol Biol (Mosk)
PMID:[Structural organization of rat ceruloplasmin gene]. 626 65


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