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Human ceruloplasmin gene and cDNA Wager, William R.


Ceruloplasmin is a 132Kda serum protein found in all vetebrates. The protein ismulti-functional. Functions include copper transport, serum and tissue anti-oxidant and anti-coagulation modulation. The cDNA of ceruloplasmin sharehomology with the cDNAs of factors V and VIII of the blood coagulation cascade,suggesting that the three genes evolved from a common ancestral gene. Thereare two ceruloplasmin specific mRNA transcripts, 3.7 and 4.4 Kb, produced bythe liver. Expression of the gene is regulated transcriptionally and post-transcriptionally. The initial aim of this study was to isolate the 3' end of the gene and todetermine the evolutionary relationship with the factor V and VIII genes.Further aims were to isolate and characterize the 5' and 3' ends of the cDNA inorder to determine their role in the regulation of gene expression. The gene for human ceruloplasmin is 38 Kbp in length and is composed of atleast 19 exons separated by 18 introns. The exact number of 5' and 3'untranslated exons is unclear at the present. The gene structure of ceruloplasminshares homology with the genes for factor V and VIII. The 4 amino acid additionreported by Yang et al., (1986) is produced by use of an alternate splice junctionat the 3' end of exon 18. A 5' cDNA clone that contained 114 by prior to theinitiator methionine was isolated. The clone is produced by splicing of theprimary heteronuclear transcript. The origin of the 5' end of the clone isunmapped at the present. A series of 3' cDNA clones was isolated. All the clonesencode the COOH-terminus of the protein, but differ from the 3' genomicsequence at points beyond the stop codon. The clones diverge from the genomicsequence at splice junction consensus site. The origin of the 3' untranslated sequence is unmapped at the present. One 3'clone hybridizes only to the 4.4 Kb transcript. The ceruloplasmin gene probably diverged from the ancestral gene before thedivergence of the genes for factor V and VIII. The two different length mRNAtranscripts are a result of both 5' and 3' untranslated sequence additions to thecoding mRNA. The role of these untranslated sequences in regulation ofceruloplasmin gene expression is unclear at the present.

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