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Originally published In Press as doi:10.1074/jbc.M006753200 on August 23, 2000

J. Biol. Chem., Vol. 275, Issue 50, 39543-39554, December 15, 2000
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Aspartyl beta -Hydroxylase (Asph) and an Evolutionarily Conserved Isoform of Asph Missing the Catalytic Domain Share Exons with Junctin*

Joseph E. DinchukDagger §, Nancy L. HendersonDagger , Timothy C. BurnDagger , Reid HuberDagger , Siew Peng Ho, John LinkDagger , Karyn T O'NeilDagger , Richard J. FochtDagger , Michael S. Scully, Jeannine M. HollisDagger , Gregory F. HollisDagger , and Paul A. Friedman||

From the Dagger  Department of Applied Biotechnology, the  Department of Central Nervous System Diseases Research, and || DuPont Pharmaceuticals Research Laboratories, DuPont Pharmaceuticals Company, Experimental Station, Wilmington, Delaware 19880

The mouse aspartyl beta -hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. Monoclonal antibody reagents were generated, epitope-mapped, and used to definitively correlate RNA bands on Northern blots with protein species on Western blots. The gene for mouse junctin, a calsequestrin-binding protein, was cloned and characterized and shown to be encoded from the same locus. When expressed in heart tissue, BAH/humbug preferably use the first exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading frames and use separate promoters to achieve differential expression, splicing, and function in a variety of tissues. This unusual form of exon sharing suggests that the functions of junctin, BAH, and humbug may be linked.


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF289199, AF289200, AF289205-AF289215, and AF289486-AF289494.

§ To whom correspondence should be addressed: Dept. of Applied Biotechnology, Experimental Station, E400/5446, Wilmington, DE 19880-0400. Tel.: 302-695-9180; Fax: 302-695-9401; E-mail: joseph.e.dinchuk@dupontpharma.com.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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