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