ISOLATION, CHARACTERIZATION AND STRUCTURAL ORGANIZATION OF THE GENE AND PSEUDOGENE FOR THE DIHYDROLIPOAMIDE SUCCINYLTRANSFERASE COMPONENT OF THE HUMAN 2-OXOGLUTARATE DEHYDROGENASE COMPLEX
K. Nakano et al., ISOLATION, CHARACTERIZATION AND STRUCTURAL ORGANIZATION OF THE GENE AND PSEUDOGENE FOR THE DIHYDROLIPOAMIDE SUCCINYLTRANSFERASE COMPONENT OF THE HUMAN 2-OXOGLUTARATE DEHYDROGENASE COMPLEX, European journal of biochemistry, 224(1), 1994, pp. 179-189
In the present study, the dihydrolipoamide succinyltransferase gene of
the 2-oxoglutarate dehydrogenase complex was isolated from a human ge
nomic DNA library and its entire nucleotide sequence was determined. T
his gene was approximately 23 kbp in size with 15 exons and 14 introns
. All of the donor and acceptor splice sites of this gene conformed to
the GT/AG rule. A quanine residue 43 bases upstreams of the ATG initi
ating translation codon was the transcription initiation site of the h
uman dihydrolipoamide succinyltransferase mRNA. Sequence analysis of t
he promoter-regulatory region showed the presence of a CAAT-box-like s
equence but the presence of a TATA-box-like sequence was not evidenced
. Also located in this region were sequences resembling glucocorticoid
-responsive and cAMP-responsive elements, and an Sp1 binding site. No
nucleotide sequence corresponding to the E3-binding and/or E1-binding
domain was found in any region of the gene. Therefore, the exon coding
for the E3-binding and/or E1-binding domain may have been lost from t
he gene during evolution. Moreover, a processed pseudogene of dihydrol
ipoamide succinyltransferase was isolated and sequenced. The nucleotid
e sequence of the pseudogene is 93% similar to the sequence of the hum
an dihydrolipoamide succinyltransferase cDNA, but the pseudogene is no
t functional for base changes, deletions and insertions of the pseudog
ene. Southern-blot analysis showed the presence of a single copy of th
is gene and a single copy of a pseudogene in the human genome. In addi
tion, a possible relationship between dihydrolipoamide succinyltransfe
rase and familial Alzheimer's disease is discussed.