Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The malate-aspartate shuttle, consisting of mitochondrial and cytosolic aspartate aminotransferase and mitochondrial and cytosolic malate dehydrogenase, is a major pathway for the transport of reducing equivalents from cytosol to mitochondria in mammals. To elucidate molecular mechanisms regulating metabolic coordination between the mitochondria and the cytosol, we analyzed the 5'-flanking regulatory regions of the complete set of mouse isoenzyme genes playing a pivotal role in the shuttle. Deletion analysis and an in vivo transfection assay, using NIH3T3 cells, revealed that all the promoter regions are located within the 300-base pair regions upstream from the initiation codon. Subsequently, DNase I footprinting analyses using NIH3T3 cell nuclear extracts led to identification of several protein binding sites within these promoter regions. A synthetic oligomer containing the consensus binding site sequence for CTF/NFI, a transcription factor for RNA polymerase II, competed for the binding of proteins to the promoter regions of cytosolic aspartate aminotransferase and mitochondrial and cytosolic malate dehydrogenase genes, but not for that of the mitochondrial aspartate amino-transferase gene. On the other hand, a synthetic oligomer containing the consensus binding site sequence for Sp1, which activates transcription from promoters containing properly positioned GC boxes, competed for protein(s) binding to the promoter region of the mitochondrial aspartate aminotransferase gene.
 ...
PMID:Regulatory regions of the mitochondrial and cytosolic isoenzyme genes participating in the malate-aspartate shuttle. 229 30

Structural organization of the entire mouse mitochondrial aspartate aminotransferase (EC 2.6.1.1) gene was determined by analyzing the overlapping genomic clones obtained from a Charon 4A DNA library. The gene is 25 X 10(3) base-pairs long and contains ten exons interrupted by nine introns of various sizes. The 5' and 3'-flanking regions, the exact sizes and boundaries of the exon blocks including the transcription-initiation sites were determined. The 5' end of the gene lacks the prototypical 5' transcriptional regulatory sequence elements, such as TATA and CAAT boxes, but contains G + C-rich sequences, two putative binding sites for a cellular transcription factor, Sp1, and multiple transcription-initiation sites. Moreover, the sequences around the transcription-initiation sites are compatible with the formation of a number of potentially stable stem-loop structures. The leader sequence, which is essential for the transport of the protein into the mitochondria, is coded by the first exon and is separated from the mature protein by the first intron. The pyridoxal 5'-phosphate-binding domain, consisting of seven alternating beta-sheets and alpha-helical polypeptide strands, is separated by four introns present at the ends of alpha-helices. These genomic DNA structures suggest that the introns were not inserted into a previously uninterrupted coding sequence, but rather are products of evolution of the ancestral gene. However, a further correlation between the positions of introns relative to the well-defined structural domains of the mature protein was not obvious.
 ...
PMID:Structural organization of the mouse mitochondrial aspartate aminotransferase gene. 282 32

Structural organization of the mouse mitochondrial malate dehydrogenase (EC 1.1.1.37) gene was determined by analyzing a genomic DNA fragment isolated from a cosmid library. The gene is 12,000 base-pairs long and contains nine exons interrupted by eight introns of various sizes. The 5' and 3'-flanking regions, and the exact sizes and boundaries of the exon blocks including the transcription-initiation sites were determined. In the 5'-flanking region, there is neither a TATA box nor a CAAT box. Instead of these sequences, there are six copies of the GGGCGG or CCGCCC sequence, which is a potential binding site for the transcription factor, Sp1. The 5'-flanking region up to about 600 nucleotides is G + C-rich (65%) and contains sequences compatible with the formation of a number of potentially stable stem-loop structures. S1 nuclease mapping and primer extension analysis demonstrated that transcription of the mitochondrial malate dehydrogenase gene initiates at multiple sites. Comparison of the nucleotide sequence of the promoter region of the mitochondrial malate dehydrogenase gene with that of the mitochondrial aspartate aminotransferase gene, revealed that there are several highly conserved regions between these two mitochondrial enzyme genes participating in the malate-aspartate shuttle.
 ...
PMID:Structural organization of the mouse mitochondrial malate dehydrogenase gene. 337 35

We have cloned and characterized a mouse cytosolic aspartate aminotransferase (AspAT) (EC 2.6.1.1) gene, which is about 32,000 base-pairs long and is interrupted by eight introns. The 5' and 3'-flanking regions, and the exact sizes and boundaries of the exon blocks, including the transcription-initiation sites, were determined. The 5' end of the gene lacks the TATA and CAAT boxes characteristic of eukaryotic promoters, but contains G + C-rich sequences, three putative binding sites for a cellular transcription factor, Sp1, and multiple transcription-initiation sites. The sequences around the transcription-initiation sites are compatible with the formation of a number of potentially stable stem-loop structures. We compared the structural organization of the mouse cytosolic AspAT gene with that of the mouse mitochondrial AspAT gene, which has nine introns. We found that the promoter regions share a high level of homology and five of the introns are at identical places. This close matching leads to the tentative conclusion that the introns were in place before the divergence of cytosolic and mitochondrial isoenzyme genes.
 ...
PMID:Structural organization of the mouse aspartate aminotransferase isoenzyme genes. Introns antedate the divergence of cytosolic and mitochondrial isoenzyme genes. 337 36

Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat-sen University between January 2018 and January 2020. HepG2.2.15 and HepG2-NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN-treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2-overexpressing or C2-silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT-qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV-DNA was measured by RT-qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti-virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38-MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.
 ...
PMID:Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients. 3238 93