Disease relevance of Got2

• Levels of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome proliferators, while levels in hepatoma cells were similar regardless of treatment [1].
• Mouse mammary tumor viruses (MMTVs) contain distinct membrane glycoproteins of 52,000 daltons (gp52) and 36,000 daltons (gp36) [2].

High impact information on Got2

• 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake [3].
• The overall increase in Vmax between pFR400 and pFR400/pMAAT2 in the presence of Zn2+ was 10.4-fold (P < 0.01) and was highly correlated (r = 0.99) with expression of FABPpm in plasma membranes as determined by Western blotting [3].
• Leptin may normally down-regulate expression of plasma membrane fatty acid binding protein [4].
• The uptake of FA across the plasma membrane may be mediated by three distinct proteins--FA translocase (FAT), plasma membrane FA binding protein (FABP-pm), and FA transport protein (FATP)--that have recently been characterized [5].
• Adipocyte differentiation of 3T3-L1 cells involves augmented expression of a 43-kDa plasma membrane fatty acid-binding protein [6].

Biological context of Got2

• The nucleotide sequences of mRNAs for the mouse mitochondrial and cytosolic aspartate aminotransferase isoenzymes (mAspAT and cAspAT) (EC 2.6.1.1) were determined from complementary DNAs [7].
• 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 [8].
• Mitochondrial aspartate aminotransferase: direction of a single protein with two distinct functions to two subcellular sites does not require alternative splicing of the mRNA [9].
• 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 [10].
• The deduced amino acid sequences of mouse cAspAT and mAspAT showed about 47%, and those of mouse cMDH and mMDH, about 23% overall homology [11].

Anatomical context of Got2

• FABP-pm mRNA levels were twofold higher in liver and 50% higher in adipose tissue of ob/ob mice [5].
• The additional exon for the N-terminal presequence that directs mitochondrial aspartate aminotransferase into the mitochondria is separated by the largest intron from the rest of the gene [12].
• Mitochondrial aspartate aminotransferase expressed on the surface of 3T3-L1 adipocytes mediates saturable fatty acid uptake [13].
• A plasma membrane fatty acid-binding protein (h-FABPpm) has been isolated from rat hepatocytes [14].

Associations of Got2 with chemical compounds

• The activities of malate-aspartate shuttle enzymes viz., cytosolic and mitochondrial aspartate aminotransferase (c- and m-AsAT) and malate dehydrogenase (c- and m-MDH) were measured in liver and kidney of ad libitum (AL) and dietary-restricted (DR) mice and also on triiodothyronine (T3) treatment [15].
• 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 [16].
• PLP-dependent mitochondrial aspartate aminotransferase (mitAspAT) is a mitochondrial enzyme that catalyzes beta-elimination reactions with cysteine S-conjugates of halogenated alkenes [17].
• Physicochemical studies have suggested that the 43-kDa plasma membrane fatty acid binding protein (FABPpm) is closely related to the mitochondrial isoform of aspartate aminotransferase (mAspAT) [13].
• As with anti-FABPpm, antibodies to mAspAT selectively inhibited the uptake of [3H]-oleate in 3T3-L1 adipocytes but not in fibroblasts, while having no effect on uptake of either 2-deoxyglucose or the medium chain fatty acid octanoate [13].

Physical interactions of Got2

• Identification of Hsc70 binding sites in mitochondrial aspartate aminotransferase [18].

Other interactions of Got2

• Differentiation, induced by high calcium, did not affect FATP mRNA levels, but resulted in an approximately 50% increase in FACS mRNA, while decreasing FABP-pm mRNA by 50% [19].
• The region coding for the mature mAspAT and that for the cAspAT show about 53% overall homology [7].
• Thus, for mAAT the discrimination between native and non-native structures by Hsc70 may rely more on the level of structure of the binding sites than on their degree of exposure to the solvent in the native structure [18].
• Three different nuclear loci for mitochondrial enzymes (Mod-2, Got-2, and Mor-1) have now been mapped in the mouse, all on different chromosomes [20].

Analytical, diagnostic and therapeutic context of Got2

• Neither untransfected 3T3 nor pFR400 cells expressed cell surface FABPpm detectable by immunofluorescence [3].
• We report here the development of new radioimmunoassays for gp36, using gp36 purified by hydrophobic chromatography and gel filtration [2].
• In the present studies, mAspAT was not detected immunohistochemically or by immunoblotting in plasma membranes of proliferating 3T3-L1 fibroblasts [13].
• Molecular cloning and in vivo expression of a precursor to rat mitochondrial aspartate aminotransferase [21].
• Monoclonal and polyclonal antibodies against porcine mitochondrial aspartate aminotransferase: their inhibition modes and application to enzyme immunoassay [22].

References