Structure and expression of mouse aldolase genes. Brain-specific aldolase C amino acid sequence is closely related to aldolase A (original) (raw)
Related papers
European Journal of Biochemistry, 1988
The complete nucleotide sequence of the human aldolase A isoenzyme gene is reported. The cloned gene sequence, spanning 7530 bp, includes twelve exons and occurs as a single copy per haploid human genome. The structural organization of the gene is quite complex: eight exons containing the coding sequence are common to all mRNAs extracted from human and other mammalian sources; four additional exons are present in the 5' untranslated region, of these one is contained in the ubiquitous type of mRNA, the second is in the musclespecific type of mRNA and the third and fourth are in a minor species of mRNA found in human liver tissue. Furthermore, the determined sequence includes 1000 nucleotides upstream from the first exon (exon I) in the 5' flanking region, and 400 nucleotides, which include the polyadenylation signal, downstream from the termination codon.
The complete amino acid sequence of the human aldolase C isozyme derived from genomic clones
Biochimie, 1987
The complete protein sequence of the human aldolase C isozyme has been determined from recombinant genomic clones. A genomic fragment of 6673 base pairs was isolated and the DNA sequence determined. Aldolase protein sequences, being highly conserved, allowed the derivation of the sequence of this isozyme by comparison of open reading frames in the genomic DNA to the protein sequence of other human aldolase enzymes. The protein sequence of the third aldolase isozyme found in vertebrates, aldolase C, completes the primary structural determination for this family of isozymes. Overall, the aldolase C isozyme shared 81o70 amino acid homology with aldolase A and 70°?o homology with aldolase B. The comparisons with other aldolase isozymes revealed several aldolase C-specific residues which could be involved in its function in the brain. The data indicated that the gene structure of aldolase C is the same as other aldolase genes in birds and mammals, having nine exons sep~ated by eight introns, ~! in precisely the same positions, only the intron sizes being different. Eight of these exons contain the protein coding region comprised of 363 amino acids. The entire gene is approximately 4 kilobases.
Differential distribution of aldolase A and C in the human central nervous system
Journal of Neurocytology, 2001
We have analyzed the distribution of aldolase A and C mRNAs and proteins in various areas of the human brain using Northern blot analyses and immunohistochemistry. Aldolase A mRNA expression was higher than aldolase C mRNA expression in all areas of the brain examined. Aldolase C mRNA expression was highest in the cerebellum. Aldolase C protein was present in well-delimited
Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones
Proceedings of the National Academy of Sciences, 1984
Several aldolase B clones from a human liver cDNA library have been identified by using a rabbit aldolase A cDNA as a hybridization probe. The most complete of these, pHL413, is 1389 base pairs long and covers -80% of the length of the mRNA, including 90% of the translated region. The cDNA, pHL413, was used to identify a genomic clone, XHG313, which encoded the remaining amino acids of human aldolase B. We demonstrate that the amino acid and nucleotide sequences of aldolase are strongly conserved even between different isozymes. Furthermore, in the 3'-untranslated regions of the mRNAs for the B isozyme of human and rat there is an extensive stretch of homology. Aldolase B lacks a cysteine at positions 72 and 338 and lacks a histidine at position 361. These residues, which are present in rabbit aldolase A, have previously been proposed to take part in catalysis. Our findings suggest that this may not be the case.
A new human species of aldolase A mRNA from fibroblasts
European Journal …, 1987
A full-length cDNA aldolase A clone was isolated from a human fibroblast cDNA library and completely sequenced. Excluding the poly(A) tail, the clone covers 1095 base pairs (bp) bf the coding region, plus 199 bp downstream for the termination codon and 146 bp upstream for the initiation codon, within a total of 1440 bp. Primer extension experiments performed with human cultured fibroblast mRNA indicate an elongated product of a further 40 bp. These results evaluated together with those obtained in a concurrent study concerning aldolase A mRNA isolated from human liver are direct evidence of aldolase A mRNA multiplicity in man. The data also suggest the existence in mammals of three different classes of aldolase A mRNA, which would account for tissue specificity and resurgence of foetal expression in tumors.
Localization of aldolase C mRNA in brain cells
FEBS Letters, 1990
The expression of aldolase C and aldolase A mRNA was assessed by Northern blot hybridization using RNAs purified from cultured rat and mouse brain neurons and astroglial cells. Neurons were found to contain about 4-fold more aldolase C mRNA and about twice as much aldolase A mRNA than astroglia. Analysis of the cellular localization of aldolase C mRNA by in situ hybridization to brain slices showed a predominantly neuronal labeling with an irregular distribution. A strong signal was observed in Purkinje cell somata and a weaker signal in subpopulations of neurons in cerebral cortex, striatum, hippocampus, hypothalamic nuclei and primary olfactory cortex. Aldolase C; Brain cell; Hybridization in situ Published by Elsevier Science Publishers B. V. (Biomedical Division) 00145793/90/$3.50
Human aldolase C: gene transcriptional regulation and protein functional role
2011
Aldolase C is the brain-specific aldolase isoenzyme. In the human brain, aldolase C messenger and protein are expressed in a stripe-like pattern in the Purkinje cells of the cerebellum, in the inferior olives and in the Goll and Burdach nuclei of the posterior horn in the spinal cord. Notwithstanding numerous studies have been conducted on aldolase C transcriptional regulation, promoter regions governing brain- and cell-specific expression in human are not yet precisely known. We analysed transcriptional regulation of human aldolase C gene through in vitro and in vivo systems. We previously demonstrated that cAMP increased human aldolase C gene expression in PC12 cells through NGFI-B binding to element D in the distal promoter region of the gene. Here we demonstrate that NGF up-regulates human aldolase C gene expression in PC12 cells. We identified the element E in the distal promoter region as responsive to NGF treatment and demonstrated that USF1 binds to this region thus mediatin...
Comparative Biochemistry and Physiology Part A: Physiology, 1997
A 2061 bp cDNA encoding a goldfish (Carassius auratus) aldolase was isolated from a goldfish brain library. The deduced 362 amino acid sequence is more similar to vertebrate brain (aldolase C) and muscle aldolases (aldolase A) than to the liver isozymes (aldolase B). Northern blot analysis indicates strong expression of the mRNA in brain but not in liver or muscle, which indicates that this is aldolase C rather than aldolase A. Analysis of all known vertebrate aldolase amino acid sequences reveals five residues; Leu-57, Arg-314, Thr-324, Glu-332, and Gly-350 that are present exclusively in aldolase Cs. The goldfish clone possesses all five residues. The residues are primarily located in the carboxyl-terminal region of the enzyme and may play a role in determining the neuronal isozyme-specific properties of the enzyme. Furthermore, the existence of an aldolase C in a teleost fish has implications with respect to the timing of genome duplication events that are thought to have been critical in vertebrate evolution. comp biochem physiol 117A;4:471-476, 1997. © 1997 Elsevier Science Inc.
European Journal of Biochemistry, 1993
A 115-bp promoter fragment of the aldolase C gene is sufficient for conferring neural cell specificity on a reporter gene, in cultured PC12 cells and in transgenic mice. In vitro DNase I protection experiments detected two footprints on the promoter, termed boxes A/A', and B. The 5' NA' box contains overlapping Spl and Krox2O/Krox24 binding sites; it binds Spl in fibroblasts (box A') and a different complex in brain (box A). Any deletion or mutation of this box that impairs protein recognition also suppresses promoter activity. The replacement of box MA' by a Spl consensus binding site results in the loss of the brain specificity of expression in transgenic mice. Further 3', box B is composed of a 5' direct repeat and a 3' GC box consisting of overlapping Spl and Krox20/Krox24 binding sites. Mutation of the direct repeat subregion appears to be more deleterious for the promoter activity than mutation of the G+C-rich subregion.