A novel deletion mutation of lactate dehydrogenase A(M) gene in fifth family with the enzyme deficiency.
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Adolescent↗
Biomedical subjects
S S Li
Publications and source records attributed to S S Li.
Expression of human prostatic acid phosphatase and prostate specific antigen genes in neoplastic and benign tissues.
Expression of human prostatic acid phosphatase (ACPP) and prostate specific antigen (PSA) genes in prostatic carcinoma (CAP) and benign prostatic hyperplasia (BPH) was investigated by northern blot analyses. The expressions of ACPP and PSA, as well as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase-muscle (LDH-A), were elevated significantly in prostatic carcinoma when compared with the expressions of these genes in benign prostatic hyperplasia in the same patient. The expression of the actin gene in both neoplastic and benign hyperplasia remained the same.
Acid Phosphatase↗
Fast-type electrophoretic variant of lactate dehydrogenase M(A) and comparison with other missense mutations in lactate dehydrogenase M(A) and H(B) genes.
An electrophoretic variant of lactate dehydrogenase (LD) M(A) subunit was discovered in a female patient with chest pain. Her LD activity in serum was within the normal reference interval, and analysis of her LD isoenzyme pattern showed an abnormal migration indicating a fast-type LD-M(A) subunit variant. DNA analysis of the mutant LD-M gene detected a single base substitution, an A to G transition at codon 220 (AAA-->GAA). This mutation resulted in the replacement of a lysine by a glutamic acid (mutation K220E) and produced a subunit variant (electrophoretic fast type). This missense mutation was also observed in the patient's son, and genotypes of mother and son were consistent with their biochemical phenotypes, as evaluated by LD isoenzyme analysis.
Base Sequence↗
Nucleotide sequence of human prostatic acid phosphatase ACPP gene, including seven Alu repeats.
The protein-coding sequence of the human ACPP gene was shown to be interrupted by nine introns. The length of intron 1 was at least 5kb, while the sizes of introns 2 to 9 were estimated to be 3.4Kb, 0.5Kb, 5.5Kb, 5.0Kb, 2.0Kb, 5.0Kb, 2.5Kb and 3.5Kb, respectively. Therefore, the human ACPP gene has the size of more than 40kb. Thus far, the genomic sequence of 16,273 nucleotides, including the putative promoter region and seven Alu-repeats, have been determined. Three of these Alu-repeats are located immediately upstream to exon 1 and another is identified in intron 1. All of these Alu-sequences exhibit more than 85% identity to the consensus Alu-sequence.
Acid Phosphatase↗
Molecular cloning and expression of cDNAs encoding two isoforms of protein phosphatase 2C beta from mouse testis.
Two isoforms of protein serine/threonine phosphatase were isolated and sequenced from mouse testis. A deletion of 48 nucleotides of PP2C beta 4 cDNA in comparison with PP2C beta 3 cDNA resulted in different COOH-terminal sequences of 12 and 15 amino acids, respectively. These COOH-terminal sequences of PP2C beta 3 and PP2C beta 4 were further found to be different from those of isoforms MPP beta 1 and MPP beta 2 of mouse PP2C beta reported (Terasawa, et al. Arch. Biochem. Biophys. 307: 342-349, 1993). The common sequence of 378 amino acids from these four isoforms of mouse PP2C beta exhibited 95% identity with the corresponding sequence of rat PP2C beta. The mRNAs of approximately 2.0 Kb for PP2C beta 3 and PP2C beta 4 were expressed only in testis, while the mRNAs of 3.3 Kb and 8.5 Kb for MPP beta 1 and MPP beta 2, respectively, were found in somatic tissues.
Amino Acid Sequence↗
Premature termination mutations in two patients with deficiency of lactate dehydrogenase H(B) subunit.
Two patients with low lactate dehydrogenase (LD) activity were discovered during healthcare examinations and were found to be homozygous for LD-H (heart) subunit deficiency by electrophoretic isoenzyme analysis of serum and erythrocyte hemolysate. The molecular nature of the genetic mutations was characterized by amplification by the polymerase chain reaction and DNA sequencing. In one case, a single-base substitution (T-->G transversion) at codon 147 of the LD-H(B) gene resulted in a nonsense mutation; in the other case, a deletion of 2 base pairs had occurred at codon 139, resulting in a frameshift translation and premature termination.
Adult↗
Sequence analysis of mouse cDNAs encoding ribosomal proteins L12 and L18.
Mouse cDNAs encoding ribosomal proteins (r-proteins), L12 and L18, were isolated and their sequences determined. The L12 cDNA was found to contain 639 bp, including a coding sequence of 498 nucleotides (nt), 5' (78 nt) and 3' (45 nt) untranslated regions (UTRs), and a poly(A) tail of 18 nt. The L18 cDNA was shown to consist of 648 bp, including a coding sequence of 567 nt, 5' (26 nt) and 3' (39 nt) UTRs, and a poly(A) tail of 16 nt. The nt sequences of the protein-coding region from the mouse L12 and L18 cDNAs were found to exhibit 96% and 92% identity, respectively, with those of the rat. With the use of mouse L12 and L18 cDNA probes, multiple (at least 10) copies of the L12 and L18 gene families were shown to be present in the mouse and rat genomes. However, there was no sequence heterogeneity detected among seven L18 cDNA clones, indicating that only one copy of the L18 gene-related sequences is functional, and the other copies are presumably nonfunctional pseudogenes. The complete amino acid (aa) sequences of the mouse r-proteins, L12 and L18, were deduced from the nt sequences of their cDNA clones. L12 has 165 aa and a M(r) of 17,790, while L18 has 188 aa and a M(r) of 21,570. The aa sequences of the mouse r-proteins, L12 and L18, exhibit 98% and 94% identity, respectively, to those of rat.
Amino Acid Sequence↗
Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein.
Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines.
Amino Acid Sequence↗
The prostatic acid phosphatase (ACPP) gene is localized to human chromosome 3q21-q23.
Human prostatic acid phosphatase (ACPP) has been used as a diagnostic marker for prostate cancer. It is synthesized under androgen regulation and secreted by the epithelial cells of the prostate gland. We have confirmed the previous assignment of the ACPP gene to chromosome 3 by probing a panel of 25 human-Chinese hamster somatic cell hybrids, and we have further localized the ACPP gene to chromosome 3q21-q23 by fluorescence in situ hybridization.
Acid Phosphatase↗
Analysis of a genetic mutation in an electrophoretic variant of the human lactate dehydrogenase-B(H) subunit.
An electrophoretic variant of the lactate dehydrogenase (LDH)-B(H) subunit was discovered in a patient with diabetes mellitus. His LDH activity in serum was slightly lower than normal and the LDH isozyme pattern showed an abnormal migration indicating an LDH-B subunit variant of the fast type. The LDH containing the variant subunit revealed a decreased heat stability. DNA analysis of the variant allele detected a base substitution, an A to G transition, at codon 6 (AAA-->GAA). The mutation resulted in the replacement of a lysine by a glutamic acid (K6E). The change may cause the heat instability and affect the net charge of the variant subunit, resulting in an electrophoretic LDH-B subunit variant of the fast type.
Aged↗
Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydrogenase-B(H) deficiency using DNA conformation polymorphism analysis and silver staining.
Human lactate dehydrogenase (LDH)--B(H) mutant genes were analyzed by polymerase chain reaction (PCR) and DNA conformation polymorphism. We used polyacrylamide gradient gel and silver staining procedures for DCP analysis, and observed abnormal migration patterns in individuals heterozygous for the LDH-B deficiency. Subsequent sequence determination of the mutant alleles consistently resulted in detection of three single base substitutions (transversions), viz., a C to A at residue "35" (GCG, Ala-->GAG, Glu), a T to G at residue "172" (TTT, Phe-->GTT, Val), and an A to T at residue "176" (ATG, Met-->TTG, Leu). Furthermore, mismatched PCR or amplification refractory mutation system was developed for the rapid screening and confirmation of these mutations. These amino acid replacements may cause conformational changes in neighboring residues; this probably affects the active site arrangement and results in the loss of enzyme activity.
Amino Acid Sequence↗
Characterization of capacitation inhibitory protein from rabbit seminal plasma: homology with human annexins.
A protein was purified from rabbit seminal plasma using preparative acrylamide disc electrophoresis, ammonium sulfate precipitation and gel filtration. The protein inhibited the in vitro fertilization of mouse ova inseminated with epididymal sperm and with capacitated sperm. The inhibition was not observed, however, when only ova were exposed to the protein prior to mixing with sperm. The partial protein sequence analysis revealed the strong homology of the rabbit fertilization inhibitory protein to human annexin V.
Amino Acid Sequence↗
Molecular cloning, nucleotide sequence and expression of a cDNA encoding an intracellular protein tyrosine phosphatase, PTPase-2, from mouse testis and T-cells.
The PTP-2 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase-2) was isolated and sequenced from mouse testis and T-cell cDNA libraries. This PTP-2 cDNA was found to be homologous to human PTP-TC and rat PTP-S, and contained 1,551 nucleotides, including 1,146 nucleotides encoding 382 amino acids as well as 5' (61 nucleotides) and 3' (344 nucleotides) non-coding regions. Northern blot analysis indicated that PTP-2 mRNA of 1.9 Kb was most abundant in testis and kidney, although it was also present in spleen, muscle, liver, heart and brain.
Amino Acid Sequence↗
The cDNA cloning, nucleotide sequence and expression of an intracellular protein tyrosine phosphatase from mouse testis.
The PTP-1 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase) was isolated and sequenced from a mouse testis cDNA library. This PTP-1 cDNA was found to contain an open reading frame of 1,296 nucleotides as well as 5' (83 nucleotides) and 3' (289 nucleotides) non-coding regions. The deduced sequence of 432 amino acids of mouse PTPase-1 exhibited 93% and 83% identity to that of rat PTPase-1 and human PTPase-1B, respectively. Thus, this PTP-1 is a mouse homologue of human PTP-1B and rat PTP-1. Northern blot analysis indicated that PTP-1 mRNAs were most abundant in testis, and were detected in sizes of 4.4 Kb, 2.4 Kb and 2.2 Kb, 2.0 Kb. The PTP-1 transcripts of 4.4 Kb and 2.0 Kb, but not 2.4 Kb and 2.2 Kb, were also present in kidney, spleen, muscle, liver, heart and brain. Genomic blot analysis showed that a single copy of the PTP-1 gene is contained in the mouse genome and that introns are present in mammalian PTP-1 genes.
Amino Acid Sequence↗
Structure of human prostatic acid phosphatase gene.
Two cDNA clones containing the complete protein-coding sequence of 1,188 nucleotides as well as the 5' and 3' non-coding regions of human prostatic acid phosphatase (PAP) were isolated and sequenced. The size of PAP mRNAs from benign prostate hyperplasia and cancerous prostate was estimated to be 3.2Kb, indicating that the 3' downstream polyadenylation signal was used. Several genomic clones containing parts of the human PAP gene were isolated and the nucleotide sequence of ten exons and their flanking regions was determined. The protein-coding sequence of the human PAP gene was interrupted by nine introns. The positions of all nine introns present in the human PAP gene were homologous to those of the first nine introns in the human lysosomal acid phosphatase (LAP) gene. However, the last (11th) exon of the LAP gene encoding the COOH-terminal domain, which includes a transmembrane segment, was found to be absent in human PAP gene. Southern blot analysis of ten mammalian genomic DNAs gave multiple EcoRI fragments. The data of human genomic DNAs were consistent with the total length of the PAP gene of at least 50 kilobases.
Acid Phosphatase↗
Human centrosomal epitope is shared specifically with human lactate dehydrogenase-B isozyme.
A rabbit serum (0013) used to identify pericentriolar proteins from isolated centrosomes (Gosti-Testu, F., Marty, M.C., Berges, J., Maunoury, R. and Bornens, M. (1986) EMBO J. 5, 2545-2550) was shown also to react through the same epitope with several non-centrosomal proteins including a major 36 kDa cytosolic antigen. This protein was identified to be human lactate dehydrogenase and the co-distribution of 0013 epitope on the centrosomal protein and on lactate dehydrogenase (LDH) was shown to be specific for human cells (Gosti, F., Marty, M.C., Courvalin, J.C., Maunoury, R. and Bornens, M. (1987) Proc. Natl. Acad. Sci. USA 84, 1000-1004). Human hepatic cells constitute, so far, the only exception to this co-distribution rule. By using this cell type which expresses only the LDH-A4 isozyme, we demonstrate that 0013 epitope is specific for the human LDH-B subunit, making serum 0013 the strongest anti-LDH-B available so far. The evolutionary and physiological significance of this situation is discussed.
Biological Evolution↗
Molecular characterization of genetic mutations in human lactate dehydrogenase (LDH) B (H) variant.
We have previously detected a single base substitution of G by A at the Arg codon CGC in exon 4 of the mutant lactate dehydrogenase (LDH) gene, an unstable LDH-B variant (case 1). Here, we use the polymerase chain reaction (PCR) to amplify genomic DNA of two cases (the original case 1 and a new patient, case 2). We were able to confirm that case 1 is homozygous for the mutation, causing a replacement of the conserved Arg by His at residue 173. The resulting LDH-B variant subunit is unstable in vivo. Whereas the mutation in exon 4 was not observed in case 2, a different single base substitution of A by C was detected at the Ser codon AGT in exon 3. This mutation causes a replacement of the conserved Ser by Arg at residue 131. Genomic analysis of the family of case 2 by mismatched PCR showed that the missense mutation was consistent with their biochemical phenotypes. The replacement results in a conformational change of the residues near the Ser, probably because the side chain of Arg is much more bulky than that of Ser. The change may affect the arrangement of the cofactor binding site and result in the loss of enzyme activity. The experimental observations are consistent with computer graphics analyses.
Amino Acid Sequence↗
Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit.
An electrophoretic variant of lactate dehydrogenase-A (M) subunit was discovered in a patient with multiple myeloma. DNA analysis of the variant allele revealed a nucleotide substitution (transition) of C to T at codon 314 (CGT-TGT), and this mutation resulted in the replacement of an arginine by a cysteine (R314C). This amino acid replacement affects the net charge of the subunit and makes the LDH-A variant have a faster electrophoretic mobility. The responsible missense mutation created a new restriction site, AGGCCT, which can be simply detected by endonuclease AatI digestion. In addition, four synonymous substitutions with no amino-acid replacements were found at codons 51, 119, 163 and 175 in the LDH-A gene from the patient.
Aged↗