Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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In Ustilago maydis, pathogenic development is controlled by the multiallelic b-mating type locus. b encodes two different homeodomain proteins, bE and bW, that dimerize only when they originate from different alleles. The heterodimer is thought to act as a transcriptional regulator of pathogenicity genes. To address the contribution of individual homeodomains to the function of the hetereodimer, amino acids presumed to be critical for the function of homeodomains were altered by introducing deletions and single amino acid substitutions. This analysis demonstrated that both homeodomains are essential for function of the bE/bW complex. All point mutations affecting conserved amino acids in bW resulted in non-functional proteins. For bE the mutational analysis revealed that certain features of the homeodomain, like base-specific contacts and contacts to the sugar phosphate backbone, contribute to function. However, the structural requirements for function of the bE homeodomain appear to be more flexible than those of the bW homeodomain. We compare our data with the related systems in Schizophyllum commune, Coprinus cinereus and Saccharomyces cerevisiae.
Mol Gen Genet 1997 May 20
PMID:The homeodomains of the heterodimeric bE and bW proteins of Ustilago maydis are both critical for function. 919 10

We have isolated and characterized Tgmr, a copia-like retrotransposon, linked tightly to the Rps1-k allele that confers race-specific resistance of soybean to the the fungal pathogen Phytophthora sojae. Southern analysis followed by PCR and sequence analyses, using primers based on sequences flanking the insertion site confirmed that the element was inserted in the neighboring region of Rps1-k but not in that of the other four Rps1 alleles. This implies that Tgmr was transposed into the Rps1-k flanking site after the divergence of Rps1 alleles. Southern analysis of a series of diverse soybean cultivars revealed a high level of polymorphism of Tgmr-related sequences. These results indicate that this low copy retroelement family could have been active in the soybean genome in the recent past. Tgmr contains long terminal repeats (LTR) and four non-overlapping open reading frames (ORF), presumably originating from mutations leading to stop codons of a single ORF. The conserved domains for gag, protease, integrase, reverse transcriptase and RNaseH are present in the internal portion of the element. However, the protease, reverse transcriptase and RNaseH of this element are non-functional due to the presence of several stop codons. Possible transactivation of Tgmr and application of this element in insertional mutagenesis for soybean are discussed.
Plant Mol Biol 1997 May
PMID:A copia-like retrotransposon Tgmr closely linked to the Rps1-k allele that confers race-specific resistance of soybean to Phytophthora sojae. 920 41

The parA system of plasmid R1 consists of two genes, parM and parR, and a cis-acting centromere-like site parC. The ParM protein exhibits similarity with a superfamily of ATPases that includes actin, hsp70 and hexokinase. ParM was purified to near-homogeneity and assayed for in vitro ATPase activity. The wild-type ParM protein was found to posses ATPase activity. Mutant ParM derivatives that exhibited decreased in vitro ATPase activity were non-functional in vivo, indicating that the ATP turnover by ParM is essential for correct plasmid partitioning. The mutant ParM proteins exhibited trans-dominance, suggesting that ParM participates as a structural component of the partitioning apparatus. The ATPase activity of ParM was activated slightly by the presence of ParR and activated to a much greater extent when ParR was bound to the centromere-like parC region. An analysis using the yeast two-hybrid system indicated that ParM and ParR interact, and demonstrated that ParR interacts with itself. Thus our results suggest a direct interaction of ParM and ParR at the natural partition site parC, and that the ATPase activity of ParM is specifically stimulated by this interaction.
J Mol Biol 1997 Jun 20
PMID:Partitioning of plasmid R1. The ParM protein exhibits ATPase activity and interacts with the centromere-like ParR-parC complex. 921 56

Type I collagen is the most prevalent member of the fibril forming family of collagens in higher vertebrates and its heterotrimeric form is comprised of two alpha 1(I) chains and one alpha2(I) polypeptide chain. The functional importance of having two distinct chain types in type I collagen is largely undefined. The existence of a mouse model with a Cola-2 gene mutation (termed oim) that results in non-functional pro alpha 2(I) chains presents a unique opportunity to explore changes in collagen structure resulting from the complete (oim/oim mice) and partial (oim/+ mice) loss of functional alpha 2(I) chains. Tail tendon is a tissue with a well-defined, hierarchical organization of type I collagen. X-ray diffraction studies on oim/oim versus control tendons indicate that the total absence of alpha 2(I) chains results in a decrease in the order of axial packing and a loss of crystalline lateral packing. This suggests that the non-equivalence of three chains is an important determinant of lateral interactions between adjacent molecules and may be involved in the long-range axial order in type I collagen-containing tissues. Both homotrimeric and heterotrimeric type I collagen molecules are found in heterozygous oim mice and these appear to be present in the same co-polymeric fibrils, preventing crystalline lateral packing. In addition to these changes at a fibrillar level, the absence of the alpha 2(I) chain results in an increased enzymatic susceptibility at one site. The oim/oim mice are observed to have reduced body size and smaller tendon bundles, which may be a consequence of these molecular and fibrillar changes in collagen. Furthermore, it is likely that a similar alteration in the molecular packing of collagen in bone fibrils contributes to the osteopenia and decreased bone strength in mice with the oim mutation that are also characteristic of human osteogenesis imperfecta.
J Mol Biol 1997 Jul 11
PMID:Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain. 923 28

Pyrroloquinoline quinone (PQQ), a novel cofactor of biological redox processes, is ubiquitous in animal cells. We have examined the effects of PQQ on protein synthesis. PQQ inhibits protein synthesis in hemin-supplemented rabbit reticulocyte lysates. This inhibition is characterized by increased phosphorylation of eIF-2alpha and by diminished guanine nucleotide exchange activity of eIF-2B. The increased eIF-2alpha phosphorylation is the result of activation by PQQ of the heme-regulated eIF-2alpha kinase (HRI). The addition of 10 microM PQQ completely inhibits the increase in protein synthesis that occurs on the addition of hemin (20 microM) to heme-deficient lysates, whereas a lower concentration of PQQ (100 nM) causes a very slight stimulation of protein synthesis. The increased eIF-2alpha phosphorylation that occurs at high concentrations of PQQ inhibits eIF-2B activity, presumably due to formation of a 15S complex [eIF-2(alphaP).eIF-2B] in which eIF-2B becomes non-functional. Low concentrations of PQQ (0.1-1 microM) do not affect eIF-2alpha phosphorylation, but rather enhance the guanine nucleotide exchange activity of eIF-2B in reticulocyte lysates. In Chinese hamster ovary cell extract which is devoid of significant eIF-2alpha kinase activity, addition of both low and high concentrations of PQQ results in an increase in eIF-2B activity. The addition of PQQ to reticulocyte lysates activates HRI whereas addition of PQQ to purified HRI in vitro inhibits the autokinase and eIF-2alpha kinase activity of the HRI; the inhibition of purified HRI by PQQ is observed both in the presence and absence of hemin. These findings suggest that PQQ inhibits purified HRI by acting as an oxidant whereas in lysates in which PQQ is readily reduced, the PQQ acts as a reductant and increases the activities of both HRI and eIF-2B.
Blood Cells Mol Dis 1997 Aug
PMID:The effects of pyrroloquinoline quinone on heme-regulated eIF-2alpha kinase and eIF-2B activities in eukaryotic protein synthesis. 923 56

Mutations of the androgen receptor (AR) gene and protein are associated with complete androgen insensitivity syndromes (CAIS) in individuals with XY genotypes causing them to develop as phenotypic females. Splice site mutations of the AR gene are very rare and in this report we describe the consequences of a novel G --> A mutation at the exon 7/intron 7 splice junction of the AR gene that resulted in CAIS in two siblings. Reverse transcriptase-polymerase chain reaction (RT-PCR) of the AR transcript in patient's fibroblasts was performed and sequencing of the product showed omission of exon 7, with exon 6 being spliced directly to exon 8. This resulted in a shift of the reading frame and the introduction of a premature stop codon 10 amino acids into exon 8. Immunoblot analyses showed that the resultant AR protein was partially deleted in its C-terminal region and was approximately 1.5 kDa smaller than the wild type. This truncated AR was non-functional as it was unable to bind its physiological ligand (dihydrotestosterone) in androgen-binding assays. This is the first documentation of a point mutation in the AR gene which causes exon skipping and proves that the mutation is the cause of CAIS in our two subjects.
Mol Cell Endocrinol 1997 Aug 08
PMID:A novel splice site mutation in the androgen receptor gene results in exon skipping and a non-functional truncated protein. 929 79

The diploid Lotus japonicus was previously suggested as a model for the legume plant family. We present here the nucleotide sequence and the derived gene organization of a small part of the genome in this model plant. Two functional genes with the same transcriptional orientation were identified within the 23326-bp genomic region analysed. The LjGln1 gene encodes a cytosolic glutamine synthetase and the LjKrm (Kinesin repeat motif) gene encodes a polypeptide with similarity to a repeated motif present in the microtubule-associated kinesin light chain protein. Transcripts of the glutamine synthetase gene are found primarily in roots and root nodules, while transcripts of the Krm gene are found in roots, root nodules and leaves. In the region between Gln1 and Krm, the presence of a third gene, Pge1, was suggested by analysis with the Grail exon recognition program. Upstream of the Gln1 gene a segment carrying two apparently non-functional, fragmented copia-like retroelements, dRtp1 and dRtp2, was identified. Sequence similarity to reverse transcriptase- and RNaseH-coding regions defined the defective retro-elements dRtp1 and dRtp2 within this segment. Terminal repeats were not found but three different sets of short direct repeats are located adjacent to the dRtp1 element. The three genes and the incomplete retroelements occupy most of the analysed DNA, leaving approximately one-fifth of the chromosome fragment without recognisable genome constituents.
Mol Gen Genet 1997 Aug
PMID:Organization and expression of genes in the genomic region surrounding the glutamine synthetase gene Gln1 from Lotus japonicus. 932 67

Recombination is believed to prevent genetic deterioration in sexual populations because it allows conservation of functional genotypes by removing deleterious mutations. Moreover, evidence that non-recombining segments of a genome deteriorate is provided by genetic experiments in Drosophila and yeast. Y chromosomes generally do not recombine along most of their length, and thus Y chromosome genes, despite having been selectively maintained for their function, could be lost from the genome. Here we present definitive evidence that functional Y genes can be lost from the mammalian genome. TSPY genes must have been selectively maintained on the mammalian Y chromosome since before the radiation of eutheria, 80 million years ago, as they are found conserved on the Y chromosome in two mammalian orders: primate and artiodactyl. We have now identified TSPY on the rodent Y chromosome, in mouse and rat. The gene structure and expression of rat TSPY suggest that it is a functional, testis-specific gene, but the closely related mouse gene, Tspy, has clearly become non-functional, producing only low levels of aberrantly spliced transcripts. Thus TSPY lost its function in the mouse lineage after its divergence from the rat lineage. So, in the case of Tspy at least, the absence of recombination does appear to have led to the loss of a functional gene.
Hum Mol Genet 1998 Mar
PMID:Rodent Y chromosome TSPY gene is functional in rat and non-functional in mouse. 946 17

Multicentric chromosomes are often found in tumor cells and certain cell lines. How they are generated is not fully understood, though their stability suggests that they are non-functional during chromosome segregation. Growing evidence has implicated microtubule motor proteins in attachment of chromosomes to the mitotic spindle and in chromosome movement. To better understand the molecular basis for the inactivity of centromeres associated with secondary constrictions, we have tested these structures by immunofluorescence microscopy for the presence of motor complexes and associated proteins. We find strong immunoreactivity at the active, but not inactive, centromeres of prometaphase multicentric chromosomes using antibodies to the cytoplasmic dynein intermediate chains, three components of the dynactin complex (dynamitin, Arp1 and p150 Glued ), the kinesin-related proteins CENP-E and MCAK and the proposed structural and checkpoint proteins HZW10, CENP-F and Mad2p. These results offer new insight into the assembly and composition of both primary and secondary constrictions and provide a molecular basis for the apparent inactivity of the latter during chromosome segregation.
Hum Mol Genet 1998 Apr
PMID:Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres. 949 20

We report the molecular cloning of Drosophila genes encoding putative lipase homologs, Dm lip1, lip2 and lip3, the definition of their structure and the expression patterns during development. These Drosophila lipases are related to acid lipases, with a common GHSQG motif, within a more general consensus GXSXG, identified as the active site shared by all the members of lipase superfamily. The lip1 and lip3 genes are transcribed in different tissues and developmental stages, suggesting that they have different functions. The lip1 gene, coding for a protein similar to digestive lipases, is expressed in ovaries and early embryos and, with a different sized transcript, in all the other developmental stages. The lip3 gene, whose translation product is more similar to lysosomal acid lipases, is expressed only during the larval period. The lip2 gene seems non-functional. The Drosophila putative lipases do not show similarity with the Drosophila yolk proteins that are reported to have sequence similarity with lipoprotein lipases, but share a consistent similarity with lepidopteran proteins reported as egg specific or yolk proteins, probably corresponding to lipase homologs. The results reported here are discussed in relation to the evolution and functions of lipases within the between species.
J Mol Biol 1998 Mar 13
PMID:The Drosophila melanogaster lipase homologs: a gene family with tissue and developmental specific expression. 956 93


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