Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Saccharomyces cerevisiae RAD54 gene is transcriptionally regulated by a broad spectrum of DNA-damaging agents. Induction of RAD54 by DNA-damaging agents is under positive control. Sequences responsible for DNA damage induction (the DRS element) lie within a 29-base-pair region from -99 to -70 from the most proximal transcription start site. This inducible promoter element is functionally separable from a poly(dA-dT) region immediately downstream which is required for constitutive expression. Deletions which eliminate induction of RAD54 transcription by DNA damage but do not affect constitutive expression have no effect on growth or survival of noninducible strains relative to wild-type strains in the presence of DNA-damaging agents. The DRS element is also not required for homothallic mating type switching, transcriptional induction of RAD54 during meiosis, meiotic recombination, or spontaneous or X-ray-induced mitotic recombination. We find no phenotype for a lack of induction of RAD54 message via the damage-inducible DRS, which raises significant questions about the physiology of DNA damage induction in S. cerevisiae.
Mol Cell Biol 1989 Aug
PMID:Failure to induce a DNA repair gene, RAD54, in Saccharomyces cerevisiae does not affect DNA repair or recombination phenotypes. 255 91

The analysis of a de novo 8q12.2-q21.2 deletion led to the identification of a proposed previously undescribed contiguous gene syndrome consisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydrocephalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hydrocephalus. In contrast, we report a new localization for the gene responsible for BOR syndrome which is more telomeric to an initial placement. Linkage analysis of affected families consistently mapped the gene responsible for BOR and Branchio-Oto (BO) syndromes to within the deletion. Using new algorithms, a YAC contig was constructed and used to localize the breakpoint of another chromosomal rearrangement associated with BO syndrome to a 500 kb interval within the deletion. The 8q12.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.
Hum Mol Genet 1994 Oct
PMID:A proposed new contiguous gene syndrome on 8q consists of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, a dominant form of hydrocephalus and trapeze aplasia; implications for the mapping of the BOR gene. 784 13

Mammalian aspartyl-tRNA synthetase (DRS) occurs in a multi-enzyme complex of aminoacyl-tRNA synthetases, while DRS exists as free soluble enzymes in bacteria and yeast. The properties of human DRS transient expressed in COS cells were examined. After transfection of COS cells with the recombinant plasmids pSVL-63 that contained hDRS cDNA coding and non-coding sequences, and pSV-hDRS where the non-coding sequences were deleted, DRS in the transfected COS cells significantly increased compared to mock transfected cells. COS cells transfected with pSV-hDRS delta 32 that contained N-terminal 32 residue-coding sequence deleted hDRS cDNA showed no increase in DRS activity. Northern blot analysis showed that concentrations of corresponding mRNAs of hDRS and hDRS delta 32 were greatly enhanced in transfected cells. The increases in the level of the transcripts were much higher than those of the corresponding proteins. Gel filtration analysis showed that hDRS in pSV-hDRS transfected cells expressed as a low molecular weight form of hDRS and pSV-hDRS delta 32 transfected cells did not. Epitope tagging and indirect immunofluorescence microscopy was used to localize hDRS. Both hDRSmyc and hDRS delta 32myc were localized in the cytoplasm and showed diffused patterns. These results showed that hDRS has little tendency to aggregate in vivo and suggested that the N-terminal extension in hDRS was not involved in the expression and sub-cellular localization of hDRS, but may play a role in the maintenance of enzymatic activity of hDRS in COS cells.
Mol Cell Biochem 1994 Nov 09
PMID:Expression of human aspartyl-tRNA synthetase in COS cells. 787 98

Transcription of Ty1 and Ty2 retrotransposons of the yeast Saccharomyces cerevisiae is modulated by multiple downstream regulatory sites. Both transposon families include a positively acting site within the transcribed region which resembles a higher eukaryotic enhancer. We have demonstrated the existence of a repression site distal to the enhancer of the Ty2-917 element. Here we describe experiments investigating the internal structure of this site. We show that this 200-bp region includes three distinct repression sites which we term DRSI (downstream repression site I), DRSII, and DRSIII. Individually each site causes almost twofold repression, and together the sites repress eightfold. Unexpectedly, when the entire region encompassing the DRS sites is moved outside the transcription unit, it acts as a qualitatively positively acting element. In this context the DRS sites still repress transcription, since eliminating them increases transcription further. That the region can activate transcription implies that it includes activation sites in addition to the three repression sites. The change from qualitatively negatively acting to positively acting must reflect a change in the relative effects of the multiple positive and negative sites; when moved outside the transcription unit, the activators predominate. Importantly, DRSII and DRSIII repress transcription autonomously when inserted upstream of a heterologous promoter activated by the transcriptional activator GCN4, showing that they are indeed transcriptional repression sites.
Mol Cell Biol 1993 Apr
PMID:Three downstream sites repress transcription of a Ty2 retrotransposon in Saccharomyces cerevisiae. 838 3

The GnRH receptor is an unusual member of the G protein-coupled receptor (GPCR) superfamily with several unique features. One of these is a variant of the conserved DRY motif that is located at the junction of the third transmembrane domain and the second intracellular (2i) loop of most GPCRs. In the GnRH receptor, the Tyr residue of the conserved triplet is replaced by Ser, giving a DRS sequence. The aspartate and arginine residues of the triplet are highly conserved in almost all GPCRs. The functional importance of these residues was evaluated in wild type and mutant GnRH receptors expressed in COS-7 cells. Mutants in which Asp138 was replaced by Asn or Glu were poorly expressed, but showed significantly increased internalization and exhibited augmented inositol phosphate generation to maximal agonist stimulation compared with the wild type receptor. In contrast, receptors in which Arg139 was substituted with Gln, Ala, or Ser showed reduced internalization, and the GnRH-induced inositol phosphate response for the Arg139Gln mutant was significantly impaired in proportion to its low expression level. Replacing Ser140 with Ala affected neither internalization nor signal transduction. The role of the polar amino acids at the C terminus of the 2i loop was evaluated in two additional mutants (Ser151Ala, Ser153Ala, and Ser151Ala, Ser153Ala, Lys154Gln, Glu156Gln). Both of these mutants exhibited agonist-induced inositol phosphate responses similar to that of the wild type receptor, but showed increased receptor internalization. This mutational analysis indicates that the conserved Asp and Arg residues in the DRY/S triplet make important contributions to the structural integrity of the receptor and influence receptor expression, agonist-induced activation, and internalization.
Mol Endocrinol 1997 Aug
PMID:Mutations of the conserved DRS motif in the second intracellular loop of the gonadotropin-releasing hormone receptor affect expression, activation, and internalization. 925 12

Diffuse reflectance spectroscopy has been used to investigate structural modification of mazzite zeolite subjected to calcination, acid leaching and acetylacetone treatments. Extra-framework aluminium species, formed upon expulsion of aluminium from the framework, are detected by DRS because they are involved in aluminium-oxygen charge transfer transitions. Impregnation of the calcined ammonium-exchanged and acid leached samples with ethanolic acetylacetone will convert the broadened 260-280 nm band of extra-framework aluminium with distorted symmetry to a distinct well-defined 285 nm band. The appearance of this band is due to the transformation of the aluminium atoms with a different coordination number to structures with highly ordered octahedral symmetry. Washing the acetylacetone treated samples with hot ethanol leads to extraction of some of the complexed aluminium. The presence of an extracted aluminium triacetylacetonate complex in the eluant is verified by the same spectrophotometer used in its conventional mode. This suggests that a dual DR and UV-VIS spectrophotometry is an appropriate approach to study such topics.
Spectrochim Acta A Mol Biomol Spectrosc 2001 Jan
PMID:Identification and estimation of extra-framework aluminium in acidic mazzite by diffuse reflectance spectroscopy. 1120 53

Okihiro syndrome refers to the association of forearm malformations with Duane syndrome of eye retraction. Based on the reported literature experience, clinical diagnosis of the syndrome can be elusive, owing to the variable presentation in families reported. Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mutation of the TBX5 locus and Townes-Brocks syndrome, known to be caused by mutations in the SALL1 gene. Arising from our observation of several malformations in Okihiro syndrome patients which are also described in Townes-Brocks syndrome, we postulated that Okihiro syndrome might result from mutation of another member of the human SALL gene family. We have characterized the human SALL4 gene on chromosome 20q13.13-q13.2. Moreover, we have identified literature reports of forelimb malformations in patients with cytogenetically identifiable abnormalities of this region. We here present evidence in 5 of 8 affected families that mutation at this locus results in the Okihiro syndrome phenotype.
Hum Mol Genet 2002 Nov 01
PMID:Okihiro syndrome is caused by SALL4 mutations. 1239 9

Human RNPS1 was originally purified and characterized as a pre-mRNA splicing activator, and its role in the postsplicing process has also been proposed recently. To search for factors that functionally interact with RNPS1, we performed a yeast two-hybrid screen with a human cDNA library. Four factors were identified: p54 (also called SRp54; a member of the SR protein family), human transformer 2 beta (hTra2 beta; an exonic splicing enhancer-binding protein), hLucA (a potential component of U1 snRNP), and pinin (also called DRS and MemA; a protein localized in nuclear speckles). The N-terminal region containing the serine-rich (S) domain, the central RNA recognition motif (RRM), and the C-terminal arginine/serine/proline-rich (RS/P) domain of RNPS1 interact with p54, pinin, and hTra2 beta, respectively. Protein-protein binding between RNPS1 and these factors was verified in vitro and in vivo. Overexpression of RNPS1 in HeLa cells induced exon skipping in a model beta-globin pre-mRNA and a human tra-2 beta pre-mRNA. Coexpression of RNPS1 with p54 cooperatively stimulated exon inclusion in an ATP synthase gamma-subunit pre-mRNA. The RS/P domain and RRM are necessary for the exon-skipping activity, whereas the S domain is important for the cooperative effect with p54. RNPS1 appears to be a versatile factor that regulates alternative splicing of a variety of pre-mRNAs.
Mol Cell Biol 2004 Feb
PMID:Human RNPS1 and its associated factors: a versatile alternative pre-mRNA splicing regulator in vivo. 1472 63

Previously, we have shown that pinin/DRS (Pnn), a 140-kDa nuclear and cell adhesion-related phosphoprotein, is involved in the regulation of cell adhesion and modulation of the activity of multiple tumor suppressor genes. In the nucleus Pnn is concentrated in the "nuclear speckles," zones of accumulation of transcriptional and mRNA splicing factors, where Pnn is involved in mRNA processing. Alternatively, other roles of Pnn in gene regulation have not yet been established. By utilizing in vitro pull-down assays, in vivo interaction studies, and immunofluorescence in combination with overexpression and RNA interference experiments, we present evidence that Pnn interacts with the known transcriptional corepressor CtBP1. As a consequence of this interaction Pnn was capable of relieving the CtBP1-mediated repression of E-cadherin promoter activity. Our results suggest that the interaction of Pnn with the corepressor CtBP1 may modulate repression of transcription by CtBP1. This interaction may reflect the existence of coupling factors involved in CtBP-mediated transcriptional regulation and mRNA processing events.
Mol Cell Biol 2004 Dec
PMID:Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. 1554 32

Carboxypeptidase A-6 (CPA6) was recently discovered in the human genome. To gain information regarding the potential function of this novel protein, the mouse homolog of CPA6 was identified using a combination of bioinformatics and reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, homologs in rat, chicken, and frog were identified using a bioinformatics approach. The distribution of CPA6 mRNA in mouse tissues was examined using RT-PCR and in situ hybridization. A strong RT-PCR signal is detectable in olfactory bulb, and much lower levels are present in other regions such as the cerebral cortex, hippocampus, hypothalamus, striatum, and medulla. In peripheral tissues, a moderate RT-PCR signal is present in epididymis, and low levels are detectable in colon and spleen. The high level of CPA6 in adult mouse brain olfactory bulb was confirmed by in situ hybridization. Lower levels of CPA6 mRNA were found to be present in the cingulate cortex, lateral septum, pontine nucleus, and inferior olivary nucleus of the hindbrain. Within the olfactory bulb, CPA6 mRNA is enriched in the mitral and granular layer. A lower level of CPA6 mRNA is present in the internal and external plexiform layers, and no signal is detectable in the olfactory nerve layer. The distribution was also examined in whole embryos at embryonic day 14.5 and CPA6 mRNA was found to be enriched in eye, ear, osteoblasts, stomach, skin, dorsal root ganglia, and throughout the CNS. The presence of CPA6 mRNA in the rectus muscle layer of the eye at embryonic day 14.5 is consistent with the observation that the CPA6 gene is disrupted in a patient with Duane syndrome, a congenital eye defect. Taken together, the distribution of CPA6 suggests a specific role in a limited number of tissues, and it is possible that this role involves an aspect of cell migration.
Brain Res Mol Brain Res 2005 Jun 13
PMID:Identification and distribution of mouse carboxypeptidase A-6. 1595 Jul 71


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