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

The Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1) and autoimmune polyglandular disease type I (APECED) have been mapped to human chromosome 21q22.3 by genetic linkage analysis and/or linkage disequilibrium studies. In order to isolate the genes for these disorders, we have constructed BAC contigs in this region and a 14 week trisomy 21 fetal brain cDNA library. A direct cDNA selection technique, modified to permit the recovery 5' and 3' ends of cDNA, was applied to gene identification using the BAC contigs. We have isolated and characterized a novel gene defined by three overlapping but distinct cDNAs of 5, 3, and 3 kb in size all named EHOC-1 (Epilepsy, HOloprosencephaly Candidate-1). This gene maps less than 45 kb centromeric of D21S25, and spans at least 56 kb of genomic DNA. Northern analysis of the 5 kb cDNA revealed that 8, 7.5 and 5.3 kb transcripts are ubiquitously expressed in adult tissues. DNA sequence analysis of the 5 kb cDNA showed a complete coding sequence of 3570 bp that has multiple putative transmembrane domains and has partial homologies to transmembrane proteins including sodium channel proteins. This gene (EHOC-1) is a good candidate for APECED, and particularly for EPM1 because of the location, size, structure and homologies.
Hum Mol Genet 1995 Apr
PMID:Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3. 763 21

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) translocation in childhood acute pro-B-cell leukemia, encodes a hybrid protein that contains the paired trans-activation domains of E2A (E12/E47) linked to the basic region/leucine zipper DNA-binding and dimerization domain of hepatic leukemia factor (HLF). To assess the transforming potential of this novel gene, we introduced it into NIH 3T3 murine fibroblasts by using an expression vector that also contained the neomycin resistance gene. Cells selected for resistance to the neomycin analog G418 formed aberrant colonies in monolayer cultures, marked by increased cell density and altered morphology. Transfected cells also grew readily in soft agar, producing colonies whose sizes correlated with E2A-HLF expression levels. Subclones expanded from colonies with high levels of the protein reproducibly formed tumors in nude mice and grew to higher plateau-phase cell densities in reduced-serum conditions than did parental NIH 3T3 cells. By contrast, NIH 3T3 cells expressing mutant E2A-HLF proteins that lacked either of the bipartite E2A trans-activation domains or the HLF leucine zipper domain failed to show oncogenic properties, including anchorage-independent cell growth. Thus, both of the E2A trans-activation motifs and the HLF leucine zipper dimerization domain are essential for the transforming potential of the chimeric E2A-HLF protein, suggesting a model in which aberrant regulation of the expression pattern of downstream target genes contributes to leukemogenesis.
Mol Cell Biol 1995 Jun
PMID:E2A-HLF-mediated cell transformation requires both the trans-activation domains of E2A and the leucine zipper dimerization domain of HLF. 776 Aug 20

We have examined the expression of protein tyrosine phosphatase genes in the embryonic brain of mouse and rat with reverse transcription-polymerase chain reaction. Several receptor and cytoplasmic types of tyrosine phosphatase genes were detected. Among them a novel gene was identified from mouse and rat brain, respectively. The partial amino acid sequences reveal that the new genes found in the developing brain of mouse and rat are homologous each other. Since they retain conserved phosphatase sequences, they may represent a family of protein tyrosine phosphatase gene that is commonly expressed in rodent brain.
Biochem Mol Biol Int 1994 Aug
PMID:Expression of protein tyrosine phosphatase genes in the developing brain of mouse and rat. 780 49

Using transgenic mice, we have defined novel gene regulatory elements, termed "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell-specific enhancer domain in the human adenosine deaminase (ADA) gene. Facilitators were essential for gene copy-proportional and integration site-independent reporter expression in transgenic thymocytes, but they had no effect on the enhancer in transfected T cells. Both segments were required. Individual segments had no activity. A lack of facilitator function caused positional susceptibility and prevented DNase I-hypersensitive site formation at the enhancer. The segments were required to be at opposed ends of the enhancer, and they could not be grouped together. Reversing the orientation of a facilitator segment caused a partial loss of function, suggesting involvement of a stereospecific chromatin structure. trans-acting factor access to enhancer elements was modeled by exposing nuclei to a restriction endonuclease. The enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type-specific fashion. However, unlike DNase I hypersensitivity and gene expression, accessibility to the endonuclease could occur without the facilitator segments, suggesting that an accessible chromatin domain is an intermediate state in the activational pathway. These results suggest that facilitators (i) are distinct from yet positionally constrained to the enhancer, (ii) participate in a chromatin structure transition that is necessary for the DNase I hypersensitivity and the transcriptional activating function of the enhancer, and (iii) act after cell-type-specific accessibility to the enhancer sequences is established by factors that do not require the facilitators to be present.
Mol Cell Biol 1995 Feb
PMID:Dissecting a locus control region: facilitation of enhancer function by extended enhancer-flanking sequences. 782 28

We have isolated a novel gene from the Prader-Willi syndrome (PWS) smallest region of deletion overlap in proximal human chromosome 15q. IPW (Imprinted gene in the Prader-Willi syndrome region) was isolated using the direct selection method and yeast artificial chromosomes localized to the deletion region. IPW is spliced and polyadenylated but its longest open reading frame codes for only 45 amino acids, suggesting that it functions as an RNA, similar to H19 and XIST. The RNA is widely expressed in adult and fetal tissues and is found in the cytoplasmic fraction of human cells, which is also the case for the H19 non-translated RNA, but differs from the XIST RNA which is found predominantly in the nucleus. Using a sequence polymorphism, exclusive expression from the paternal allele in lymphoblasts and fibroblasts was demonstrated; monoallelic expression was found in fetal tissues. IPW is located about 150 kb distal to SNRPN, the only other known gene in the deletion interval, and about 50 kb proximal to the breakpoint of a translocation which defines the distal end of the PWS region and the proximal end of the Angelman syndrome (AS) region. As is the case with SNRPN, PWS patients with 15q11-q13 deletions do not express IPW, whereas expression is normal in Angelman syndrome patients. Lack of expression of IPW may contribute to the PWS phenotype directly. Alternatively, the mRNA product of IPW may play a role in the imprinting process, acting either on genes located proximally in the PWS region or distally in the AS region.
Hum Mol Genet 1994 Oct
PMID:Identification of a novel paternally expressed gene in the Prader-Willi syndrome region. 784 16

DNA polymerases (Pol) alpha, delta and epsilon are necessary for replication of nuclear DNA. Pol delta interacts permanently or transiently with numerous accessory proteins whose identification may shed light on the function(s) of Pol delta. In vitro mutagenesis was used to induce thermosensitive (ts) mutations in the DNA polymerase delta gene (POL3). We have attempted to clone two recessive extragenic suppressors of such ts mutants (sdp1 for mutation pol3-14 and sdp5-1 for mutation pol3-11) by transforming thermoresistant haploid strains pol3-14 sdp1 and pol3-11 sdp5-1 with wild-type genomic libraries in singlecopy or multicopy vectors. None of the thermosensitive transformants so obtained was identified as being sdp1 or sdp5-1. Instead, three genes were cloned whose products interfere with the activity of suppressors. One of them is the type 1 protein phosphatase gene, DIS2. Another is a novel gene, ASM4, whose gene product is rich in asparagine and glutamine residues.
Mol Gen Genet 1995 Jan 20
PMID:Suppressors of thermosensitive mutations in the DNA polymerase delta gene of Saccharomyces cerevisiae. 786 92

In Schizosaccharomyces pombe, meiosis is initiated by conditions of nutrient deprivation. Mutations in genes encoding elements of the cyclic AMP-dependent protein kinase (cAPK) pathway interfere with meiosis. Loss-of-function alleles of genes that stimulate the activity of cAPK allow cells to bypass the normal requirement of starvation for conjugation and meiosis. Alternatively, loss-of-function alleles of genes that inhibit cAPK lead to the inability to undergo sexual differentiation. The cgs1+ gene encodes the regulatory subunit of cAPK, and the cgs2+ gene encodes a cyclic AMP phosphodiesterase. Thus, both genes encode proteins which negatively regulate the activity of cAPK. Loss of either cgs1 or cgs2 prevents haploid cells from conjugating and diploid cells from undergoing meiosis. In addition to these defects, cells are unable to enter stationary phase. We describe a novel gene, sak1+, which when present on a plasmid overcomes the aberrant phenotypes associated with unregulated cAPK activity. Genetic analysis of sak1+ (suppressor of A-kinase) reveals that it functions downstream of cyclic AMP-dependent protein kinase to allow cells to exist the mitotic cycle and enter either stationary phase or the pathway leading to sexual differentiation. The sak1+ gene is essential for cell viability, and a null allele causes multiple defects in cell morphology and nuclear division. Thus, sak1+ is an important regulatory element in the life cycle of S. pombe. Sequence analysis shows that the predicted product of the sak1+ gene is an 87-kDa protein which shares homology to the RFX family of DNA-binding proteins identified in humans and mice. One member of this family, RFX1, is a transcription factor for a variety of viral and cellular genes.
Mol Cell Biol 1995 Mar
PMID:The sak1+ gene of Schizosaccharomyces pombe encodes an RFX family DNA-binding protein that positively regulates cyclic AMP-dependent protein kinase-mediated exit from the mitotic cell cycle. 786 41

Recently a novel gene containing a CAG trinucleotide repeat that is expanded on HD chromosomes has been identified(1). This gene was shown to detect a single transcript of 10-11 kb by RNA hybridization. We have however, previously identified three cDNAs which are part of the same gene that have been shown to detect two distinct transcripts of 10 kb and one that is significantly larger(2,3). These different mRNA species could be due to use of alternate transcription start sites, alternate splicing or selection of different polyadenylation sites. We have identified cDNA clones spanning the HD gene including two (HD12 and HD14) that share identical protein coding sequences but differ in size and sequence of their 3' untranslated region. HD14 has 3,360 base pairs of additional sequence distal to the previously published 3' end (1). RNA hybridization has revealed that the larger 13.7 kb fragment is the predominant transcript in human brain. cDNA fragments unique to HD14 detected only the larger transcript. Sequence analysis identified two different putative polyadenylation sequences at position 10,326 and 13,645 of the HD14 cDNA. These findings indicate that the two observed mRNA species originate from a single gene and that differential polyadenylation leads to transcripts of different size. The relative increased abundance of the larger transcript in human brain may provide some insights into the mechanism by which a widely expressed gene may exert tissue specific effects.
Hum Mol Genet 1993 Oct
PMID:Differential 3' polyadenylation of the Huntington disease gene results in two mRNA species with variable tissue expression. 790 79

The genetic organization of the spoVAF-serA area of the Bacillus subtilis chromosome and its putative transcription map have been derived from analysis of the nucleotide sequence. In order to confirm this transcription map as regards size of transcripts and to determine growth conditions for their appearance, we undertook Northern hybridization analysis of total RNA from vegetatively growing and sporulating cells. Twenty-three distinct transcripts were thus identified, 14 of which were predicted from sequence analysis and nine of which were not predicted. Eight of the latter are homologous to open reading frames identified by sequence analysis but were not expected, since no obvious promoter or terminator was found in the sequence. The last unexpected transcript does not correspond to an ORF and might identify a novel gene. Three predicted transcripts were not detected. The transcripts were classified in four groups as (i) constitutive, (ii) regulated by nutritional depletion, (iii) specific for sporulation, and (iv) possibly regulated temporally. These studies demonstrate that systematic Northern analysis of a bacterial chromosome region is a useful complement to sequence analysis.
Mol Microbiol 1993 Oct
PMID:The transcriptional organization of the Bacillus subtilis 168 chromosome region between the spoVAF and serA genetic loci. 793 30

To study the regulation and chromosomal basis of X chromosome inactivation, we have physically characterized the region in Xq13.2 known to contain the X inactivation center (XIC), a locus required in cis for inactivation to occur. Here, we report a novel gene isolated by positional cloning in this region. The gene (previously identified as DXS128E) encodes a predicted 67 kDa protein containing twelve hydrophobic transmembrane domains, characteristic of a family of transporter proteins. Presence of an N-terminal PEST domain, consisting mainly of proline/glutamic acid repeats, suggests that the protein may be rapidly or conditionally degraded. We designate this gene XPCT for X-linked PEST-containing transporter. Expression studies suggest that XPCT is subject to X chromosome inactivation, being expressed only from the active X, despite mapping within 600 kb of the XIST gene which is expressed exclusively from the inactive X. Thus, a chromosomal switch in inactivation pattern occurs between these two genes on the X chromosome.
Hum Mol Genet 1994 Jul
PMID:A novel transmembrane transporter encoded by the XPCT gene in Xq13.2. 798 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>