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 detection of the single base pair mutations at codon 6 of the beta-globin gene is important for the prenatal diagnosis of sickle-cell anaemia and SC disease. A novel procedure has been designed to create a restriction site at both the beta A and beta C alleles to facilitate the discrimination of haemoglobins A, S and C. The general principle of this procedure is to enzymatically amplify genomic DNA using a modified primer containing an altered 3'-terminal nucleotide to create these restriction sites. After this modified primer has been efficiently incorporated into amplified DNA, the PCR products are digested with the restriction enzymes Ava I and Sty I. Ava I recognizes a site in amplified DNA containing a beta A allele, and Sty I recognizes a site in DNA containing a beta C allele. Since the beta A and beta C alleles can be distinguished directly by the presence of a restriction site, the beta S allele can be identified indirectly. All three beta-globin alleles are easily distinguished by size and pattern of electrophoresed fragments on agarose gels. This procedure is specific and sensitive, thus permitting rapid, economical diagnosis of sickle-cell anaemia and SC disease.
Mol Cell Probes 1992 Aug
PMID:Prenatal diagnosis by enzymatic amplification and restriction endonuclease digestion for detection of haemoglobins A, S and C. 132 16

We have cloned a novel kinase (STY) from an embryonal carcinoma cell line. Sequence analysis of the STY cDNA reveals that it shares sequence homology with serine/threonine-type kinases and yet the bacterial expression product of the STY cDNA appears to have serine-, threonine-, and tyrosine-phosphorylating activities. The predicted STY protein is highly basic and contains a putative nuclear localization signal. During differentiation, two new mRNAs were detected in addition to the embryonic transcript.
Mol Cell Biol 1991 Jan
PMID:STY, a tyrosine-phosphorylating enzyme with sequence homology to serine/threonine kinases. 198 48

Steroidogenic factor-1 (SF-1), an orphan receptor of the nuclear hormone receptor family, binds to the AAGGTCA motif in the promoter elements of several diverse target genes, including some that mediate steroidogenesis and sexual differentiation. In addition, SF-1 is expressed in embryonic forebrain, suggesting that it plays a role in neural development. This study was undertaken to study the distribution and regulation of SF-1 mRNA expression in the rat brain. SF-1 mRNA levels were measured in tissue dissections by ribonuclease protection assay. A 452 nt 32P-labeled cRNA probe, complementary to the putative ligand-binding domain of the rat SF-1 mRNA, was synthesized from the rat SF-1 cDNA inserted into pBluescript II KS, using a Sty 1 fragment and T3 polymerase. The probe protected a single 390 nt transcript in the medial basal hypothalamus (MBH) and peripheral steroidogenic tissues of the male rat. The size of this protected band corresponded to that of the protected sense RNA standard (HindIII fragment of the SF-1 cDNA transcribed with T7 polymerase). No SF-1 mRNA was detected in the preoptic area, amygdala or cingulate cortex. The levels of SF-1 mRNA in MBH were not affected by gonadectomy or androgen treatment, nor was there a sex difference in its expression in adults. In situ hybridization histochemistry revealed that SF-1 was localized to the ventromedial nucleus of the adult hypothalamus. The levels of SF-1 mRNA were high on gestational day 18 after which they fell by approximately 30% and remained constant throughout gestation, the first week of neonatal life, and into adulthood. These results demonstrate that the gene encoding SF-1 is expressed in a discrete region of the rat hypothalamus and appears to be developmentally regulated, but not affected by gonadal hormones in adults.
Brain Res Mol Brain Res 1997 Feb
PMID:Expression of the orphan receptor steroidogenic factor-1 mRNA in the rat medial basal hypothalamus. 903 Jun 99

The complete macronuclear DNA polymerase alpha gene, previously sequenced in Oxytricha nova, has been cloned from a genomic macronuclear library and sequenced for the hypotrich O. trifallax. Macronuclear DNA clones of DNA polymerase alpha encoding approximately 1000 amino acids, or approximately two-thirds of the open reading frame, have been obtained by PCR and sequenced for Halteria grandinella, Holosticha species, Paraurostyla viridis, Pleurotricha lanceolata, Stylonychia lemnae Teller, Sty. mytilus, Uroleptus gallina, and Urostyla grandis. Phylogenetic relationships inferred from DNA polymerase alpha amino acid sequences have been used to clarify taxonomic relationships previously determined by morphology of the cell cortex. Hypotrich phylogenies based on DNA polymerase alpha amino acid sequences are incongruent with morphological and other molecular phylogenies. Based upon these data, we assert that, contrary to morphological data, O. nova and O. trifallax are different species, and we propose that the oligotrich Halteria grandinella be reclassified as a hypotrich. This work also extends the available data base of eukaryotic DNA polymerase alpha sequences, and suggests new amino acid sequence targets for mutagenesis experiments to continue the functional dissection of DNA pol alpha biochemistry at the molecular level.
J Mol Evol 1997 Sep
PMID:Phylogenetic relationships among hypotrichous ciliates determined with the macronuclear gene encoding the large, catalytic subunit of DNA polymerase alpha. 930 25

The splicing of mammalian mRNA precursors requires both protein phosphorylation and dephosphorylation, likely involving modification of members of the SR protein family of splicing factors. Several kinases have been identified that can phosphorylate SR proteins in vitro, and transfection assays have provided evidence that at least one of these, Clk/Sty, can modulate splicing in vivo. But evidence that a specific kinase can directly affect the splicing activity of SR proteins has been lacking. Here, by using purified recombinant Clk/Sty, a catalytically inactive mutant, and individual SR proteins, we show that Clk/Sty directly affects the activity of SR proteins, but not other essential splicing factors, in reconstituted splicing assays. We also provide evidence that both hyper- and hypophosphorylation inhibit SR protein splicing activity, repressing constitutive splicing and switching alternative splice site selection. These findings indicate that Clk/Sty directly and specifically influences the activity of SR protein splicing factors and, importantly, show that both under- and overphosphorylation of SR proteins can modulate splicing.
Mol Cell Biol 1999 Oct
PMID:The protein kinase Clk/Sty directly modulates SR protein activity: both hyper- and hypophosphorylation inhibit splicing. 1049 Jun 36

The mglA gene encodes a 22 kDa GTPase that is critical for single-cell (A) gliding, type IV pili-mediated (S) gliding and development of Myxococcus xanthus. To identify components that interact with MglA to control these processes, second-site mutations that restore movement to non-motile mglA mutants were sought. An allele-specific extragenic suppressor of mglA8, named mas815 (mglA8 suppressor 15), was obtained. mas815 does not bypass the requirement for MglA, yet it restores type IV pili-mediated motility and starvation-induced development. Single-cell (A) motility is not restored. The suppressing mutation maps to the 3' end of a gene, masK, in an operon immediately upstream of the mglBA operon. masK encodes a protein of the STY kinase family. When the masK gene was used as bait against a library carrying M. xanthus DNA in the yeast two-hybrid system, eight positive, independent clones containing fusions of mglA to GAL4 were obtained, thus confirming the interaction between MglA and MasK. MasK, expressed in Escherichia coli, was shown to phosphorylate at a tyrosine residue(s). The gain-of-function in the masK815 mutant was correlated with increased production of extracellular fibrils, which are required for adhesion, cell-cell contact and sensing phosphatidylethanolamine chemoattractants. These data suggest that the interaction between MasK and MglA is an essential part of a signal transduction pathway controlling motility and development.
Mol Microbiol 2002 Dec
PMID:MglA, a small GTPase, interacts with a tyrosine kinase to control type IV pili-mediated motility and development of Myxococcus xanthus. 1245 25

SR proteins constitute a family of splicing factors that play key roles in both constitutive and regulated splicing in metazoan organisms. The proteins are extensively phosphorylated, and kinases capable of phosphorylating them have been identified. However, little is known about how these kinases function, for example, whether they target specific SR proteins or whether the kinases themselves are regulated. Here we describe properties of one such kinase, Clk/Sty, the founding member of the Clk/Sty family of dual-specificity kinases. Clk/Sty is autophosphorylated on both Ser/Thr and Thr residues, and using both direct kinase assays and SR protein-dependent splicing assays, we have analyzed the effects of each type of modification. We find not only that the pattern of phosphorylation on a specific SR protein substrate, ASF/SF2, is modulated by autophosphorylation but also that the ability of Clk/Sty to recognize different SR proteins is influenced by the extent and nature of autophosphorylation. Strikingly, phosphorylation of ASF/SF2 is sensitive to changes in Tyr, but not Ser/Thr, autophosphorylation while that of SC35 displays the opposite pattern. In contrast, phosphorylation of a third SR protein, SRp40, is unaffected by autophosphorylation. We also present biochemical data indicating that as expected for a factor directly involved in splicing control (but in contrast to recent reports), Clk/Sty is found in the nucleus of several different cell types.
Mol Cell Biol 2003 Jun
PMID:Regulation and substrate specificity of the SR protein kinase Clk/Sty. 1277 58

The arginine-serine (RS)-rich domain of the SR protein ASF/SF2 is phosphorylated by SR protein kinases (SRPKs) and Clk/Sty kinases. However, the mode of phosphorylation by these kinases and their coordination in the biological regulation of ASF/SF2 is unknown. Here, we report the crystal structure of an active fragment of human SRPK1 bound to a peptide derived from an SR protein. This structure led us to identify a docking motif in ASF/SF2. We find that this docking motif restricts phosphorylation of ASF/SF2 by SRPK1 to the N-terminal part of the RS domain - a property essential for its assembly into nuclear speckles. We further show that Clk/Sty causes release of ASF/SF2 from speckles by phosphorylating the C-terminal part of its RS domain. These results suggest that the docking motif of ASF/SF2 is a key regulatory element for sequential phosphorylation by SRPK1 and Clk/Sty and, thus, is essential for its subcellular localization.
Mol Cell 2005 Oct 07
PMID:Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. 1620 47

Reef-building corals are fundamental to the most diverse marine ecosystems, yet a detailed understanding of the processes involved in the establishment, persistence and ecology of the coral-dinoflagellate association remains largely unknown. This study explores symbiont diversity in relation to habitat by employing a broad-scale sampling regime using ITS2 and denaturing gradient gel electrophoresis. Samples from Pocillopora damicornis, Stylophora pistillata and Seriatopora hystrix all harboured host-specific clade C symbiont types at Heron Island (Great Barrier Reef, Australia). While Ser. hystrix associated with a single symbiont profile along its entire depth distribution, both P. damicornis and Sty. pistillata associated with multiple symbiont profiles that showed a strong zonation with depth. It is shown that, with an increased sampling effort, previously identified 'rare' symbiont types within this group of host species are in fact environmental specialists. A multivariate approach was used to expand on the common distinction of symbionts by a single genetic identity. It shows merit in its capacity not only to include all the variability present within the marker region but also to reliably represent ecological diversification of symbionts. Furthermore, the cohesive species concept is explored to explain how niche partitioning may drive diversification of closely related symbiont lineages. This study provides thus evidence that closely related symbionts are ecologically distinct and fulfil their own niche within the ecosystem provided by the host and external environment.
Mol Ecol 2007 Sep
PMID:Niche partitioning of closely related symbiotic dinoflagellates. 1784 44

SR proteins are essential splicing factors whose function is controlled by multi-site phosphorylation of a C-terminal domain rich in arginine-serine repeats (RS domain). The protein kinase SRPK1 has been shown to polyphosphorylate the N-terminal portion of the RS domain (RS1) of the SR protein ASF/SF2, a modification that promotes nuclear entry of this splicing factor and engagement in splicing function. Later, dephosphorylation is required for maturation of the spliceosome and other RNA processing steps. While phosphates are attached to RS1 in a sequential manner by SRPK1, little is known about how they are removed. To investigate factors that control dephosphorylation, we monitored region-specific mapping of phosphorylation sites in ASF/SF2 as a function of the protein phosphatase PP1. We showed that 10 phosphates added to the RS1 segment by SRPK1 are removed in a preferred N-to-C manner, directly opposing the C-to-N phosphorylation by SRPK1. Two N-terminal RNA recognition motifs in ASF/SF2 control access to the RS domain and guide the directional mechanism. Binding of RNA to the RNA recognition motifs protects against dephosphorylation, suggesting that engagement of the SR protein with exonic splicing enhancers can regulate phosphoryl content in the RS domain. In addition to regulation by N-terminal domains, phosphorylation of the C-terminal portion of the RS domain (RS2) by the nuclear protein kinase Clk/Sty inhibits RS1 dephosphorylation and disrupts the directional mechanism. The data indicate that both RNA-protein interactions and phosphorylation in flanking sequences induce conformations of ASF/SF2 that increase the lifetime of phosphates in the RS domain.
J Mol Biol 2010 Oct 29
PMID:Mechanism of dephosphorylation of the SR protein ASF/SF2 by protein phosphatase 1. 2082 66


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