Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the mei3 gene is sufficient to induce meiosis in the fission yeast Schizosaccharomyces pombe. The mei3 gene is located 0.64 Mb from the telomere of the left arm of Sz. pombe chromosome II. We have sequenced and analysed 107 kb of DNA from the mei3 genomic region. The sequence includes 14 known genes (bag1-B, csh3, dps1, gpt1, mei3, mfm3, pac1, prp31, rpl38-1, rpn3, rti1, spa1, spm1 and ubc4) and 26 other open reading frames (ORFs) longer than 100 codons: a density of one protein-coding gene per 2.7 kb. Twenty-one of the 40 ORFs (53%) have introns. In addition there is one lone Tf1 transposon long terminal repeat (LTR), tRNA(Trp) and tRNA(Ser) genes and a 5S rRNA gene. 14 of the novel ORFs show sequence similarities which suggest functions of their products, including a coatomer alpha-subunit, a catechol O-methyltransferase, protein kinase, asparagine synthetase, zinc metalloprotease, acetyltransferase, phosphatidylinositol 4-kinase, inositol polyphosphate phosphatase, GTPase-activating protein, permease, pre-mRNA splicing factor, 20S proteasome component and a thioredoxin-like protein. One predicted protein has similarity to the human Cockayne syndrome protein CSA and one with human GTPase XPA binding protein XAB1. Three ORFs are likely to code for proteins because they have sequence similarity with hypothetical proteins, three encode predicted coiled-coil proteins and four are sequence orphans.
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PMID:The mei3 region of the Schizosaccharomyces pombe genome. 1192 Nov

Plasmodium falciparum malaria is a major human health scourge and a key cause of mortality. Its pathogenicity partly results from the phenomenon of "cytoadherence" mediated by the PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) family. Extracellular domains of PfEMP1s are variable and bind various host endothelial receptors, whereas their cytoplasmic domains (VARCs) are relatively conserved. VARCs affix PfEMP1s in the human erythrocyte membrane by interacting with host cytoskeleton proteins and exported parasite proteins. Here, we provide in vitro and in vivo evidence for PfEMP1 phosphorylation (on VARC) and propose an important function for this modification. Specific inhibitors and enhancers have been used to identify erythrocytic casein kinase II (CKII) as the enzyme responsible for VARC modification activity. We have also delineated probable CKII target residues on VARC, which mainly reside in an N-terminal acidic cluster. Our data show that VARC phosphorylation alters its binding to parasite encoded knob-associated histidine-rich protein (KAHRP). Finally, we demonstrate reduced cytoadherence of infected RBCs to endothelial receptors like ICAM-1 and CSA (these contribute to cerebral and placental malaria, respectively) in response to their CKII inhibition. Collectively, this study furthers our understanding of VARC function, underscores the importance of erythrocytic CKII in cytoadherence, and suggests a possible new target for anti-cytoadherence molecules.
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PMID:Erythrocytic casein kinase II regulates cytoadherence of Plasmodium falciparum-infected red blood cells. 1913 28

The COP9/signalosome (CSN) multi-protein complex regulates the activity of cullin-RING ubiquitin ligases (CRLs), including the DDB2 and CSA CRL4 ligases (CRL4DDB2 and CRL4CSA), which are involved in the repair of UV-induced DNA damages. In the present study, we demonstrated that the protein kinase ATM, a key component of the DNA damage response (DDR), phosphorylates CSN1 and CSN7a, two subunits of the CSN complex, in a UV-dependent manner. The phosphorylation of CSN1 on serine 474 was detected as early as 3 h after UV-exposure, peaked at 8 h and persisted until 48 h post-UV irradiation. Such a time course suggests a role in late DDR rather than in DNA repair. Consistently, overexpression of a phosphorylation-resistant S474A CSN1 mutant reduced UV-induced apoptosis. Thus, CSN1 appears to play a role not only in DNA repair but also in UV-induced apoptosis.
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PMID:UV-dependent phosphorylation of COP9/signalosome in UV-induced apoptosis. 2698 8