TY - Generic T1 - Developmental expression of chicken FOXN1 and putative target genes during feather development. Y1 - 2014 A1 - Darnell, Diana K A1 - Zhang, Li S A1 - Hannenhalli, Sridhar A1 - Yaklichkin, Sergey Y KW - Amino Acid Sequence KW - Animals KW - Biological Evolution KW - Blotting, Western KW - Cell Differentiation KW - Cells, Cultured KW - Chick Embryo KW - Chickens KW - Cloning, Molecular KW - Embryo, Nonmammalian KW - Epidermis KW - Feathers KW - Forkhead Transcription Factors KW - Gene Expression Regulation, Developmental KW - In Situ Hybridization KW - Molecular Sequence Data KW - Morphogenesis KW - Phylogeny KW - Real-Time Polymerase Chain Reaction KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger KW - Sequence Homology, Amino Acid AB -

FOXN1 is a member of the forkhead box family of transcription factors. FOXN1 is crucial for hair outgrowth and thymus differentiation in mammals. Unlike the thymus, which is found in all amniotes, hair is an epidermal appendage that arose after the last shared common ancestor between mammals and birds, and hair and feathers differ markedly in their differentiation and gene expression. Here, we show that FOXN1 is expressed in embryonic chicken feathers, nails and thymus, demonstrating an evolutionary conservation that goes beyond obvious homology. At embryonic day (ED) 12, FOXN1 is expressed in some feather buds and at ED13 expression extends along the length of the feather filament. At ED14 FOXN1 mRNA is restricted to the proximal feather filament and is not detectable in distal feather shafts. At the base of the feather, FOXN1 is expressed in the epithelium of the feather sheath and distal barb and marginal plate, whereas in the midsection FOXN1 transcripts are mainly detected in the barb plates of the feather filament. FOXN1 is also expressed in claws; however, no expression was detected in skin or scales. Despite expression of FOXN1 in developing feathers, examination of chick homologs of five putative mammalian FOXN1 target genes shows that, while these genes are expressed in feathers, there is little similarity to the FOXN1 expression pattern, suggesting that some gene regulatory networks may have diverged during evolution of epidermal appendages.

JA - Int J Dev Biol VL - 58 CP - 1 M3 - 10.1387/ijdb.130023sy ER - TY - Generic T1 - Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P. Y1 - 2012 A1 - Waisberg, Michael A1 - Cerqueira, Gustavo C A1 - Yager, Stephanie B A1 - Francischetti, Ivo M B A1 - Lu, Jinghua A1 - Gera, Nidhi A1 - Srinivasan, Prakash A1 - Miura, Kazutoyo A1 - Rada, Balazs A1 - Lukszo, Jan A1 - Barbian, Kent D A1 - Leto, Thomas L A1 - Porcella, Stephen F A1 - Narum, David L A1 - El-Sayed, Najib A1 - Miller, Louis H A1 - Pierce, Susan K KW - Amino Acid Sequence KW - Animals KW - Calcium-Binding Proteins KW - Chromatography, Gel KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme-Linked Immunosorbent Assay KW - HUMANS KW - Merozoite Surface Protein 1 KW - Microscopy, Confocal KW - Molecular Sequence Data KW - Neoplasm Proteins KW - Plasmodium falciparum KW - Sequence Homology, Amino Acid KW - Surface Plasmon Resonance AB -

The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.

JA - Proc Natl Acad Sci U S A VL - 109 CP - 14 M3 - 10.1073/pnas.1202689109 ER - TY - JOUR T1 - Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region. JF - BMC Genomics Y1 - 2006 A1 - Westenberger, Scott J A1 - Cerqueira, Gustavo C A1 - El-Sayed, Najib M A1 - Zingales, Bianca A1 - Campbell, David A A1 - Sturm, Nancy R KW - Amino Acid Sequence KW - Animals KW - Animals, Inbred Strains KW - Base Composition KW - Conserved Sequence KW - DNA, Kinetoplast KW - Frameshifting, Ribosomal KW - Gene Deletion KW - Gene Order KW - Genetic Variation KW - Leishmania KW - Models, Biological KW - Molecular Sequence Data KW - Muscle Proteins KW - NADH Dehydrogenase KW - Open Reading Frames KW - Regulatory Elements, Transcriptional KW - RNA Editing KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Ubiquitin-Protein Ligases KW - Untranslated Regions AB -

BACKGROUND: The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.

RESULTS: We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5'-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.

CONCLUSION: The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network.

VL - 7 M3 - 10.1186/1471-2164-7-60 ER - TY - JOUR T1 - Telomere and subtelomere of Trypanosoma cruzi chromosomes are enriched in (pseudo)genes of retrotransposon hot spot and trans-sialidase-like gene families: the origins of T. cruzi telomeres. JF - Gene Y1 - 2005 A1 - Kim, Dong A1 - Chiurillo, Miguel Angel A1 - El-Sayed, Najib A1 - Jones, Kristin A1 - Santos, Márcia R M A1 - Porcile, Patricio E A1 - Andersson, Björn A1 - Myler, Peter A1 - da Silveira, Jose Franco A1 - Ramírez, José Luis KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Chromosomes KW - Chromosomes, Artificial, Bacterial KW - DNA, Protozoan KW - Genes, Protozoan KW - Glycoproteins KW - Molecular Sequence Data KW - Multigene Family KW - Neuraminidase KW - Pseudogenes KW - Retroelements KW - Sequence Homology, Amino Acid KW - Sequence Homology, Nucleic Acid KW - Telomere KW - Trypanosoma cruzi AB -

Here, we sequenced two large telomeric regions obtained from the pathogen protozoan Trypanosoma cruzi. These sequences, together with in silico assembled contigs, allowed us to establish the general features of telomeres and subtelomeres of this parasite. Our findings can be summarized as follows: We confirmed the presence of two types of telomeric ends; subtelomeric regions appeared to be enriched in (pseudo)genes of RHS (retrotransposon hot spot), TS (trans-sialidase)-like proteins, and putative surface protein DGF-1 (dispersed gene family-1). Sequence analysis of the ts-like genes located at the telomeres suggested that T. cruzi chromosomal ends could have been the site for generation of new gp85 variants, an important adhesin molecule involved in the invasion of mammalian cells by T. cruzi. Finally, a mechanism for generation of T. cruzi telomere by chromosome breakage and telomere healing is proposed.

VL - 346 M3 - 10.1016/j.gene.2004.10.014 ER - TY - JOUR T1 - Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2004 A1 - Seshadri, Rekha A1 - Myers, Garry S. A. A1 - Tettelin, Hervé A1 - Eisen, Jonathan A. A1 - Heidelberg, John F. A1 - Dodson, Robert J. A1 - Davidsen, Tanja M. A1 - DeBoy, Robert T. A1 - Fouts, Derrick E. A1 - Haft, Dan H. A1 - J. Selengut A1 - Ren, Qinghu A1 - Brinkac, Lauren M. A1 - Madupu, Ramana A1 - Kolonay, Jamie A1 - Durkin, A. Scott A1 - Daugherty, Sean C. A1 - Shetty, Jyoti A1 - Shvartsbeyn, Alla A1 - Gebregeorgis, Elizabeth A1 - Geer, Keita A1 - Tsegaye, Getahun A1 - Malek, Joel A1 - Ayodeji, Bola A1 - Shatsman, Sofiya A1 - McLeod, Michael P. A1 - Smajs, David A1 - Howell, Jerrilyn K. A1 - Pal, Sangita A1 - Amin, Anita A1 - Vashisth, Pankaj A1 - McNeill, Thomas Z. A1 - Xiang, Qin A1 - Sodergren, Erica A1 - Baca, Ernesto A1 - Weinstock, George M. A1 - Norris, Steven J. A1 - Fraser, Claire M. A1 - Paulsen, Ian T. KW - ATP-Binding Cassette Transporters KW - Bacterial Proteins KW - Base Sequence KW - Borrelia burgdorferi KW - Genes, Bacterial KW - Genome, Bacterial KW - Leptospira interrogans KW - Models, Genetic KW - Molecular Sequence Data KW - Mouth KW - Sequence Homology, Amino Acid KW - Treponema KW - Treponema pallidum AB - We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function. VL - 101 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract ER - TY - JOUR T1 - Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping. JF - Development Y1 - 2003 A1 - Nagengast, Alexis A A1 - Stitzinger, Shane M A1 - Tseng, Chin-Hsiu A1 - Mount, Stephen M A1 - Salz, Helen K KW - Alternative Splicing KW - Amino Acid Sequence KW - Animals KW - Animals, Genetically Modified KW - Drosophila melanogaster KW - Drosophila Proteins KW - Exons KW - Female KW - Gene Expression Regulation, Developmental KW - Genes, Insect KW - Homeostasis KW - Male KW - Models, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins KW - Point Mutation KW - Ribonucleoprotein, U1 Small Nuclear KW - Ribonucleoproteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Homology, Amino Acid KW - Sex Differentiation AB -

Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.

VL - 130 CP - 3 ER - TY - JOUR T1 - The TIGRFAMs database of protein families JF - Nucleic acids researchNucleic Acids Research Y1 - 2003 A1 - Haft, Daniel H. A1 - J. Selengut A1 - White, Owen KW - Animals KW - Databases, Protein KW - Markov chains KW - Mixed Function Oxygenases KW - Phylogeny KW - Proteins KW - Pyruvate Carboxylase KW - Sequence Homology, Amino Acid AB - TIGRFAMs is a collection of manually curated protein families consisting of hidden Markov models (HMMs), multiple sequence alignments, commentary, Gene Ontology (GO) assignments, literature references and pointers to related TIGRFAMs, Pfam and InterPro models. These models are designed to support both automated and manually curated annotation of genomes. TIGRFAMs contains models of full-length proteins and shorter regions at the levels of superfamilies, subfamilies and equivalogs, where equivalogs are sets of homologous proteins conserved with respect to function since their last common ancestor. The scope of each model is set by raising or lowering cutoff scores and choosing members of the seed alignment to group proteins sharing specific function (equivalog) or more general properties. The overall goal is to provide information with maximum utility for the annotation process. TIGRFAMs is thus complementary to Pfam, whose models typically achieve broad coverage across distant homologs but end at the boundaries of conserved structural domains. The database currently contains over 1600 protein families. TIGRFAMs is available for searching or downloading at www.tigr.org/TIGRFAMs. VL - 31 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12520025?dopt=Abstract ER - TY - JOUR T1 - Evidence for a plastid origin of plant ethylene receptor genes. JF - Plant Physiol Y1 - 2002 A1 - Mount, Stephen M A1 - Chang, Caren KW - Amino Acid Sequence KW - Anabaena KW - Arabidopsis KW - Cyanobacteria KW - Molecular Sequence Data KW - Plant Proteins KW - Plastids KW - Protein Kinases KW - Receptors, Cell Surface KW - Sequence Homology, Amino Acid VL - 130 CP - 1 M3 - 10.1104/pp.005397 ER - TY - JOUR T1 - A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei. JF - Eukaryot Cell Y1 - 2002 A1 - Bringaud, Frederic A1 - Biteau, Nicolas A1 - Melville, Sara E A1 - Hez, Stéphanie A1 - El-Sayed, Najib M A1 - Leech, Vanessa A1 - Berriman, Matthew A1 - Hall, Neil A1 - Donelson, John E A1 - Baltz, Théo KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Cloning, Molecular KW - DNA Primers KW - DNA, Protozoan KW - Escherichia coli KW - Genes, Protozoan KW - Molecular Sequence Data KW - Multigene Family KW - Mutagenesis, Insertional KW - Phylogeny KW - Polymorphism, Genetic KW - Protozoan Proteins KW - Pseudogenes KW - Retroelements KW - sequence alignment KW - Sequence Homology, Amino Acid KW - Telomere KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

We describe a novel gene family that forms clusters in subtelomeric regions of Trypanosoma brucei chromosomes and partially accounts for the observed clustering of retrotransposons. The ingi and ribosomal inserted mobile element (RIME) non-LTR retrotransposons share 250 bp at both extremities and are the most abundant putatively mobile elements, with about 500 copies per haploid genome. From cDNA clones and subsequently in the T. brucei genomic DNA databases, we identified 52 homologous gene and pseudogene sequences, 16 of which contain a RIME and/or ingi retrotransposon inserted at exactly the same relative position. Here these genes are called the RHS family, for retrotransposon hot spot. Comparison of the protein sequences encoded by RHS genes (21 copies) and pseudogenes (24 copies) revealed a conserved central region containing an ATP/GTP-binding motif and the RIME/ingi insertion site. The RHS proteins share between 13 and 96% identity, and six subfamilies, RHS1 to RHS6, can be defined on the basis of their divergent C-terminal domains. Immunofluorescence and Western blot analyses using RHS subfamily-specific immune sera show that RHS proteins are constitutively expressed and occur mainly in the nucleus. Analysis of Genome Survey Sequence databases indicated that the Trypanosoma brucei diploid genome contains about 280 RHS (pseudo)genes. Among the 52 identified RHS (pseudo)genes, 48 copies are in three RHS clusters located in subtelomeric regions of chromosomes Ia and II and adjacent to the active bloodstream form expression site in T. brucei strain TREU927/4 GUTat10.1. RHS genes comprise the remaining sequence of the size-polymorphic "repetitive region" described for T. brucei chromosome I, and a homologous gene family is present in the Trypanosoma cruzi genome.

VL - 1 CP - 1 ER - TY - JOUR T1 - MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases JF - BiochemistryBiochemistry Y1 - 2001 A1 - J. Selengut KW - Amino Acid Motifs KW - Amino Acid Sequence KW - Animals KW - Aspartic Acid KW - Catalytic Domain KW - HUMANS KW - Hydrolases KW - Mice KW - Molecular Sequence Data KW - Multigene Family KW - Mutagenesis, Site-Directed KW - Phosphoprotein Phosphatases KW - Protein Structure, Tertiary KW - Protein Tyrosine Phosphatases KW - Rats KW - Saccharomyces cerevisiae KW - sequence alignment KW - Sequence Homology, Amino Acid AB - MDP-1 is a eukaryotic magnesium-dependent acid phosphatase with little sequence homology to previously characterized phosphatases. The presence of a conserved motif (Asp-X-Asp-X-Thr) in the N terminus of MDP-1 suggested a relationship to the haloacid dehalogenase (HAD) superfamily, which contains a number of magnesium-dependent acid phosphatases. These phosphatases utilize an aspartate nucleophile and contain a number of conserved active-site residues and hydrophobic patches, which can be plausibly aligned with conserved residues in MDP-1. Seven site-specific point mutants of MDP-1 were produced by modifying the catalytic aspartate, serine, and lysine residues to asparagine or glutamate, alanine, and arginine, respectively. The activity of these mutants confirms the assignment of MDP-1 as a member of the HAD superfamily. Detailed comparison of the sequence of the 15 MDP-1 sequences from various organisms with other HAD superfamily sequences suggests that MDP-1 is not closely related to any particular member of the superfamily. The crystal structures of several HAD family enzymes identify a domain proximal to the active site responsible for important interactions with low molecular weight substrates. The absence of this domain or any other that might perform the same function in MDP-1 suggests an "open" active site capable of interactions with large substrates such as proteins. This suggestion was experimentally confirmed by demonstration that MDP-1 is competent to catalyze the dephosphorylation of tyrosine-phosphorylated proteins. VL - 40 N1 - http://www.ncbi.nlm.nih.gov/pubmed/11601995?dopt=Abstract ER - TY - JOUR T1 - MDP-1: A novel eukaryotic magnesium-dependent phosphatase JF - BiochemistryBiochemistry Y1 - 2000 A1 - J. Selengut A1 - Levine, R. L. KW - Amino Acid Sequence KW - Animals KW - Catalysis KW - Cations KW - Chromatography, Affinity KW - Cloning, Molecular KW - Cysteine KW - Enzyme Inhibitors KW - Histidine KW - Hydrogen-Ion Concentration KW - Magnesium KW - Mice KW - Molecular Sequence Data KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 1 KW - Rabbits KW - Sequence Analysis, Protein KW - Sequence Homology, Amino Acid KW - Substrate Specificity AB - We report here the purification, cloning, expression, and characterization of a novel phosphatase, MDP-1. In the course of investigating the reported acid phosphatase activity of carbonic anhydrase III preparations, several discrete phosphatases were discerned. One of these, a magnesium-dependent species of 18.6 kDa, was purified to homogeneity and yielded several peptide sequences from which the parent gene was identified by database searching. Although orthologous genes were identified in fungi and plants as well as mammalian species, there was no apparent homology to any known family of phosphatases. The enzyme was expressed in Escherichia coli with a fusion tag and purified by affinity methods. The recombinant enzyme showed magnesium-dependent acid phosphatase activity comparable to the originally isolated rabbit protein. The enzyme catalyzes the rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or phosphothreonine is considerable, but the enzyme did not show activity toward five phosphotyrosine-containing peptides. None of the various substrates assayed (including various nucleotide, sugar, amino acid and peptide phosphates, phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM, and many showed negligible rates of hydrolysis. The enzyme is inhibited by vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest that the enzymatic mechanism is not dependent on cysteine, histidine, or nonmagnesium metal ions. In recognition of these observations, the enzyme has been given the name magnesium-dependent phosphatase-1 (MDP-1). VL - 39 N1 - http://www.ncbi.nlm.nih.gov/pubmed/10889041?dopt=Abstract ER -