Genome-wide analysis of SPAK/OSR1 binding motifs

Based on the alignment of 12 sequences of protein motifs that interact with the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress response 1), we performed genome-wide searches of the sequence [S/G/V]RF x[V/I]xx[V/I/T/S]xx, where x represents any amino acid. The “Mus musculus” search resulted in the identification of 131 mouse proteins containing 137 SPAK/OSR1 putative binding motifs. Similar numbers were found for human, zebrafish, fruit fly, and worm. A little more than half of the mouse proteins containing SPAK/OSR1 binding domains (53%) were also identified in the human search, whereas ∼17–18% of these common hits were identified in the zebrafish search. The mouse proteins could be divided into two broad categories: 2/3 had an identified function, whereas 1/3 were either predicted or of unknown function. The known proteins were grouped as transport proteins, other membrane proteins, kinases, phosphatases, cytoskeletal, ribosomal, nuclear, enzymes, and others. Analysis of the location of the SPAK/OSR1 binding motif within the protein sequence revealed distribution throughout the entire length, but with preference to the extreme amino- or carboxyl termini for a large number of proteins. Analysis of the amino acid composition of the motifs revealed a preponderance of serine residues at positions 5, 6, 7, and 8. In summary, our new search found and thus confirms the 12 proteins previously shown to interact with the kinases and identifies 119 potential new targets for SPAK and OSR1 in the mouse proteome.

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PGC7 suppresses TET3 for protecting DNA methylation

Nucleic Acids Research ◽

10.1093/nar/gkt1261 ◽

2013 ◽

Vol 42 (5) ◽

pp. 2893-2905 ◽

Cited By ~ 39

Author(s):

Chunjing Bian ◽

Xiaochun Yu

Keyword(s):

Dna Methylation ◽

Molecular Mechanism ◽

Biological Process ◽

Cpg Islands ◽

Binding Motifs ◽

Genome Wide Analysis ◽

Dna Motif ◽

Genome Wide

Abstract Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.

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Ecdysozoan Clade Rejected by Genome-Wide Analysis of Rare Amino Acid Replacements

Molecular Biology and Evolution ◽

10.1093/molbev/msm029 ◽

2007 ◽

Vol 24 (4) ◽

pp. 1080-1090 ◽

Cited By ~ 28

Author(s):

I. B. Rogozin ◽

Y. I. Wolf ◽

L. Carmel ◽

E. V. Koonin

Keyword(s):

Amino Acid ◽

Genome Wide Analysis ◽

Genome Wide

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Homoplasy in genome-wide analysis of rare amino acid replacements: the molecular-evolutionary basis for Vavilov's law of homologous series

Biology Direct ◽

10.1186/1745-6150-3-7 ◽

2008 ◽

Vol 3 (1) ◽

pp. 7 ◽

Cited By ~ 35

Author(s):

Igor B Rogozin ◽

Karen Thomson ◽

Miklos Csuros ◽

Liran Carmel ◽

Eugene V Koonin

Keyword(s):

Amino Acid ◽

Homologous Series ◽

Genome Wide Analysis ◽

Genome Wide

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Nucleocapsid and Matrix Protein Contributions to Selective Human Immunodeficiency Virus Type 1 Genomic RNA Packaging

Journal of Virology ◽

10.1128/jvi.72.3.1983-1993.1998 ◽

1998 ◽

Vol 72 (3) ◽

pp. 1983-1993 ◽

Cited By ~ 41

Author(s):

Dexter T. K. Poon ◽

Guangde Li ◽

Anna Aldovini

Keyword(s):

Human Immunodeficiency Virus ◽

Amino Acid ◽

Matrix Protein ◽

Zinc Binding ◽

Genomic Rna ◽

Rna Packaging ◽

Binding Motifs ◽

Binding Domains ◽

Immunodeficiency Virus

ABSTRACT The nucleocapsid protein (NC) of retroviruses plays a major role in genomic RNA packaging, and some evidence has implicated the matrix protein (MA) of certain retroviruses in viral RNA binding. To further investigate the role of NC in the selective recognition of genomic viral RNA and to address the potential contribution of MA in this process, we constructed chimeric and deletion human immunodeficiency virus type 1 (HIV-1) mutants that alter the NC or MA protein. Both HIV and mouse mammary tumor virus (MMTV) NC proteins have two zinc-binding domains and similar basic amino acid compositions but differ substantially in total length, amino acid sequence, and spacing of the zinc-binding motifs. When the entire NC coding sequence of HIV was replaced with the MMTV NC coding sequence, we found that the HIV genome was incorporated into virions at 50% of wild-type levels. Viruses produced from chimeric HIV genomes with complete NC replacements, or with the two NC zinc-binding domains replaced with MMTV sequences, preferentially incorporated HIV genomes when both HIV and MMTV genomes were simultaneously present in the cell. Viruses produced from chimeric MMTV genomes in which the MMTV NC had been replaced with HIV NC preferentially incorporated MMTV genomes when both HIV and MMTV genomes were simultaneously present in the cell. In contrast, viruses produced from chimeric HIV genomes containing the Moloney NC, which contains a single zinc-binding motif, were previously shown to preferentially incorporate Moloney genomic RNA. Taken together, these results indicate that an NC protein with two zinc-binding motifs is required for specific HIV RNA packaging and that the amino acid context of these motifs, while contributing to the process, is less crucial for specificity. The data also suggest that HIV NC may not be the exclusive determinant of RNA selectivity. Analysis of an HIV MA mutant revealed that specific RNA packaging does not require MA protein.

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Genome-wide analysis of Fragaria vesca three-amino-acid-loop-extension (TALE) genes

Tarla Bitkileri Merkez Arastirma Enstitusu ◽

10.38042/biotechstudies.977788 ◽

2021 ◽

Vol 30 (2) ◽

pp. 72-86

Author(s):

Gizem KABAK ◽

Seray ŞEHSUVAR ◽

Sıla TURGUT ◽

Şeyma GÖKDEMİR

Keyword(s):

Amino Acid ◽

Fragaria Vesca ◽

Genome Wide Analysis ◽

Genome Wide

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Sequence Motifs and Antimotifs in β-Barrel Membrane Proteins from a Genome-Wide Analysis: The Ala-Tyr Dichotomy and Chaperone Binding Motifs

Journal of Molecular Biology ◽

10.1016/j.jmb.2006.07.095 ◽

2006 ◽

Vol 363 (2) ◽

pp. 611-623 ◽

Cited By ~ 19

Author(s):

Ronald Jackups ◽

Sarah Cheng ◽

Jie Liang

Keyword(s):

Membrane Proteins ◽

Sequence Motifs ◽

Binding Motifs ◽

Genome Wide Analysis ◽

Genome Wide ◽

A Genome ◽

Chaperone Binding

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Calmodulation meta-analysis: Predicting calmodulin binding via canonical motif clustering

The Journal of General Physiology ◽

10.1085/jgp.201311140 ◽

2014 ◽

Vol 144 (1) ◽

pp. 105-114 ◽

Cited By ~ 42

Author(s):

Karen Mruk ◽

Brian M. Farley ◽

Alan W. Ritacco ◽

William R. Kobertz

Keyword(s):

Membrane Transport ◽

Calcium Binding ◽

Meta Analysis ◽

Data Bank ◽

Transport Proteins ◽

Binding Motifs ◽

Calmodulin Binding ◽

Binding Domains ◽

Membrane Transport Proteins ◽

Target Sequences

The calcium-binding protein calmodulin (CaM) directly binds to membrane transport proteins to modulate their function in response to changes in intracellular calcium concentrations. Because CaM recognizes and binds to a wide variety of target sequences, identifying CaM-binding sites is difficult, requiring intensive sequence gazing and extensive biochemical analysis. Here, we describe a straightforward computational script that rapidly identifies canonical CaM-binding motifs within an amino acid sequence. Analysis of the target sequences from high resolution CaM–peptide structures using this script revealed that CaM often binds to sequences that have multiple overlapping canonical CaM-binding motifs. The addition of a positive charge discriminator to this meta-analysis resulted in a tool that identifies potential CaM-binding domains within a given sequence. To allow users to search for CaM-binding motifs within a protein of interest, perform the meta-analysis, and then compare the results to target peptide–CaM structures deposited in the Protein Data Bank, we created a website and online database. The availability of these tools and analyses will facilitate the design of CaM-related studies of ion channels and membrane transport proteins.

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Neural network modeling of differential binding between wild-type and mutant CTCF reveals putative binding preferences for zinc fingers 1-2

10.1101/2021.09.23.461552 ◽

2021 ◽

Author(s):

Irene Miriam Kaplow ◽

Abhimanyu Banerjee ◽

Chuan-Sheng Foo

Keyword(s):

Neural Network ◽

Dna Binding ◽

Zinc Fingers ◽

Neural Network Modeling ◽

Binding Motif ◽

Wild Type ◽

Core Motif ◽

Binding Motifs ◽

Binding Domains

Background: Many transcription factors (TFs), such as multi zinc-finger (ZF) TFs, have multiple DNA binding domains (DBDs) with multiple components, and deciphering the DNA binding motifs of individual components is a major challenge. One example of such a TF is CCCTC-binding factor (CTCF), a TF with eleven ZFs that plays a variety of roles in transcriptional regulation, most notably anchoring DNA loops. Previous studies found that CTCF zinc fingers (ZFs) 3-7 bind CTCF's core motif and ZFs 9-11 bind a specific upstream motif, but the motifs of ZFs 1-2 have yet to be identified. Results: We developed a new approach to identifying the binding motifs of individual DBDs of a TF through analyzing chromatin immunoprecipitation sequencing (ChIP-seq) experiments in which a single DBD is mutated: we train a deep convolutional neural network to predict whether wild-type TF binding sites are preserved in the mutant TF dataset and interpret the model. We applied this approach to mouse CTCF ChIP-seq data and, in addition to identifying the known binding preferences of CTCF ZFs 3-11, we identified a GAG binding motif for ZF1 and a weak ATT binding motif for ZF2. We analyzed other CTCF datasets to provide additional evidence that ZFs 1-2 interact with the motifs we identified, and we found that the presence of the motif for ZF1 is associated with Ctcf peak strength. Conclusions: Our approach can be applied to any TF for which in vivo binding data from both the wild-type and mutated versions of the TF are available, and our findings provide an unprecedently comprehensive understanding of the binding preferences of CTCF's DBDs.

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Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1610611114 ◽

2017 ◽

Vol 114 (23) ◽

pp. 5854-5861 ◽

Cited By ~ 14

Author(s):

Gregory A. Cary ◽

Alys M. Cheatle Jarvela ◽

Rene D. Francolini ◽

Veronica F. Hinman

Keyword(s):

Transcription Factor ◽

Sea Urchins ◽

Transcription Factor Binding ◽

Model Systems ◽

Binding Motif ◽

Regulatory Sequences ◽

Binding Motifs ◽

Chip Sequencing ◽

Factor Binding ◽

Genome Wide

Sea stars and sea urchins are model systems for interrogating the types of deep evolutionary changes that have restructured developmental gene regulatory networks (GRNs). Although cis-regulatory DNA evolution is likely the predominant mechanism of change, it was recently shown that Tbrain, a Tbox transcription factor protein, has evolved a changed preference for a low-affinity, secondary binding motif. The primary, high-affinity motif is conserved. To date, however, no genome-wide comparisons have been performed to provide an unbiased assessment of the evolution of GRNs between these taxa, and no study has attempted to determine the interplay between transcription factor binding motif evolution and GRN topology. The study here measures genome-wide binding of Tbrain orthologs by using ChIP-sequencing and associates these orthologs with putative target genes to assess global function. Targets of both factors are enriched for other regulatory genes, although nonoverlapping sets of functional enrichments in the two datasets suggest a much diverged function. The number of low-affinity binding motifs is significantly depressed in sea urchins compared with sea star, but both motif types are associated with genes from a range of functional categories. Only a small fraction (∼10%) of genes are predicted to be orthologous targets. Collectively, these data indicate that Tbr has evolved significantly different developmental roles in these echinoderms and that the targets and the binding motifs in associated cis-regulatory sequences are dispersed throughout the hierarchy of the GRN, rather than being biased toward terminal process or discrete functional blocks, which suggests extensive evolutionary tinkering.

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