Clustal Omega for making accurate alignments of many protein sequences

Sievers, Fabian; Higgins, Desmond G.

doi:10.1002/pro.3290

“…Given the potential of F‐utrophin to contribute to regeneration/sarcolemmal stabilization of mdx skeletal muscle, we sought to identify where resultant protein is localised, particularly as prior studies indicate that total utrophin can be accounted for by A‐utrophin and ‐B only . Although not shared by a common utrophin isoform, we confirmed the putative N‐terminal peptide encoded by exon 1F is wholly discrete from A‐utrophin and ‐B using multiple sequence alignment and phylogenetic analysis (; Fig. 8A) prior to raising a rabbit polyclonal antibody to the predicted N terminus of mouse F‐utrophin (‘utroF’).…”

Section: Resultsmentioning

confidence: 77%

Alternative utrophin mRNAs contribute to phenotypic differences between dystrophin‐deficient mice and Duchenne muscular dystrophy

Perkins

¹

,

Davies

²

2018

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Duchenne muscular dystrophy (DMD) is a fatal disorder caused by absence of functional dystrophin protein. Compensation in dystrophin‐deficient (mdx) mice may be achieved by overexpression of its fetal paralogue, utrophin. Strategies to increase utrophin levels by stimulating promoter activity using small compounds are therefore a promising pharmacological approach. Here, we characterise similarities and differences existing within the mouse and human utrophin locus to assist in high‐throughput screening for potential utrophin modulator drugs. We identified five novel 5′‐utrophin isoforms (A′,B′,C,D and F) in adult and embryonic tissue. As the more efficient utrophin‐based response in mdx skeletal muscle appears to involve independent transcriptional activation of conserved, myogenic isoforms (A′ and F), elevating their paralogues in DMD patients is an encouraging therapeutic strategy.

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“…Transmembrane domains and overall topology were predicted with Aramemnon (Schwacke & Flügge, ). Amino acid sequences were aligned using Clustal Omega 1.2.4 and default settings (Sievers & Higgins, ). Percent identity and similarity were calculated as number of identical or similar residues in the alignment divided by the total number of positions in the alignment, including gaps.…”

Section: Methodsmentioning

confidence: 99%

Genetic and physical interactions between the organellar mechanosensitive ion channel homologs MSL1, MSL2, and MSL3 reveal a role for inter‐organellar communication in plant development

Lee

¹

,

Wilson

²

,

Richardson

³

et al. 2019

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Plant development requires communication on many levels, including between cells and between organelles within a cell. For example, mitochondria and plastids have been proposed to be sensors of environmental stress and to coordinate their responses. Here we present evidence for communication between mitochondria and chloroplasts during leaf and root development, based on genetic and physical interactions between three M echanosensitive channel of S mall conductance‐ L ike ( MSL ) proteins from Arabidopsis thaliana . MSL proteins are Arabidopsis homologs of the bacterial M echano s ensitive c hannel of S mall conductance (MscS), which relieves cellular osmotic pressure to protect against lysis during hypoosmotic shock. MSL 1 localizes to the inner mitochondrial membrane, while MSL 2 and MSL 3 localize to the inner plastid membrane and are required to maintain plastid osmotic homeostasis during normal growth and development. In this study, we characterized the phenotypic effect of a genetic lesion in MSL 1 , both in wild type and in msl2 msl3 mutant backgrounds. msl1 single mutants appear wild type for all phenotypes examined. The characteristic leaf rumpling in msl2 msl3 double mutants was exacerbated in the msl1 msl2 msl3 triple mutant. However, the introduction of the msl1 lesion into the msl2 msl3 mutant background suppressed other msl2 msl3 mutant phenotypes, including ectopic callus formation, accumulation of superoxide and hydrogen peroxide in the shoot apical meristem, decreased root length, and reduced number of lateral roots. All these phenotypes could be recovered by molecular complementation with a transgene containing a wild type version of MSL 1 . In yeast‐based interaction studies, MSL 1 interacted with itself, but not with MSL 2 or MSL 3. These results establish that the abnormalities observed in msl2 msl3 double mutants is partially dependent on the presence of functional MSL 1 and suggest a possible role for communication between plastid and mitochondria in seedling development.

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“…Protein sequences were aligned using ClustalW and the effect of mutations predicted using MutationTaster (http://www.mutationtaster.org/). …”

Section: Methodsmentioning

confidence: 99%

An N-Ethyl-N-Nitrosourea (ENU)-Induced Tyr265Stop Mutation of the DNA Polymerase Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in Mice

Gorvin

¹

,

Ahmad

²

,

Stechman

³

et al. 2018

Journal of Bone and Mineral Research

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Renal calcification (RCALC) resulting in nephrolithiasis and nephrocalcinosis, which affects ∼10% of adults by 70 years of age, involves environmental and genetic etiologies. Thus, nephrolithiasis and nephrocalcinosis occurs as an inherited disorder in ∼65% of patients, and may be associated with endocrine and metabolic disorders including: primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, and hyperoxaluria. Investigations of families with nephrolithiasis and nephrocalcinosis have identified some causative genes, but further progress is limited as large families are unavailable for genetic studies. We therefore embarked on establishing mouse models for hereditary nephrolithiasis and nephrocalcinosis by performing abdominal X‐rays to identify renal opacities in N‐ethyl‐N‐nitrosourea (ENU)‐mutagenized mice. This identified a mouse with RCALC inherited as an autosomal dominant trait, designated RCALC type 2 (RCALC2). Genomewide mapping located the Rcalc2 locus to a ∼16‐Mbp region on chromosome 11D‐E2 and whole‐exome sequence analysis identified a heterozygous mutation in the DNA polymerase gamma‐2, accessory subunit ( Polg2 ) resulting in a nonsense mutation, Tyr265Stop (Y265X), which co‐segregated with RCALC2. Kidneys of mutant mice ( Polg2 + / Y265X ) had lower POLG2 mRNA and protein expression, compared to wild‐type littermates ( Polg2 +/+ ). The Polg2 +/Y265X and Polg2 + / + mice had similar plasma concentrations of sodium, potassium, calcium, phosphate, chloride, urea, creatinine, glucose, and alkaline phosphatase activity; and similar urinary fractional excretion of calcium, phosphate, oxalate, and protein. Polg2 encodes the minor subunit of the mitochondrial DNA (mtDNA) polymerase and the mtDNA content in Polg2 + / Y265X kidneys was reduced compared to Polg2 +/+ mice, and cDNA expression profiling revealed differential expression of 26 genes involved in several biological processes including mitochondrial DNA function, apoptosis, and ubiquitination, the complement pathway, and inflammatory pathways. In addition, plasma of Polg2 + / Y265X mice, compared to Polg2 + / + littermates had higher levels of reactive oxygen species. Thus, our studies have identified a mutant mouse model for inherited renal calcification associated with a Polg2 nonsense mutation. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

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Clustal Omega for making accurate alignments of many protein sequences

Cited by 1,441 publications

References 24 publications

Alternative utrophin mRNAs contribute to phenotypic differences between dystrophin‐deficient mice and Duchenne muscular dystrophy

Alternative utrophin mRNAs contribute to phenotypic differences between dystrophin‐deficient mice and Duchenne muscular dystrophy

Genetic and physical interactions between the organellar mechanosensitive ion channel homologs MSL1, MSL2, and MSL3 reveal a role for inter‐organellar communication in plant development

An N-Ethyl-N-Nitrosourea (ENU)-Induced Tyr265Stop Mutation of the DNA Polymerase Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in Mice

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