The Universal Protein Resource (UniProt): an expanding universe of protein information

Wu, Cathy H.; Apweiler, Rolf; Bairoch, Amos Marc; Natale, Darren A.; Barker, Winona C.; Boeckmann, Brigitte; Ferro, Serenella; Gasteiger, Elisabeth; Huang, Hongzhan; López, Rodrigo; Magrane, Michele; Martin, Maria Jesus; Mazumder, Raja; O′Donovan, Claire; Redaschi, Nicole; Süzek, Barış E.

doi:10.1093/nar/gkj161

Cited by 989 publications

(821 citation statements)

References 22 publications

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“…Candidate proteins from the high stringency threshold include HERC4, a probable E3 ubiquitin-protein ligase by sequence similarity (Wu et al 2006), and NUP85, a component of the nuclear pore complex thought to play a role in phosphatidyl-inositol-3-kinase-dependent pathways (Terashima et al 2005). CAPNS1, scoring 4.0 (rank 7; moderate), belongs to a well-conserved family of calcium-dependent, cysteine proteases whose link to cellular senescence and DNA damage response has been studied (Demarchi and Schneider 2007).…”

Section: Discussionmentioning

confidence: 99%

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Magalhães

2011

AGE

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The genetic basis of the large species differences in longevity and aging remains a mystery. Thanks to recent large-scale genome sequencing efforts, the genomes of multiple species have been sequenced and can be used for cross-species comparisons to study species divergence in longevity. By analyzing proteins under accelerated evolution in several mammalian lineages where maximum lifespan increased, we identified genes and processes that are candidate targets of selection when longevity evolves. We identified several proteins with longevity-specific selection patterns, including COL3A1 that has previously been related to aging and proteins related to DNA damage repair and response such as DDB1 and CAPNS1. Moreover, we found that processes such as lipid metabolism and cholesterol catabolism show such patterns of selection and suggest a link between the evolution of lipid metabolism, cholesterol catabolism, and the evolution of longevity. Lastly, we found evidence that the proteasome-ubiquitin system is under selection specific to lineages where longevity increased and suggest that its selection had a role in the evolution of longevity. These results provide evidence that natural selection acts on species when longevity evolves, give insights into adaptive genetic changes associated with the evolution of longevity in mammals, and provide evidence that at least some repair systems are selected for when longevity increases.

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Section: Discussionmentioning

confidence: 99%

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Magalhães

2011

AGE

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“…Protein sequences from genes predicted by Maker were functionally annotated using NCBI blastp v.2.2.30+ versus the NCBI non-redundant refseq protein database (http://www.ncbi.nlm.nih.gov/refseq/), versus the UniProt database 48 , and using InterProScan (v. 5.6-48.0) 49 .…”

Section: Methodsmentioning

confidence: 99%

Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum

VanBuren

Bryant

Edger

et al. 2015

Nature

288

271

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Plant genomes, and eukaryotic genomes in general, are typically repetitive, polyploid and heterozygous, which complicates genome assembly 1 . The short read lengths of early Sanger and current next-generation sequencing platforms hinder assembly through complex repeat regions, and many draft and reference genomes are fragmented, lacking skewed GC and repetitive intergenic sequences, which are gaining importance due to projects like the Encyclopedia of DNA Elements (ENCODE) 2 . Here we report the whole-genome sequencing and assembly of the desiccationtolerant grass Oropetium thomaeum. Using only single-molecule real-time sequencing, which generates long (>16 kilobases) reads with random errors, we assembled 99% (244 megabases) of the Oropetium genome into 625 contigs with an N50 length of 2.4 megabases. Oropetium is an example of a 'near-complete' draft genome which includes gapless coverage over gene space as well as intergenic sequences such as centromeres, telomeres, transposable elements and rRNA clusters that are typically unassembled in draft genomes. Oropetium has 28,466 protein-coding genes and 43% repeat sequences, yet with 30% more compact euchromatic regions it is the smallest known grass genome. The Oropetium genome demonstrates the utility of single-molecule real-time sequencing for assembling high-quality plant and other eukaryotic genomes, and serves as a valuable resource for the plant comparative genomics community.The genomes of Arabidopsis 3 , rice 4 , poplar, grape and Sorghum 5 were first sequenced using high-quality and reiterative Sanger-based approaches producing a series of 'gold standard' reference genomes. The advent of next-generation sequencing (NGS) technologies reduced costs of sequencing substantially, which has enabled sequencing of over 100 plant genomes 1 . The quality of plant genome assemblies depends on genome size, ploidy, heterozygosity and sequence coverage, but most NGS-based genomes have on the order of tens of thousands of short contigs distributed in thousands of scaffolds. The short read lengths of NGS, inherent biases and non-random sequencing errors have resulted in highly fragmented draft genome assemblies that are not complete, which means they are missing biologically meaningful sequences including entire genes, regulatory regions, transposable elements, centromeres, telomeres and haplotype-specific structural variations. It is becoming clear from ENCODE projects that complete genomes are needed to better understand the importance of the non-coding regions of genomes 2 .More than 40% of calories consumed by humans are derived from grasses, and the grass family (Poaceae) is arguably the most important plant family with regard to global food security 6 . The size and complexity of most grass genomes has challenged progress in gene discovery and comparative genomics, although draft genomes are now available for most agriculturally important grasses 1 . The largest genome assemblies, such as maize (2,300 megabases (Mb)) 7 , barley (5,100 Mb) 8 and wheat (hexaploid, 1...

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“…The amino-acidic sequences of human TRKA ( 26 ). Their kinase domains were aligned using the MUSCLE tool ( 27 ) and results were post-processed using Jalview ( 28 ).…”

Section: Kinase Domain Alignmentmentioning

confidence: 99%

Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer

Russo

Misale

Ge³

et al. 2016

Cancer Discovery

267

272

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Entrectinib is a fi rst-in-class pan-TRK kinase inhibitor currently undergoing clinical testing in colorectal cancer and other tumor types. A patient with metastatic colorectal cancer harboring an LMNA-NTRK1 rearrangement displayed a remarkable response to treatment with entrectinib, which was followed by the emergence of resistance. To characterize the molecular bases of the patient's relapse, circulating tumor DNA (ctDNA) was collected longitudinally during treatment, and a tissue biopsy, obtained before entrectinib treatment, was transplanted in mice (xenopatient), which then received the same entrectinib regimen until resistance developed. Genetic profi ling of ctDNA and xenopatient samples showed acquisition of two point mutations in the catalytic domain of NTRK1 , p.G595R and p.G667C. Biochemical and pharmacologic analysis in multiple preclinical models confi rmed that either mutation renders the TRKA kinase insensitive to entrectinib. These fi ndings can be immediately exploited to design next-generation TRKA inhibitors. SIGNIFICANCE:We provide proof of principle that analyses of xenopatients (avatar) and liquid biopsies allow the identifi cation of drug resistance mechanisms in parallel with clinical treatment of an individual patient. We describe for the fi rst time that p.G595R and p.G667C TRKA mutations drive acquired resistance to entrectinib in colorectal cancers carrying NTRK1 rearrangements. Cancer Discov; 6(1);[36][37][38][39][40][41][42][43][44]

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The Universal Protein Resource (UniProt): an expanding universe of protein information

Cited by 989 publications

References 22 publications

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity

Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum

Acquired Resistance to the TRK Inhibitor Entrectinib in Colorectal Cancer

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