The neXtProt knowledgebase on human proteins: 2017 update

Gaudet, Pascale; Michel, Pierre-André; Zahn-Zabal, Monique; Britan, Aurore; Cusin, Isabelle; Domagalski, Marcin J.; Duek, Paula D.; Gateau, Alain; Gleizes, Anne; Hinard, Valérie; Laval, Valentine Rech de; Lin, Jinjin; Nikitin, Frédéric; Schaeffer, Mathieu; Teixeira, Daniel; Lane, Lydie; Bairoch, Amos Marc

doi:10.1093/nar/gkw1062

Cited by 148 publications

(155 citation statements)

References 25 publications

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“…Although dystonia appeared to be mostly independent of l ‐dopa intake, dyskinesias were most commonly reported to be treatment‐induced. Another commonly held notion and well‐known clinical observation in the context of recessive PD is its slow(er) progression compared with idiopathic PD . In this context, one should note that we were unable to extract data on disease progression from the available literature, as it is reported in an entirely nonsystematic and unquantified fashion.…”

Section: Discussionmentioning

confidence: 95%

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

et al. 2018

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This first comprehensive MDSGene review is devoted to the 3 autosomal recessive Parkinson's disease forms: PARK-Parkin, PARK-PINK1, and PARK-DJ1. It followed MDSGene's standardized data extraction protocol and screened a total of 3652 citations and is based on fully curated phenotypic and genotypic data on >1100 patients with recessively inherited PD because of 221 different disease-causing mutations in Parkin, PINK1, or DJ1. All these data are also available in an easily searchable online database (www.mdsgene.org), which also provides descriptive summary statistics on phenotypic and genetic data. Despite the high degree of missingness of phenotypic features and unsystematic reporting of genotype data in the original literature, the present review recapitulates many of the previously described findings including early onset (median age at onset of ∼30 years for carriers of at least 2 mutations in any of the 3 genes) of an overall clinically typical form of PD with excellent treatment response, dystonia and dyskinesia being relatively common and cognitive decline relatively uncommon. However, when comparing actual data with common expert knowledge in previously published reviews, we detected several discrepancies. We conclude that systematic reporting of phenotypes is a pressing need in light of increasingly available molecular genetic testing and the emergence of first gene-specific therapies entering clinical trials. © 2018 International Parkinson and Movement Disorder Society.

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Section: Discussionmentioning

confidence: 95%

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

et al. 2018

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“…21 Thus, even within the centromere, histone H3 nucleosomes outnumber CENP-A nucleosomes by approximately 25:1, which means that HyCCAPP likely pulls down many more histone H3 than CENP-A nucleosomes (indeed, histone H3 was detected in all three alpha satellite and scrambled capture samples). On top of this, we must consider that histones are often decorated with a number of post-translational modifications, and indeed a search of CENP-A in the neXtProt database 40 reveals a number of annotated PTMs. The presence of multiple post-translationally modified forms of a base peptide sequence serves to “dilute” the signal of that peptide, thereby lowering the signal-to-noise ratio and making the peptide more difficult to detect.…”

Section: Resultsmentioning

confidence: 99%

Elucidating Protein–DNA Interactions in Human Alphoid Chromatin via Hybridization Capture and Mass Spectrometry

Buxton¹,

Kennedy‐Darling²,

Shortreed³

et al. 2017

J. Proteome Res.

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The centromere is the chromosomal locus where the kinetochore forms and is critical for ensuring proper segregation of sister chromatids during cell division. A substantial amount of effort has been devoted to understanding the characteristic features and roles of the centromere, yet some fundamental aspects of the centromere, such as the complete list of elements that define it, remain obscure. It is well-known that human centromeres include a highly repetitive class of DNA known as alpha satellite, or alphoid, DNA. We present here the first DNA-centric examination of human protein-alpha satellite interactions, employing an approach known as HyCCAPP (hybridization capture of chromatin-associated proteins for proteomics) to identify the protein components of alphoid chromatin in a human cell line. Using HyCCAPP, cross-linked alpha satellite chromatin was isolated from cell lysate, and captured proteins were analyzed via mass spectrometry. After being compared to proteins identified in control pulldown experiments, 90 proteins were identified as enriched at alphoid DNA. This list included many known centromere-binding proteins in addition to multiple novel alpha satellite-binding proteins, such as LRIF1, a heterochromatin-associated protein. The ability of HyCCAPP to reveal both known as well as novel alphoid DNA-interacting proteins highlights the validity and utility of this approach.

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“…This is why these have (almost) the same count (the residual differences being due to synchronisation timings) 13 . The next three sources are also coupled in the sense that not only are GENECODE and Vega marked-up in Ensembl, but there are plans to merge the three.…”

Section: Current Countsmentioning

confidence: 93%

Last rolls of the yoyo: Assessing the human canonical protein count

Southan

2017

F1000Res

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In 2004, when the protein estimate from the finished human genome was only 24,000, the surprise was compounded as reviewed estimates fell to 19,000 by 2014. However, variability in the total canonical protein counts (i.e. excluding alternative splice forms) of open reading frames (ORFs) in different annotation portals persists. This work assesses these differences and possible causes. A 16-year analysis of Ensembl and UniProtKB/Swiss-Prot shows convergence to a protein number of ~20,000. The former had shown some yo-yoing, but both have now plateaued. Nine major annotation portals, reviewed at the beginning of 2017, gave a spread of counts from 21,819 down to 18,891. The 4-way cross-reference concordance (within UniProt) between Ensembl, Swiss-Prot, Entrez Gene and the Human Gene Nomenclature Committee (HGNC) drops to 18,690, indicating methodological differences in protein definitions and experimental existence support between sources. The Swiss-Prot and neXtProt evidence criteria include mass spectrometry peptide verification and also cross-references for antibody detection from the Human Protein Atlas. Notwithstanding, hundreds of Swiss-Prot entries are classified as non-coding biotypes by HGNC. The only inference that protein numbers might still rise comes from numerous reports of small ORF (smORF) discovery. However, while there have been recent cases of protein verifications from previous miss-annotation of non-coding RNA, very few have passed the Swiss-Prot curation and genome annotation thresholds. The post-genomic era has seen both advances in data generation and improvements in the human reference assembly. Notwithstanding, current numbers, while persistently discordant, show that the earlier yo-yoing has largely ceased. Given the importance to biology and biomedicine of defining the canonical human proteome, the task will need more collaborative inter-source curation combined with broader and deeper experimental confirmation in vivo and in vitro of proteins predicted in silico. The eventual closure could be well be below ~19,000.

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The neXtProt knowledgebase on human proteins: 2017 update

Cited by 148 publications

References 25 publications

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

Genotype‐Phenotype Relations for the Parkinson's Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review

Elucidating Protein–DNA Interactions in Human Alphoid Chromatin via Hybridization Capture and Mass Spectrometry

Last rolls of the yoyo: Assessing the human canonical protein count

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