The Dark Proteome Database

Perdigão, Nelson; Rosa, Agostinho; O’Donoghue, Seán I.

doi:10.1186/s13040-017-0144-6

Cited by 18 publications

(42 citation statements)

References 13 publications

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“…The focus of this study however, was the Homo Sapiens and other model organisms where it can be concluded that the amount of dark proteome present in them is still high, whereas in higher eukaryotes like mouse and human, it is around 50%. The results presented above are consistent with previous works (6,23), since Arabidopsis dark proteins are mainly located in extracellular space, cellular membrane and endoplasmic reticulum membranes. C. Elegans dark proteins are present again in cell membrane where they are secreted.…”

Section: Discussionsupporting

confidence: 93%

“…Concerning functions, the results confirmed that dark proteins perform a wide spectrum of functions depending on the organism in question, being more focused in simpler organisms and wider in higher organisms (6). Again, it was sound that a vast amount of then is programmed to live outside the cell, where many are associated with secretion (through secretory glands and guts) or with extracellular areas in tissues, being an indicator that they possibly are designed for being defensive agents against external threats such as bacteria and/or virus.…”

Section: Discussionsupporting

confidence: 56%

“…Annotation Enrichment: The functional analysis by comparing annotations between dark and nondark proteins in a reliable manner, by application of annotation enrichment for the 'Description' (DE) field, where now extended for the 'Features' (FT) field of the Swiss-Prot proteins through Fisher exact tests (11,12) followed by the Benjamini-Hochberg false discovery correction (13,6) with α, the fraction of false positives considered acceptable, set to 1%, and accepting only annotations with an adjusted p value of ≤ 1%, calculated via: where p is from Fisher's test, n is the total of number of annotations in the set, and k is the rank of the largest p-value that satisfies the false discovery criteria as in (6). This approach was then repeatedly applied to compare dark and non-dark proteins across various sets of organisms.…”

Section: Methodsmentioning

confidence: 99%

“…However, there is a dark side of the proteome which we were the first to categorize (5), i.e., regions of protein sequence, or whole sequences, that remain stubbornly inaccessible to either experimental structure determination or modelling approaches such as Aquaria and others. However, this knowledge was updated and is kept in the Dark Proteome Database (DPD) (6) completely independent from Aquaria (4) since our initial work where we had coined the term Dark Proteome (5) as a synonym for the structurally unknown part of the protein sequence universe, i.e., full sequences and/or regions of sequences for which structure is currently undetermined (5,6). After another definition for Dark Proteome appeared as a synonym of intrinsically disordered proteins (IDP) and/or regions (IDR) (7) narrowing the dark proteome definition down to the intrinsically unstructured proteins and/or regions, where their structure determination by conventional methods such as X-ray, Nuclear Magnetic Resonance (NMR) crystallography and Electron Microscopy (EM) are arduous, due to the failure of homology methods, but most important due to their restless nature.…”

Section: Introductionmentioning

confidence: 99%

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Dark Proteome Database: Studies on Dark Proteins

Perdigão¹

2019

Preprint

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The dark proteome as we define it, is the part of the proteome where 3D structure has not been observed either by homology modeling or by experimental characterization in the protein universe. From the 550.116 proteins available in Swiss-Prot (as of July 2016) 43.2% of the Eukarya universe and 49.2% of the Virus universe are part of the dark proteome. In Bacteria and Archaea, the percentage of the dark proteome presence is significantly less, with 12.6% and 13.3% respectively. In this work, we present the map of the dark proteome in Human and in other model organisms. The most significant result is that around 40%-50% of the proteome of these organisms are still in the dark, where the higher percentages belong to higher eukaryotes (mouse and human organisms). Due to the amount of darkness present in the human organism being more than 50%, deeper studies were made, including the identification of 'dark' genes that are responsible for the production of the so-called dark proteins, as well as, the identification of the 'dark' organs where dark proteins are over represented, namely heart, cervical mucosa and natural killer cells. This is a step forward in the direction of the human dark proteome.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dark Proteome Database: Studies on Dark Proteins

Perdigão¹

2019

Preprint

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“…According to the Protein Structure group, the dark proteome consists of proteins for which the experimental structure has never been determined and which are inaccessible to homology modeling. More than half of dark proteins are not intrinsic disorder proteins, have no transmembrane domain, and have a low compositional bias, as shown by Perdigão et al 35,36 .…”

Section: Resultsmentioning

confidence: 91%

Deciphering the Dark Proteome: Use of the Testis and Characterization of Two Dark Proteins

Melaine

Com

Bellaud³

et al. 2018

J. Proteome Res.

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For the C-HPP consortium, dark proteins include not only uPE1, but also missing proteins (MPs, PE2-4), smORFs, proteins from lncRNAs, and products from uncharacterized transcripts. Here, we investigated the expression of dark proteins in the human testis by combining public mRNA and protein expression data for several tissues and performing LC-MS/MS analysis of testis protein extracts. Most uncharacterized proteins are highly expressed in the testis. Thirty could be identified in our data set, of which two were selected for further analyses: (1) A0AOU1RQG5, a putative cancer/testis antigen specifically expressed in the testis, where it accumulates in the cytoplasm of elongated spermatids; and (2) PNMA6E, which is enriched in the testis, where it is found in the germ cell nuclei during most stages of spermatogenesis. Both proteins are coded on Chromosome X. Finally, we studied the expression of other dark proteins, uPE1 and MPs, in a series of human tissues. Most were highly expressed in the testis at both the mRNA and protein levels. The testis appears to be a relevant organ to study the dark proteome, which may have a function related to spermatogenesis and germ cell differentiation. The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD009598.

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Intrinsically Disordered Proteins: The Dark Horse of the Dark Proteome

Kulkarni

Uversky

2018

Proteomics

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A good portion of the 'protein universe' embodies the 'dark proteome'. The latter comprises proteins not amenable to experimental structure determination by existing means and inaccessible to homology modeling. Hence, the dark proteome has remained largely unappreciated. Intrinsically disordered proteins (IDPs) that lack rigid 3D structure are a major component of this dark proteome across all three kingdoms of life. Despite lack of structure, IDPs play critical roles in numerous important biological processes. Furthermore, IDPs serve as crucial constituents of proteinaceous membrane-less organelles (PMLOs), where they often serve as drivers and controllers of biological liquid-liquid phase transitions responsible for the PMLO biogenesis. In this perspective, the role of IDPs is discussed in i) the origin of prebiotic life and the evolution of the first independent primordial living unit akin to Tibor Gánti's chemoton, which preceded the Last Universal Common Ancestor (LUCA), ii) role in multicellularity and hence, in major evolutionary transitions, and iii), their role in phenotypic switching, and the emergence of new traits and adaptive opportunities via non-genetic, protein-based mechanisms. The emerging picture suggests that despite being major constituents of the dark matter, IDPs may be the dark horse in the protein universe.

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The Dark Proteome Database

Cited by 18 publications

References 13 publications

Dark Proteome Database: Studies on Dark Proteins

Dark Proteome Database: Studies on Dark Proteins

Deciphering the Dark Proteome: Use of the Testis and Characterization of Two Dark Proteins

Intrinsically Disordered Proteins: The Dark Horse of the Dark Proteome

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