Dark Proteome Database: Studies on Dark Proteins

Abstract

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, at 12.6% and 13.3% respectively. In this work, we present a necessary step to complete the dark proteome picture by introducing the map of the dark proteome in the human and in other model organisms of special importance to mankind. The most significant result is that around 40% to 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 so-called dark proteins, as well as the identification of the ‘dark’ tissues where dark proteins are over represented, namely, the heart, cervical mucosa, and natural killer cells. This is a step forward in the direction of gaining a deeper knowledge of the human dark proteome.

The Active Site of the Enzyme 10-Formyl-THFDH in the Honey Bee Apis mellifera—A Key Player in Formic Acid Detoxification

“…This cannot be correctly predicted, as AlphaFold2 is unable to include co-factor binding in its prediction (Figure 3B). Additionally, the "dark proteome", which is estimated to comprise 44-54% of all proteins in eukaryotic cells, consists of proteins that are unstably folded and, therefore, have no well-defined threedimensional structure [44,45]. Such proteins are thought to play a role in defense or signal transduction and change their structure when interacting with different macromolecules such as RNA and other proteins.…”

Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet

“…Intrinsically-disordered proteins and regions are complicated, as they do not have unique and simple characteristics. Hence, IDPs represent complete disordered proteins that stay disordered, but they can also adopt one conformation when they bind to their ligands or partners [66,67] or participate in multiple systems [68], they are essential to functions [69,70], drug design [71], and protein design [72].…”

The impact of AlphaFold2 on experimental structure solution

“…The "dark proteome" is comprised of proteins with no stable fold that represents a well-dened three-dimensional structure, an estimated 44% of proteins in eukaryotes and viruses. 27,28 These are predominantly intrinsically disordered proteins which are thought to contribute to defence and signalling, sometimes becoming ordered when interacting with other macromolecules. As we have very little data about these proteins in a structural sense, besides their sequence, their structures as well as function cannot (yet) be modelled by machine learning.…”