Abundance and Distributions of Eukaryote Protein Simple Sequences

Abstract

Protein simple sequences are a subclass of low complexity regions of sequence that are highly enriched in one or a few residue types. Such sequences are common in transcription regulatory proteins, in structural proteins, in proteins involved in nucleic acid interactions, and in mediating protein-protein interactions. Simple sequences of 10 or more residues, containing >50% of a single residue type are surveyed in this work. Both eukaryote and prokaryote proteomes are investigated with emphasis on the eukaryotes. Very large numbers of such sequences are found in all organisms surveyed. It is found that eukaryotes possess far more simple sequences per protein than do the prokaryotes. Prokaryotes display a linear relationship between number of proteins containing simple sequences and proteome size, whereas it is not clear that such a relationship holds for eukaryotes. Strikingly, it is found that each eukaryote possesses its own unique distribution of simple sequences. Within those distributions it is found that simple sequences enriched in certain residue types are clearly favored, whereas others are just as clearly discriminated against. The preferences observed are not correlated with residue occurrence. An analysis of classes of proteins of known function suggests that simple sequence occurrence and distribution may be related to protein function. Based upon this analysis, the large number of simple sequences found above that would be expected from a simple statistical model, plus the known functional importance of numerous such sequences, it is postulated that eukaryotes have evolved to not only tolerate large numbers of simple sequences but also to require them.

Minimal Plus-end Tracking Unit of the Cytoplasmic Linker Protein CLIP-170

“…Serine-rich regions are present in most CAP-Gly proteins and have been proposed to be linkers between the different domains of the protein, sites of regulation by phosphorylation, or additional tubulin binding domains (28,34,41). In the CLIP family of proteins, these regions are poorly conserved at the primary sequence level and have characteristics of unstructured sequences (34).…”

ATP-dependent Proteases Differ Substantially in Their Ability to Unfold Globular Proteins

“…4, c-f). Such simple sequences are common in both eukaryotic and prokaryotic genomes (113), and it will be interesting to determine how they affect protein homeostasis. It has been shown that simple sequences play an important role in the regulation of two eukaryotic transcription factors by leading to their partial degradation by the proteasome (40).…”

Composition-Modified Matrices Improve Identification of Homologs of Saccharomyces cerevisiae Low-Complexity Glycoproteins

“…Thus, there are about 320,000 low-complexity sequences that cannot be accurately compared or aligned and therefore cannot be compared on any large scale, either functionally or evolutionarily. In addition, there are low-complexity segments in half of all proteins (32). These segments also cannot be reliably aligned and so are currently "masked" by SEG or similar procedures and then ignored by the alignment tools (29,34).…”

“…These proteins are rich in a few amino acids and thus have overall composition significantly different from the "average" compositions seen in the multiple alignments used to construct the BLOSUM alignment scoring matrices and for the BLAST statistical analyses (16). About 10% of known protein sequences have overall low complexity; eukaryotic genomes and some bacterial pathogens contain even higher percentages of lowcomplexity sequences (24,32). The NCBI nonredundant database currently contains approximately 3.2 million sequences.…”