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PLoS One. 2016 Apr 6;11(4):e0152731. doi: 10.1371/journal.pone.0152731. eCollection 2016.

The Functional Human C-Terminome.

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Nevada Institute of Personalized Medicine, and School of Life Sciences, University of Nevada, Las Vegas, Nevada, United States of America.
Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut 06269-2155, United States of America.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, United States of America.


All translated proteins end with a carboxylic acid commonly called the C-terminus. Many short functional sequences (minimotifs) are located on or immediately proximal to the C-terminus. However, information about the function of protein C-termini has not been consolidated into a single source. Here, we built a new "C-terminome" database and web system focused on human proteins. Approximately 3,600 C-termini in the human proteome have a minimotif with an established molecular function. To help evaluate the function of the remaining C-termini in the human proteome, we inferred minimotifs identified by experimentation in rodent cells, predicted minimotifs based upon consensus sequence matches, and predicted novel highly repetitive sequences in C-termini. Predictions can be ranked by enrichment scores or Gene Evolutionary Rate Profiling (GERP) scores, a measurement of evolutionary constraint. By searching for new anchored sequences on the last 10 amino acids of proteins in the human proteome with lengths between 3-10 residues and up to 5 degenerate positions in the consensus sequences, we have identified new consensus sequences that predict instances in the majority of human genes. All of this information is consolidated into a database that can be accessed through a C-terminome web system with search and browse functions for minimotifs and human proteins. A known consensus sequence-based predicted function is assigned to nearly half the proteins in the human proteome. Weblink:

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